PEDF Is Associated with the Termination of Chondrocyte Phenotype and Catabolism of Cartilage Tissue.

PubMed

Klinger, P; Lukassen, S; Ferrazzi, F; Ekici, A B; Hotfiel, T; Swoboda, B; Aigner, T; Gelse, K

2017-01-01

Objective. To investigate the expression and target genes of pigment epithelium-derived factor (PEDF) in cartilage and chondrocytes, respectively. Methods. We analyzed the expression pattern of PEDF in different human cartilaginous tissues including articular cartilage, osteophytic cartilage, and fetal epiphyseal and growth plate cartilage, by immunohistochemistry and quantitative real-time (qRT) PCR. Transcriptome analysis after stimulation of human articular chondrocytes with rhPEDF was performed by RNA sequencing (RNA-Seq) and confirmed by qRT-PCR. Results. Immunohistochemically, PEDF could be detected in transient cartilaginous tissue that is prone to undergo endochondral ossification, including epiphyseal cartilage, growth plate cartilage, and osteophytic cartilage. In contrast, PEDF was hardly detected in healthy articular cartilage and in the superficial zone of epiphyses, regions that are characterized by a permanent stable chondrocyte phenotype. RNA-Seq analysis and qRT-PCR demonstrated that rhPEDF significantly induced the expression of a number of matrix-degrading factors including SAA1, MMP1, MMP3, and MMP13. Simultaneously, a number of cartilage-specific genes including COL2A1, COL9A2, COMP, and LECT were among the most significantly downregulated genes. Conclusions. PEDF represents a marker for transient cartilage during all neonatal and postnatal developmental stages and promotes the termination of cartilage tissue by upregulation of matrix-degrading factors and downregulation of cartilage-specific genes. These data provide the basis for novel strategies to stabilize the phenotype of articular cartilage and prevent its degradation.

The Use of an Intra-Articular Depth Guide in the Measurement of Partial Thickness Rotator Cuff Tears

PubMed Central

Carroll, Michael J.; More, Kristie D.; Sohmer, Stephen; Nelson, Atiba A.; Sciore, Paul; Boorman, Richard; Hollinshead, Robert; Lo, Ian K. Y.

2013-01-01

Purpose. The purpose of this study was to compare the accuracy of the conventional method for determining the percentage of partial thickness rotator cuff tears to a method using an intra-articular depth guide. The clinical utility of the intra-articular depth guide was also examined. Methods. Partial rotator cuff tears were created in cadaveric shoulders. Exposed footprint, total tendon thickness, and percentage of tendon thickness torn were determined using both techniques. The results from the conventional and intra-articular depth guide methods were correlated with the true anatomic measurements. Thirty-two patients were evaluated in the clinical study. Results. Estimates of total tendon thickness (r = 0.41, P = 0.31) or percentage of thickness tears (r = 0.67, P = 0.07) using the conventional method did not correlate well with true tendon thickness. Using the intra-articular depth guide, estimates of exposed footprint (r = 0.92, P = 0.001), total tendon thickness (r = 0.96, P = 0.0001), and percentage of tendon thickness torn (r = 0.88, P = 0.004) correlated with true anatomic measurements. Seven of 32 patients had their treatment plan altered based on the measurements made by the intra-articular depth guide. Conclusions. The intra-articular depth guide appeared to better correlate with true anatomic measurements. It may be useful during the evaluation and development of treatment plans for partial thickness articular surface rotator cuff tears. PMID:23533789

Cell therapy in joint disorders.

PubMed

Counsel, Peter D; Bates, Daniel; Boyd, Richard; Connell, David A

2015-01-01

Articular cartilage possesses poor natural healing mechanisms, and a variety of non-cell-based and cell-based treatments aim to promote regeneration of hyaline cartilage. A review of the literature to December 2013 using PubMed with search criteria including the keywords stem cell, cell therapy, cell transplantation, cartilage, chondral, and chondrogenic. Forty-five articles were identified that employed local mesenchymal stem cell (MSC) therapy for joint disorders in humans. Nine comparative studies were identified, consisting of 3 randomized trials, 5 cohort studies, and 1 case-control study. Clinical review. Level 4. Studies were assessed for stem cell source, method of implantation, comparison groups, and concurrent surgical techniques. Two studies comparing MSC treatment to autologous chondrocyte implantation found similar efficacy. Three studies reported clinical benefits with intra-articular MSC injection over non-MSC controls for cases undergoing debridement with or without marrow stimulation, although a randomized study found no significant clinical difference at 2-year follow-up but reported better 18-month magnetic resonance imaging and histologic scores in the MSC group. No human studies have compared intra-articular MSC therapy to non-MSC techniques for osteoarthritis in the absence of surgery. Mesenchymal stem cell-based therapies appear safe and effective for joint disorders in large animal preclinical models. Evidence for use in humans, particularly, comparison with more established treatments such as autologous chondrocyte implantation and microfracture, is limited.

The effects of exercise on human articular cartilage

PubMed Central

Eckstein, F; Hudelmaier, M; Putz, R

2006-01-01

The effects of exercise on articular hyaline articular cartilage have traditionally been examined in animal models, but until recently little information has been available on human cartilage. Magnetic resonance imaging now permits cartilage morphology and composition to be analysed quantitatively in vivo. This review briefly describes the methodological background of quantitative cartilage imaging and summarizes work on short-term (deformational behaviour) and long-term (functional adaptation) effects of exercise on human articular cartilage. Current findings suggest that human cartilage deforms very little in vivo during physiological activities and recovers from deformation within 90 min after loading. Whereas cartilage deformation appears to become less with increasing age, sex and physical training status do not seem to affect in vivo deformational behaviour. There is now good evidence that cartilage undergoes some type of atrophy (thinning) under reduced loading conditions, such as with postoperative immobilization and paraplegia. However, increased loading (as encountered by elite athletes) does not appear to be associated with increased average cartilage thickness. Findings in twins, however, suggest a strong genetic contribution to cartilage morphology. Potential reasons for the inability of cartilage to adapt to mechanical stimuli include a lack of evolutionary pressure and a decoupling of mechanical competence and tissue mass. PMID:16637874

The effects of exercise on human articular cartilage.

PubMed

Eckstein, F; Hudelmaier, M; Putz, R

2006-04-01

The effects of exercise on articular hyaline articular cartilage have traditionally been examined in animal models, but until recently little information has been available on human cartilage. Magnetic resonance imaging now permits cartilage morphology and composition to be analysed quantitatively in vivo. This review briefly describes the methodological background of quantitative cartilage imaging and summarizes work on short-term (deformational behaviour) and long-term (functional adaptation) effects of exercise on human articular cartilage. Current findings suggest that human cartilage deforms very little in vivo during physiological activities and recovers from deformation within 90 min after loading. Whereas cartilage deformation appears to become less with increasing age, sex and physical training status do not seem to affect in vivo deformational behaviour. There is now good evidence that cartilage undergoes some type of atrophy (thinning) under reduced loading conditions, such as with postoperative immobilization and paraplegia. However, increased loading (as encountered by elite athletes) does not appear to be associated with increased average cartilage thickness. Findings in twins, however, suggest a strong genetic contribution to cartilage morphology. Potential reasons for the inability of cartilage to adapt to mechanical stimuli include a lack of evolutionary pressure and a decoupling of mechanical competence and tissue mass.

Computed tomography arthrography with traction in the human hip for three-dimensional reconstruction of cartilage and the acetabular labrum

PubMed Central

Henak, C.R.; Abraham, C.L.; Peters, C.L.; Sanders, R.K.; Weiss, J.A.; Anderson, A.E.

2014-01-01

AIM To develop and demonstrate the efficacy of a computed tomography arthrography (CTA) protocol for the hip that enables accurate three-dimensional reconstructions of cartilage and excellent visualization of the acetabular labrum. MATERIALS AND METHODS Ninety-three subjects were imaged (104 scans); 68 subjects with abnormal anatomy, 11 patients after periacetabular osteotomy surgery, and 25 subjects with normal anatomy. Fifteen to 25 ml of contrast agent diluted with lidocaine was injected using a lateral oblique approach. A Hare traction splint applied traction during CT. The association between traction force and intra-articular joint space was assessed qualitatively under fluoroscopy. Cartilage geometry was reconstructed from the CTA images for 30 subjects; the maximum joint space under traction was measured. RESULTS Using the Hare traction splint, the intra-articular space and boundaries of cartilage could be clearly delineated throughout the joint; the acetabular labrum was also visible. Dysplastic hips required less traction (~5 kg) than normal and retroverted hips required (>10 kg) to separate the cartilage. An increase in traction force produced a corresponding widening of the intra-articular joint space. Under traction, the maximum width of the intra-articular joint space during CT ranged from 0.98–6.7 mm (2.46 ± 1.16 mm). CONCLUSIONS When applied to subjects with normal and abnormal hip anatomy, the CTA protocol presented yields clear delineation of the cartilage and the acetabular labrum. Use of a Hare traction splint provides a simple, cost-effective method to widen the intra-articular joint space during CT, and provides flexibility to vary the traction as required. PMID:25070373

Immunohistochemical study of extracellular matrices and elastic fibers in a human sternoclavicular joint.

PubMed

Shimada, K; Takeshige, N; Moriyama, H; Miyauchi, Y; Shimada, S; Fujimaki, E

1997-12-01

In this study, we clarified the distribution of elastic and oxytalan fibers in a human sternoclavicular joint (SCJ) using a color image system and in extracellular matrices using immunoperoxidase staining. Fine elastic fibers (EFs) were scattered in the fibrous layer of the sternoclavicular disk. This articular disk was composed of a collagenous bundle on the sternum side of the articular disk in the SCJ and cellular components including connective tissue on the clavicular side of the articular disk. The thickness of the disk gradually increased from the inferior to superior portion. Collagen fibers type I, III and V and other extracellular matrices (ECMs) were detected in the hypertrophic zone in the clavicular and sternum side of the SCJ and in the connective tissue of the articulatio condylar. On the cervical surface of the articular disk, cellular activity was higher than on the sternum surface.

A Computational/Experimental Platform for Investigating Three-Dimensional Puzzle Solving of Comminuted Articular Fractures

PubMed Central

Thomas, Thaddeus P.; Anderson, Donald D.; Willis, Andrew R.; Liu, Pengcheng; Frank, Matthew C.; Marsh, J. Lawrence; Brown, Thomas D.

2011-01-01

Reconstructing highly comminuted articular fractures poses a difficult surgical challenge, akin to solving a complicated three-dimensional (3D) puzzle. Pre-operative planning using CT is critically important, given the desirability of less invasive surgical approaches. The goal of this work is to advance 3D puzzle solving methods toward use as a pre-operative tool for reconstructing these complex fractures. Methodology for generating typical fragmentation/dispersal patterns was developed. Five identical replicas of human distal tibia anatomy, were machined from blocks of high-density polyetherurethane foam (bone fragmentation surrogate), and were fractured using an instrumented drop tower. Pre- and post-fracture geometries were obtained using laser scans and CT. A semi-automatic virtual reconstruction computer program aligned fragment native (non-fracture) surfaces to a pre-fracture template. The tibias were precisely reconstructed with alignment accuracies ranging from 0.03-0.4mm. This novel technology has potential to significantly enhance surgical techniques for reconstructing comminuted intra-articular fractures, as illustrated for a representative clinical case. PMID:20924863

Secretome analysis of human articular chondrocytes unravels catabolic effects of nicotine on the joint.

PubMed

Lourido, Lucía; Calamia, Valentina; Fernández-Puente, Patricia; Mateos, Jesús; Oreiro, Natividad; Blanco, Francisco J; Ruiz-Romero, Cristina

2016-06-01

Osteoarthritis (OA) is a degenerative joint pathology characterized by articular cartilage degradation that lacks from efficient therapy. Since previous epidemiological data show a high controversy regarding the role of smoking in OA, we aimed to evaluate the effects of nicotine (the most physiologically active compound of tobacco) on the joint. Secretome analyses, based on metabolic labeling followed by LC-MALDI-TOF/TOF analysis, were carried out using an in vitro model of articular inflammation (primary human articular chondrocytes treated with interleukin-1β), and also on osteoarthritic cells. ELISA and Western blot assays were performed to verify some of the results. Nineteen proteins were altered by nicotine in the model of articular inflammation, including several cytokines and proteases. We confirmed the increased secretion by nicotine of matrix metalloproteinase 1 and two proposed markers of OA, fibronectin, and chitinase 3-like protein 1. Finally, four components of the extracellular matrix of cartilage were decreased by nicotine in OA chondrocytes. Our data contribute to a better understanding of the molecular mechanisms that are modulated by nicotine in cartilage cells, suggesting a negative effect of this drug on the joint. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Human mesenchymal stem cell differentiation to NP-like cells in chitosan-glycerophosphate hydrogels.

PubMed

Richardson, Stephen M; Hughes, Nesta; Hunt, John A; Freemont, Anthony J; Hoyland, Judith A

2008-01-01

Intervertebral disc (IVD) degeneration is one of the major causes of low back pain. As current clinical treatments are aimed at restoring biomechanical function and providing symptomatic relief, interest in methods focused on biological repair has increased. Several tissue engineering approaches using different cell types and hydrogels/scaffolds have been proposed. Owing to the unsuitable nature of degenerate cells for tissue engineering attention has focused on the use of mesenchymal stem cells (MSCs). Additionally, while rigid scaffolds have been demonstrated to allow MSC differentiation to the chondrocyte-like cells of the IVD, hydrogels are being increasingly studied as they allow minimally invasive implantation without extensive damage to the IVD. Here, we have studied the temperature-sensitive hydrogel chitosan-glycerophosphate (C/Gp), seeded with human MSCs and cultured for 4 weeks in standard medium. We have analysed the gene and protein expression profile of the MSCs and compared it to that of both nucleus pulposus (NP) cells and articular chondrocytes cultured in C/Gp. Gene expression analysis for chondrocytic-cell marker genes demonstrated differentiation of MSCs to a phenotype which showed similarities to both articular chondrocytes and NP cells. Conventional PCR demonstrated a lack of expression of osteogenic marker genes and the hypertrophic marker gene type X collagen. MSCs also secreted both proteoglycans and collagens in a ratio, which more closely resembled that of NP cells than articular chondrocytes. These results therefore suggest that MSC-seeded C/Gp gels could be used clinically for the regeneration of the degenerate human IVD.

Articular Cartilage Aging-Potential Regenerative Capacities of Cell Manipulation and Stem Cell Therapy

PubMed Central

Placek, Waldemar

2018-01-01

Changes in articular cartilage during the aging process are a stage of natural changes in the human body. Old age is the major risk factor for osteoarthritis but the disease does not have to be an inevitable consequence of aging. Chondrocytes are particularly prone to developing age-related changes. Changes in articular cartilage that take place in the course of aging include the acquisition of the senescence-associated secretory phenotype by chondrocytes, a decrease in the sensitivity of chondrocytes to growth factors, a destructive effect of chronic production of reactive oxygen species and the accumulation of the glycation end products. All of these factors affect the mechanical properties of articular cartilage. A better understanding of the underlying mechanisms in the process of articular cartilage aging may help to create new therapies aimed at slowing or inhibiting age-related modifications of articular cartilage. This paper presents the causes and consequences of cellular aging of chondrocytes and the biological therapeutic outlook for the regeneration of age-related changes of articular cartilage. PMID:29470431

In situ measurements of human articular cartilage stiffness by means of a scanning force microscope

NASA Astrophysics Data System (ADS)

Imer, Raphaël; Akiyama, Terunobu; de Rooij, Nico F.; Stolz, Martin; Aebi, Ueli; Kilger, Robert; Friederich, Niklaus F.; Wirz, Dieter; Daniels, A. U.; Staufer, Urs

2007-03-01

Osteoarthritis is a painful and disabling progressive joint disease, characterized by degradation of articular cartilage. In order to study this disease at early stages, we have miniaturized and integrated a complete scanning force microscope into a standard arthroscopic device fitting through a standard orthopedic canula. This instrument will allow orthopedic surgeons to measure the mechanical properties of articular cartilage at the nanometer and micrometer scale in-vivo during a standard arthroscopy. An orthopedic surgeon assessed the handling of the instrument. First measurements of the elasticity-modulus of human cartilage were recorded in a cadaver knee non minimal invasive. Second, minimally invasive experiments were performed using arthroscopic instruments. Load-displacement curves were successfully recorded.

A Clinically Realistic Large Animal Model of Intra-Articular Fracture

DTIC Science & Technology

2012-10-01

articular bone intact. The distal impact face is anchored to the talus using three “tripod” pins, for direct (i.e., no soft tissue intervention) delivery of...pilon) fractures. In this technique, the porcine hock joint (human ankle analogue) is subjected to an injurious transarticular compressive force pulse...fracture, to create fractures morphologically similar to human ankle anterior malleolar fractures. This cut was made on the anterior distal tibial cortex

ROCK inhibitor prevents the dedifferentiation of human articular chondrocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matsumoto, Emi; Furumatsu, Takayuki, E-mail: matino@md.okayama-u.ac.jp; Kanazawa, Tomoko

2012-03-30

Highlights: Black-Right-Pointing-Pointer ROCK inhibitor stimulates chondrogenic gene expression of articular chondrocytes. Black-Right-Pointing-Pointer ROCK inhibitor prevents the dedifferentiation of monolayer-cultured chondrocytes. Black-Right-Pointing-Pointer ROCK inhibitor enhances the redifferentiation of cultured chondrocytes. Black-Right-Pointing-Pointer ROCK inhibitor is useful for preparation of un-dedifferentiated chondrocytes. Black-Right-Pointing-Pointer ROCK inhibitor may be a useful reagent for chondrocyte-based regeneration therapy. -- Abstract: Chondrocytes lose their chondrocytic phenotypes in vitro. The Rho family GTPase ROCK, involved in organizing the actin cytoskeleton, modulates the differentiation status of chondrocytic cells. However, the optimum method to prepare a large number of un-dedifferentiated chondrocytes is still unclear. In this study, we investigated the effectmore » of ROCK inhibitor (ROCKi) on the chondrogenic property of monolayer-cultured articular chondrocytes. Human articular chondrocytes were subcultured in the presence or absence of ROCKi (Y-27632). The expression of chondrocytic marker genes such as SOX9 and COL2A1 was assessed by quantitative real-time PCR analysis. Cellular morphology and viability were evaluated. Chondrogenic redifferentiation potential was examined by a pellet culture procedure. The expression level of SOX9 and COL2A1 was higher in ROCKi-treated chondrocytes than in untreated cells. Chondrocyte morphology varied from a spreading form to a round shape in a ROCKi-dependent manner. In addition, ROCKi treatment stimulated the proliferation of chondrocytes. The deposition of safranin O-stained proteoglycans and type II collagen was highly detected in chondrogenic pellets derived from ROCKi-pretreated chondrocytes. Our results suggest that ROCKi prevents the dedifferentiation of monolayer-cultured chondrocytes, and may be a useful reagent to maintain chondrocytic phenotypes in vitro for chondrocyte-based regeneration therapy.« less

Estimation of Articular Cartilage Surface Roughness Using Gray-Level Co-Occurrence Matrix of Laser Speckle Image.

PubMed

Youssef, Doaa; El-Ghandoor, Hatem; Kandel, Hamed; El-Azab, Jala; Hassab-Elnaby, Salah

2017-06-28

The application of He-Ne laser technologies for description of articular cartilage degeneration, one of the most common diseases worldwide, is an innovative usage of these technologies used primarily in material engineering. Plain radiography and magnetic resonance imaging are insufficient to allow the early assessment of the disease. As surface roughness of articular cartilage is an important indicator of articular cartilage degeneration progress, a safe and noncontact technique based on laser speckle image to estimate the surface roughness is provided. This speckle image from the articular cartilage surface, when illuminated by laser beam, gives very important information about the physical properties of the surface. An experimental setup using a low power He-Ne laser and a high-resolution digital camera was implemented to obtain speckle images of ten bovine articular cartilage specimens prepared for different average roughness values. Texture analysis method based on gray-level co-occurrence matrix (GLCM) analyzed on the captured speckle images is used to characterize the surface roughness of the specimens depending on the computation of Haralick's texture features. In conclusion, this promising method can accurately estimate the surface roughness of articular cartilage even for early signs of degeneration. The method is effective for estimation of average surface roughness values ranging from 0.09 µm to 2.51 µm with an accuracy of 0.03 µm.

Estimation of Articular Cartilage Surface Roughness Using Gray-Level Co-Occurrence Matrix of Laser Speckle Image

PubMed Central

El-Ghandoor, Hatem; Kandel, Hamed; El-Azab, Jala; Hassab-Elnaby, Salah

2017-01-01

The application of He-Ne laser technologies for description of articular cartilage degeneration, one of the most common diseases worldwide, is an innovative usage of these technologies used primarily in material engineering. Plain radiography and magnetic resonance imaging are insufficient to allow the early assessment of the disease. As surface roughness of articular cartilage is an important indicator of articular cartilage degeneration progress, a safe and noncontact technique based on laser speckle image to estimate the surface roughness is provided. This speckle image from the articular cartilage surface, when illuminated by laser beam, gives very important information about the physical properties of the surface. An experimental setup using a low power He-Ne laser and a high-resolution digital camera was implemented to obtain speckle images of ten bovine articular cartilage specimens prepared for different average roughness values. Texture analysis method based on gray-level co-occurrence matrix (GLCM) analyzed on the captured speckle images is used to characterize the surface roughness of the specimens depending on the computation of Haralick’s texture features. In conclusion, this promising method can accurately estimate the surface roughness of articular cartilage even for early signs of degeneration. The method is effective for estimation of average surface roughness values ranging from 0.09 µm to 2.51 µm with an accuracy of 0.03 µm. PMID:28773080

The Effect of Intra-articular Corticosteroids on Articular Cartilage

PubMed Central

Wernecke, Chloe; Braun, Hillary J.; Dragoo, Jason L.

2015-01-01

Background: Intra-articular (IA) corticosteroid therapy has been used for the treatment of inflammation and pain in the knee since the 1950s. Purpose: To review the current literature on the effects of IA corticosteroids on articular cartilage. Study Design: Systematic review. Methods: A MEDLINE and SCOPUS database search was performed, and studies were selected for basic science and clinical trial research on corticosteroids with direct outcome measures of cartilage health. Preliminary searches yielded 1929 articles, and final analysis includes 40 studies. Results: Methylprednisolone, dexamethasone, hydrocortisone, betamethasone, prednisolone, and triamcinolone were reported to display dose-dependent deleterious effects on cartilage morphology, histology, and viability in both in vitro and in vivo models. The beneficial animal in vivo effects of methylprednisolone, hydrocortisone, and triamcinolone occurred at low doses (usually <2-3 mg/dose or 8-12 mg/cumulative total dose in vivo), at which increased cell growth and recovery from damage was observed; the single human clinical trial indicated a beneficial effect of triamcinolone. However, at higher doses (>3 mg/dose or 18-24 mg/cumulative total dose in vivo), corticosteroids were associated with significant gross cartilage damage and chondrocyte toxicity. Dose and time dependency of corticosteroid chondrotoxicity was supported in the in vitro results, however, without clear dose thresholds. Conclusion: Corticosteroids have a time- and dose-dependent effect on articular cartilage, with beneficial effects occurring at low doses and durations and detrimental effects at high doses and durations. Clinically, beneficial effects are supported for IA administration, but the lowest efficacious dose should be used. PMID:26674652

Molecular changes in articular cartilage and subchondral bone in the rat anterior cruciate ligament transection and meniscectomized models of osteoarthritis

PubMed Central

2011-01-01

Background Osteoarthritis (OA) is a debilitating, progressive joint disease. Methods Similar to the disease progression in humans, sequential events of early cartilage degradation, subchondral osteopenia followed by sclerosis, and late osteophyte formation were demonstrated in the anterior cruciate ligament transection (ACLT) or ACLT with partial medial meniscectomy (ACLT + MMx) rat OA models. We describe a reliable and consistent method to examine the time dependent changes in the gene expression profiles in articular cartilage and subchondral bone. Results Local regulation of matrix degradation markers was demonstrated by a significant increase in mRNA levels of aggrecanase-1 and MMP-13 as early as the first week post-surgery, and expression remained elevated throughout the 10 week study. Immunohistochemistry confirmed MMP-13 expression in differentiated chondrocytes and synovial fibroblasts at week-2 and cells within osteophytes at week-10 in the surgically-modified-joints. Concomitant increases in chondrocyte differentiation markers, Col IIA and Sox 9, and vascular invasion markers, VEGF and CD31, peaked around week-2 to -4, and returned to Sham levels at later time points in both models. Indeed, VEGF-positive cells were found in the deep articular chondrocytes adjacent to subchondral bone. Osteoclastic bone resorption markers, cathepsin K and TRAP, were also elevated at week-2. Confirming bone resorption is an early local event in OA progression, cathepsin K positive osteoclasts were found invading the articular cartilage from the subchondral region at week 2. This was followed by late disease events, including subchondral sclerosis and osteophyte formation, as demonstrated by the upregulation of the osteoanabolic markers runx2 and osterix, toward week-4 to 6 post-surgery. Conclusions In summary, this study demonstrated the temporal and cohesive gene expression changes in articular cartilage and subchondral bone using known markers of OA progression. The findings here support genome-wide profiling efforts to elucidate the sequential and complex regulation of the disease. PMID:21864409

Comparison of MRI-based estimates of articular cartilage contact area in the tibiofemoral joint.

PubMed

Henderson, Christopher E; Higginson, Jill S; Barrance, Peter J

2011-01-01

Knee osteoarthritis (OA) detrimentally impacts the lives of millions of older Americans through pain and decreased functional ability. Unfortunately, the pathomechanics and associated deviations from joint homeostasis that OA patients experience are not well understood. Alterations in mechanical stress in the knee joint may play an essential role in OA; however, existing literature in this area is limited. The purpose of this study was to evaluate the ability of an existing magnetic resonance imaging (MRI)-based modeling method to estimate articular cartilage contact area in vivo. Imaging data of both knees were collected on a single subject with no history of knee pathology at three knee flexion angles. Intra-observer reliability and sensitivity studies were also performed to determine the role of operator-influenced elements of the data processing on the results. The method's articular cartilage contact area estimates were compared with existing contact area estimates in the literature. The method demonstrated an intra-observer reliability of 0.95 when assessed using Pearson's correlation coefficient and was found to be most sensitive to changes in the cartilage tracings on the peripheries of the compartment. The articular cartilage contact area estimates at full extension were similar to those reported in the literature. The relationships between tibiofemoral articular cartilage contact area and knee flexion were also qualitatively and quantitatively similar to those previously reported. The MRI-based knee modeling method was found to have high intra-observer reliability, sensitivity to peripheral articular cartilage tracings, and agreeability with previous investigations when using data from a single healthy adult. Future studies will implement this modeling method to investigate the role that mechanical stress may play in progression of knee OA through estimation of articular cartilage contact area.

Mechanical properties of human articular disk and its influence on TMJ loading studied with the finite element method.

PubMed

Tanaka, E; Sasaki, A; Tahmina, K; Yamaguchi, K; Mori, Y; Tanne, K

2001-03-01

The present study was designed to investigate the elastic modulus of human temporomandibular joint (TMJ) disk under tension and its influences on TMJ loading. Seven human TMJ disks served as specimens. Continuous tensile stress was applied to each specimen, and the elastic moduli of human TMJ disks were calculated at 2% strain. Furthermore, using a three-dimensional finite element model of the mandible including the TMJ, changes in the TMJ stresses during clenching were evaluated in association of varying elastic moduli of the articular disk determined by the tensile tests. The elastic moduli at 2% strain varied from 27.1 to 65.2 MPa with a mean of 47.1 MPa. A significant correlation was found between the elastic moduli and age (P < 0.01). On the surface of condyle, compressive stress in the anterior area and tensile stress in the posterior area increased when the elastic moduli of the TMJ disk was varied from 25 to 65 MPa. In the TMJ disk, shear stresses in all the areas became larger with greater stiffness. In conclusion, it is shown that the elastic modulus of human TMJ disk is increased with age and that higher stiffness of the disk exerts substantial influences on mechanical loading for the TMJ structures.

Safety Studies for Use of Adipose Tissue‐Derived Mesenchymal Stromal/Stem Cells in a Rabbit Model for Osteoarthritis to Support a Phase I Clinical Trial

PubMed Central

Riester, Scott M.; Denbeigh, Janet M.; Lin, Yang; Jones, Dakota L.; de Mooij, Tristan; Lewallen, Eric A.; Nie, Hai; Paradise, Christopher R.; Radel, Darcie J.; Dudakovic, Amel; Camilleri, Emily T.; Larson, Dirk R.; Qu, Wenchun; Krych, Aaron J.; Frick, Matthew A.; Im, Hee‐Jeong; Dietz, Allan B.; Smith, Jay

2016-01-01

Abstract Adipose‐derived mesenchymal stem cells (AMSCs) offer potential as a therapeutic option for clinical applications in musculoskeletal regenerative medicine because of their immunomodulatory functions and capacity for trilineage differentiation. In preparation for a phase I clinical trial using AMSCs to treat patients with osteoarthritis, we carried out preclinical studies to assess the safety of human AMSCs within the intra‐articular joint space. Culture‐expanded human AMSCs grown in human platelet‐lysate were delivered via intra‐articular injections into normal healthy rabbit knees and knees at risk for the development of osteoarthritis after bilateral medial anterior hemimeniscectomy. Treatment outcomes and safety were evaluated by assessing the general health, function, and behavior of the animals. Joint tissues were analyzed by x‐ray, magnetic resonance imaging, and histopathology. Intra‐articular AMSC therapy was well tolerated in this study. We did not observe adverse systemic reactions, nor did we find evidence of damage to intra‐articular joint tissues. Thus, the data generated in this study show a favorable safety profile for AMSCs within the joint space in support of a phase I clinical trial evaluating the clinical utility of AMSCs to treat osteoarthritis. Stem Cells Translational Medicine 2017;6:910–922 PMID:28297568

Magnetically targeted delivery through cartilage

NASA Astrophysics Data System (ADS)

Jafari, Sahar; Mair, Lamar O.; Chowdhury, Sagar; Nacev, Alek; Hilaman, Ryan; Stepanov, Pavel; Baker-McKee, James; Ijanaten, Said; Koudelka, Christian; English, Bradley; Malik, Pulkit; Weinberg, Irving N.

2018-05-01

In this study, we have invented a method of delivering drugs deep into articular cartilage with shaped dynamic magnetic fields acting on small metallic magnetic nanoparticles with polyethylene glycol coating and average diameter of 30 nm. It was shown that transport of magnetic nanoparticles through the entire thickness of bovine articular cartilage can be controlled by a combined alternating magnetic field at 100 Hz frequency and static magnetic field of 0.8 tesla (T) generated by 1" dia. x 2" thick permanent magnet. Magnetic nanoparticles transport through bovine articular cartilage samples was investigated at various settings of magnetic field and time durations. Combined application of an alternating magnetic field and the static field gradient resulted in a nearly 50 times increase in magnetic nanoparticles transport in bovine articular cartilage tissue as compared with static field conditions. This method can be applied to locally deliver therapeutic-loaded magnetic nanoparticles deep into articular cartilage to prevent cartilage degeneration and promote cartilage repair in osteoarthritis.

Locked nailing for the treatment of displaced articular fractures of the calcaneus: description of a new procedure with calcanail(®).

PubMed

Goldzak, Mario; Mittlmeier, Thomas; Simon, Patrick

2012-05-01

Although open reduction and internal fixation is considered the best method for treating displaced articular fractures of the calcaneus, lateral approach is at high risk for wound healing complications. For this reason, the authors developed a posterior approach and a new implant to perform both intrafocal reduction and internal fixation. The aim of this technical note is to describe this method of treatment for displaced articular fractures of the calcaneus, which offered the following advantages: (a) the creation of a working channel that provides also a significant bone autograft, (b) the intrafocal reduction of the displaced articular surface, (c) the insertion of a locking nail that maintains the reduced articular surface at the right height, (d) the possibility to switch from an ORIF to a reconstruction arthrodesis with the same approach and instrumentation in case of severely damaged posterior facet.

Methods and Variables Associated with the Risk of Septic Arthritis Following Intra-Articular Injections in Horses: A Survey of Veterinarians.

PubMed

Gillespie, Caroline C; Adams, Stephen B; Moore, George E

2016-11-01

To determine common methods for intra-articular injections and variables associated with the risk of septic arthritis following intra-articular injection in the horse. Cross-sectional survey. Equine veterinarians. A link to an online survey was distributed to equine practitioners in 2014. Responses for descriptive data were tabulated. Data on infection rates obtained from medical records were analyzed. Variables associated with the risk of septic arthritis were determined using χ 2 or Fisher's exact tests and logistic regression. Common current methods for intra-articular injections were determined from 241 surveys. Sixty-four of 241 surveys (26.6%) contained data with numbers of joints injected and number of infections obtained from review of medical records. Eight different injection methods were used by more than 2/3 of responding veterinarians. A total of 67 out of 319,760 injected joints reported became septic following injection, giving an incidence of 2.10 septic joints per 10,000 intra-articular injections. Based on multivariate analysis, infection rates were significantly lower when veterinarians prepared their own injection sites (OR=0.10) and had <20 years of practice experience (OR=0.025), whereas infection rates were significantly higher when hair was removed at the injection site (OR=19.70). There is a low incidence of septic arthritis following intra-articular injection and a large number of injection methods reported by responding veterinarians. The low reported incidence of infection may be related to the large number of practitioners frequently using common methods. © Copyright 2016 by The American College of Veterinary Surgeons.

The Relationship between MR Parameters and Biomechanical Quantities of Loaded Human Articular Cartilage in Osteoarthritis: An In-Vitro Study

NASA Astrophysics Data System (ADS)

Juráš, V.; Szomolányi, P.; Gäbler, S.; Frollo, I.; Trattnig, S.

2009-01-01

The aim of this study was to assess the changes in MRI parameters during applied load directly in MR scanner and correlate these changes with biomechanical parameters of human articular cartilage. Cartilage explants from patients who underwent total knee replacement were examined in the micro-imaging system in 3T scanner. Respective MRI parameters (T1 without- and T1 with contrast agent as a marker of proteoglycan content, T2 as a marker of collagen network anisotropy and ADC as a measure of diffusivity) were calculated in pre- and during compression state. Subsequently, these parameters were compared to the biomechanical properties of articular cartilage, instantaneous modulus (I), equilibrium modulus (Eq) and time of tissue relaxation (τ). Significant load-induced changes of T2 and ADC were recorded. High correlation between T1Gd and I (r = 0.6324), and between ADC and Eq (r = -0.4884) was found. Multi-parametric MRI may have great potential in analyzing static and dynamic biomechanical behavior of articular cartilage in early stages of osteoarthritis (OA).

Development of methods for analysis of knee articular cartilage degeneration by magnetic resonance imaging data

NASA Astrophysics Data System (ADS)

Suponenkovs, Artjoms; Glazs, Aleksandrs; Platkajis, Ardis

2017-03-01

The aim of this paper is to describe the new methods for analyzing knee articular cartilage degeneration. The most important aspects regarding research about magnetic resonance imaging, knee joint anatomy, stages of knee osteoarthritis, medical image segmentation and relaxation times calculation. This paper proposes new methods for relaxation times calculation and medical image segmentation. The experimental part describes the most important aspect regarding analysing of articular cartilage relaxation times changing. This part contains experimental results, which show the codependence between relaxation times and organic structure. These experimental results and proposed methods can be helpful for early osteoarthritis diagnostics.

A bi-articular model for scapular-humeral rhythm reconstruction through data from wearable sensors.

PubMed

Lorussi, Federico; Carbonaro, Nicola; De Rossi, Danilo; Tognetti, Alessandro

2016-04-23

Patient-specific performance assessment of arm movements in daily life activities is fundamental for neurological rehabilitation therapy. In most applications, the shoulder movement is simplified through a socket-ball joint, neglecting the movement of the scapular-thoracic complex. This may lead to significant errors. We propose an innovative bi-articular model of the human shoulder for estimating the position of the hand in relation to the sternum. The model takes into account both the scapular-toracic and gleno-humeral movements and their ratio governed by the scapular-humeral rhythm, fusing the information of inertial and textile-based strain sensors. To feed the reconstruction algorithm based on the bi-articular model, an ad-hoc sensing shirt was developed. The shirt was equipped with two inertial measurement units (IMUs) and an integrated textile strain sensor. We built the bi-articular model starting from the data obtained in two planar movements (arm abduction and flexion in the sagittal plane) and analysing the error between the reference data - measured through an optical reference system - and the socket-ball approximation of the shoulder. The 3D model was developed by extending the behaviour of the kinematic chain revealed in the planar trajectories through a parameter identification that takes into account the body structure of the subject. The bi-articular model was evaluated in five subjects in comparison with the optical reference system. The errors were computed in terms of distance between the reference position of the trochlea (end-effector) and the correspondent model estimation. The introduced method remarkably improved the estimation of the position of the trochlea (and consequently the estimation of the hand position during reaching activities) reducing position errors from 11.5 cm to 1.8 cm. Thanks to the developed bi-articular model, we demonstrated a reliable estimation of the upper arm kinematics with a minimal sensing system suitable for daily life monitoring of recovery.

A comparative analysis of 7.0-Tesla magnetic resonance imaging and histology measurements of knee articular cartilage in a canine posterolateral knee injury model: a preliminary analysis.

PubMed

Pepin, Scott R; Griffith, Chad J; Wijdicks, Coen A; Goerke, Ute; McNulty, Margaret A; Parker, Josh B; Carlson, Cathy S; Ellermann, Jutta; LaPrade, Robert F

2009-11-01

There has recently been increased interest in the use of 7.0-T magnetic resonance imaging for evaluating articular cartilage degeneration and quantifying the progression of osteoarthritis. The purpose of this study was to evaluate articular cartilage cross-sectional area and maximum thickness in the medial compartment of intact and destabilized canine knees using 7.0-T magnetic resonance images and compare these results with those obtained from the corresponding histologic sections. Controlled laboratory study. Five canines had a surgically created unilateral grade III posterolateral knee injury that was followed for 6 months before euthanasia. The opposite, noninjured knee was used as a control. At necropsy, 3-dimensional gradient echo images of the medial tibial plateau of both knees were obtained using a 7.0-T magnetic resonance imaging scanner. Articular cartilage area and maximum thickness in this site were digitally measured on the magnetic resonance images. The proximal tibias were processed for routine histologic analysis with hematoxylin and eosin staining. Articular cartilage area and maximum thickness were measured in histologic sections corresponding to the sites of the magnetic resonance slices. The magnetic resonance imaging results revealed an increase in articular cartilage area and maximum thickness in surgical knees compared with control knees in all specimens; these changes were significant for both parameters (P <.05 for area; P <.01 for thickness). The average increase in area was 14.8% and the average increase in maximum thickness was 15.1%. The histologic results revealed an average increase in area of 27.4% (P = .05) and an average increase in maximum thickness of 33.0% (P = .06). Correlation analysis between the magnetic resonance imaging and histology data revealed that the area values were significantly correlated (P < .01), but the values for thickness obtained from magnetic resonance imaging were not significantly different from the histology sections (P > .1). These results demonstrate that 7.0-T magnetic resonance imaging provides an alternative method to histology to evaluate early osteoarthritic changes in articular cartilage in a canine model by detecting increases in articular cartilage area. The noninvasive nature of 7.0-T magnetic resonance imaging will allow for in vivo monitoring of osteoarthritis progression and intervention in animal models and humans for osteoarthritis.

Intra Articular Therapeutic Delivery for Post Traumatic Osteoarthritis

DTIC Science & Technology

2016-10-01

method. Our central hypotheses are that joint retention time and therapeutic efficacy will be influenced by amniotic membrane particle size ...three Specific Aims: Aim 1: Evaluate the effects of human amniotic membrane (AM) particle size distribution on particle retention and progression of OA...following trauma. Factors we hypothesized would impact therapeutic efficacy of dHACM included particle size , timing of treatment, and frequency of delivery

Exogenous fibroblast growth factor 9 attenuates cartilage degradation and aggravates osteophyte formation in post-traumatic osteoarthritis.

PubMed

Zhou, S; Wang, Z; Tang, J; Li, W; Huang, J; Xu, W; Luo, F; Xu, M; Wang, J; Wen, X; Chen, L; Chen, H; Su, N; Shen, Y; Du, X; Xie, Y; Chen, L

2016-12-01

The aim of the present study is to investigate the effects of exogenous fibroblast growth factor (FGF)9 on the progression of post-traumatic osteoarthritis (OA). The expression of FGF9 in articular cartilage with OA is detected by immunohistochemistry (IHC). The effects of intra-articular exogenous FGF9 injection on post-traumatic OA induced by the destabilization of the medial meniscus (DMM) surgery are evaluated. Cartilage changes and osteophyte formation in knee joints are investigated by histological analysis. Changes in subchondral bone are evaluated by microcomputed tomography (micro-CT). The effect of exogenous FGF9 on an interleukin-1β (IL-1β)-induced ex vivo OA model of human articular cartilage tissues is also evaluated. FGF9 expression was down-regulated in articular chondrocytes of OA but ectopically induced at sites of osteophyte formation. Intra-articular injection of exogenous FGF9 attenuated articular cartilage degradation in mice after DMM surgery. Exogenous FGF9 suppressed collagen X and MMP13 expressions in OA cartilage, while promoted collagen II expression. Similar results were observed in IL-1β-induced ex vivo OA model. Intra-articular injection of FGF9 had no significant effect on the subchondral bone of knee joints after DMM surgery, but aggravated osteophyte formation. The expressions of SOX9 and collagen II, and cell proliferation were up-regulated at sites of initial osteophyte formation in mice with exogenous FGF9 treatment. Intra-articular injection of exogenous FGF9 delays articular cartilage degradation in post-traumatic OA, while aggravates osteophyte formation. Copyright © 2016. Published by Elsevier Ltd.

Histology of two rice bodies isolated from the stifle of an adult draught horse stallion

PubMed Central

Heimann, Marianne; Lejeune, Jean-Philippe; Verwilghen, Denis R.V.G.; Deby-Dupont, Ginette P.; Serteyn, Didier A.

2006-01-01

In the human and equine species, different kinds of free floating intra-articular particles are related to certain disorders. Osteochondral fragments formed during osteochondrosis dissecans are the most common finding in the equine species, whereas in humans rice bodies due to rheumatoid arthritis are more frequent. Herein we report a third type of floating body inside the stifle of an adult draught horse stallion, in macroscopic appearance similar to articular rice bodies known in humans. As revealed by histologic examination, the two particles consist of polypoid degenerated structures derived from synovial villi. Their formation was probably induced by ischemia. PMID:16434856

Histology of two rice bodies isolated from the stifle of an adult draught horse stallion.

PubMed

Schneider, Nicole; Heimann, Marianne; Lejeune, Jean-Philippe; Verwilghen, Denis R V G; Deby-Dupont, Ginette P; Serteyn, Didier A

2006-03-01

In the human and equine species, different kinds of free floating intra-articular particles are related to certain disorders. Osteochondral fragments formed during osteochondrosis dissecans are the most common finding in the equine species, whereas in humans rice bodies due to rheumatoid arthritis are more frequent. Herein we report a third type of floating body inside the stifle of an adult draught horse stallion, in macroscopic appearance similar to articular rice bodies known in humans. As revealed by histologic examination, the two particles consist of polypoid degenerated structures derived from synovial villi. Their formation was probably induced by ischemia.

Intra-Articular Cellular Therapy for Osteoarthritis and Focal Cartilage Defects of the Knee: A Systematic Review of the Literature and Study Quality Analysis.

PubMed

Chahla, Jorge; Piuzzi, Nicolas S; Mitchell, Justin J; Dean, Chase S; Pascual-Garrido, Cecilia; LaPrade, Robert F; Muschler, George F

2016-09-21

Intra-articular cellular therapy injections constitute an appealing strategy that may modify the intra-articular milieu or regenerate cartilage in the settings of osteoarthritis and focal cartilage defects. However, little consensus exists regarding the indications for cellular therapies, optimal cell sources, methods of preparation and delivery, or means by which outcomes should be reported. We present a systematic review of the current literature regarding the safety and efficacy of cellular therapy delivered by intra-articular injection in the knee that provided a Level of Evidence of III or higher. A total of 420 papers were screened. Methodological quality was assessed using a modified Coleman methodology score. Only 6 studies (4 Level II and 2 Level III) met the criteria to be included in this review; 3 studies were on treatment of osteoarthritis and 3 were on treatment of focal cartilage defects. These included 4 randomized controlled studies without blinding, 1 prospective cohort study, and 1 retrospective therapeutic case-control study. The studies varied widely with respect to cell sources, cell characterization, adjuvant therapies, and assessment of outcomes. Outcome was reported in a total of 300 knees (124 in the osteoarthritis studies and 176 in the cartilage defect studies). Mean follow-up was 21.0 months (range, 12 to 36 months). All studies reported improved outcomes with intra-articular cellular therapy and no major adverse events. The mean modified Coleman methodology score was 59.1 ± 16 (range, 32 to 82). The studies of intra-articular cellular therapy injections for osteoarthritis and focal cartilage defects in the human knee suggested positive results with respect to clinical improvement and safety. However, the improvement was modest and a placebo effect cannot be disregarded. The overall quality of the literature was poor, and the methodological quality was fair, even among Level-II and III studies. Effective clinical assessment and optimization of injection therapies will demand greater attention to study methodology, including blinding; standardized quantitative methods for cell harvesting, processing, characterization, and delivery; and standardized reporting of clinical and structural outcomes. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence. Copyright © 2016 by The Journal of Bone and Joint Surgery, Incorporated.

CORRELATION OF ARTICULAR CARTILAGE THICKNESS MEASUREMENTS MADE WITH MAGNETIC RESONANCE IMAGING, MAGNETIC RESONANCE ARTHROGRAPHY, AND COMPUTED TOMOGRAPHIC ARTHROGRAPHY WITH GROSS ARTICULAR CARTILAGE THICKNESS IN THE EQUINE METACARPOPHALANGEAL JOINT.

PubMed

Porter, Erin G; Winter, Matthew D; Sheppard, Barbara J; Berry, Clifford R; Hernandez, Jorge A

2016-09-01

Osteoarthritis of the metacarpophalangeal joint is common cause of lameness in equine athletes, and is hallmarked by articular cartilage damage. An accurate, noninvasive method for measuring cartilage thickness would be beneficial to screen for cartilage injury and allow for prompt initiation of interventional therapy. The objective of this methods comparison study was to compare computed tomographic arthrography (CTA), magnetic resonance imaging (MRI), and magnetic resonance arthrography (MRA) measurements of articular cartilage thickness with gross measurements in the metacarpophalangeal joint of Thoroughbred horses. Fourteen cadaveric, equine thoracic limbs were included. Limbs were excluded from the study if pathology of the metacarpophalangeal articular cartilage was observed with any imaging modality. Articular cartilage thickness was measured in nine regions of the third metacarpal bone and proximal phalanx on sagittal plane MRI sequences. After intra-articular contrast administration, the measurements were repeated on sagittal plane MRA and sagittal CTA reformations. In an effort to increase cartilage conspicuity, the volume of intra-articular contrast was increased from 14.5 ml, to maximal distention for the second set of seven limbs. Mean and standard deviation values were calculated, and linear regression analysis was used to determine correlations between gross and imaging measurements of cartilage thickness. This study failed to identify one imaging test that consistently yielded measurements correlating with gross cartilage thickness. Even with the use of intra-articular contrast, cartilage surfaces were difficult to differentiate in regions where the cartilage surfaces of the proximal phalanx and third metacarpal bone were in close contact with each other. © 2016 American College of Veterinary Radiology.

Chondrogenic properties of collagen type XI, a component of cartilage extracellular matrix.

PubMed

Li, Ang; Wei, Yiyong; Hung, Clark; Vunjak-Novakovic, Gordana

2018-08-01

Cartilage extracellular matrix (ECM) has been used for promoting tissue engineering. However, the exact effects of ECM on chondrogenesis and the acting mechanisms are not well understood. In this study, we investigated the chondrogenic effects of cartilage ECM on human mesenchymal stem cells (MSCs) and identified the contributing molecular components. To this end, a preparation of articular cartilage ECM was supplemented to pellets of chondrogenically differentiating MSCs, pellets of human chondrocytes, and bovine articular cartilage explants to evaluate the effects on cell proliferation and the production of cartilaginous matrix. Selective enzymatic digestion and screening of ECM components were conducted to identify matrix molecules with chondrogenic properties. Cartilage ECM promoted MSC proliferation, production of cartilaginous matrix, and maturity of chondrogenic differentiation, and inhibited the hypertrophic differentiation of MSC-derived chondrocytes. Selective digestion of ECM components revealed a contributory role of collagens in promoting chondrogenesis. The screening of various collagen subtypes revealed strong chondrogenic effect of collagen type XI. Finally, collagen XI was found to promote production and inhibit degradation of cartilage matrix in human articular chondrocyte pellets and bovine articular cartilage explants. Our results indicate that cartilage ECM promotes chondrogenesis and inhibits hypertrophic differentiation in MSCs. Collagen type XI is the ECM component that has the strongest effects on enhancing the production and inhibiting the degradation of cartilage matrix. Copyright © 2018 Elsevier Ltd. All rights reserved.

Robotic Powered Transfer Mechanism modeling on Human Muscle Structure

NASA Astrophysics Data System (ADS)

Saito, Yukio

It is considered in engineering that one power source can operate one joint. However, support movement mechanism of living organism is multi joint movement mechanism. Considerably different from mechanical movement mechanism, two pairs of uni-articular muscles and a pair of bi-articular muscles are involved in it. In leg, movements observed in short run including leg idling, heel contact and toeing are operated by bi-articular muscles of the thigh showing strong legs to support body weight. Pursuit of versatility in welfare robot brings its comparison with conventional machinery or industrial robot to the fore. Request for safety and technology allowing elderly people to operate the robot is getting stronger in the society. The robot must be safe when it is used together with other welfare equipment and simpler system avoiding difficult operation has to be constructed. Appearance of recent care and assistance robot is getting similar to human arm in comparison with industrial robot. Being easily able to imagine from industrial robot, mid-heavyweight articulated robot to support 60-70kgf combined with large output motor and reduction gears is next to impossible to be installed in the bath room. This research indicated that upper limb arm and lower limb thigh of human and animals are holding coalitional muscles and movement of uni-artcular muscle and bi-articular muscle conjure the image of new actuators.

Effects of Multiple Intra-articular Injections of 0.5% Bupivacaine on Normal and Osteoarthritic Joints in Rats.

PubMed

Iwasaki, Koji; Sudo, Hideki; Kasahara, Yasuhiko; Yamada, Katsuhisa; Ohnishi, Takashi; Tsujimoto, Takeru; Iwasaki, Norimasa

2016-10-01

To determine the in vivo effects of multiple local anesthetic injections of 0.5% bupivacaine on normal and osteoarthritic articular cartilage. Rats with normal knee joints received an intra-articular injection of 0.9% saline solution or 0.5% bupivacaine in their right knees joint once a week for 5 consecutive weeks, starting 4 weeks after the beginning of the experiment. Rats were humanely killed at 8, 16, and 24 weeks. In a parallel experiment, rats underwent anterior cruciate ligament transection to induce osteoarthritic changes. These rats were subjected to the same protocol as those with normal knee joints, starting 4 weeks after the procedure. Static weight-bearing tests were performed on both hind limbs to evaluate changes in weight-bearing ability throughout the experiments. Rats were humanely killed at 8 and 16 weeks. Cell viability was assessed with confocal microscopy, using samples from the distal femur. Histologic assessment of osteoarthritis was performed using samples from the tibial plateau based on the Osteoarthritis Research Society International (OARSI) cartilage histopathology assessment system (i.e., OARSI score). Static weight-bearing tests showed no significant changes after intra-articular injection of saline solution or bupivacaine, and bupivacaine injection did not increase weight bearing compared with saline solution injection, regardless of whether there were osteoarthritic changes. There were also no significant differences in cell viability, cell density, or OARSI scores between the saline solution and bupivacaine groups at each time point, regardless of whether osteoarthritic changes were induced. This study suggested that single or intermittent intra-articular bupivacaine injections might not have deleterious effects on either osteoarthritic or normal joints. There is no strong evidence that intra-articular bupivacaine injection induces degenerative changes in articular cartilage. Therefore, these results may apply to normal and osteoarthritic joints. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Non-Contact Evaluation for Articular Cartilage Using Ultrasound

NASA Astrophysics Data System (ADS)

Mori, Koji; Nakagawa, Yasuaki; Kuroki, Hiroshi; Nakashima, Keisuke; Ikeuchi, Ken; Mine, Takatomo; Nakamura, Takashi; Kawai, Shinya; Saito, Takashi

In orthopedic field, various new treatments of articular cartilage defect, for example autogenous osteochondral grafts, have been developed. With the spread of these treatments, orthopedists began to focus on the mechanical properties of recovered articular cartilage. The quantitative evaluation of articular cartilage before and after these treatments gives orthopedists the important information to improve these treatments and develop new treatments. We have been investigating the non-contact ultrasonic evaluation for articular cartilage under arthroscopy. In this paper, it was hypothesized that the ultrasonic evaluation depended on the collagen fiber in cartilage. The enzymatically degradation of collagen fiber in cartilage surface was performed. The effect of the degradation on sound velocity, attenuation coefficient and signal intensity, which is the index of cartilage stiffness calculated from the proposed method, was measured. The numerical analysis was performed to clear the relation between the cartilage character and ultrasonic parameters. Experimental and numerical results suggest that the present method can be expanded the sensitive evaluation for cartilage disease in clinical field.

Preclinical and clinical data for the use of mesenchymal stem cells in articular cartilage tissue engineering.

PubMed

Tang, Quen Oak; Carasco, Clare Francesca; Gamie, Zakareya; Korres, Nectarios; Mantalaris, Athanasios; Tsiridis, Eleftherios

2012-10-01

With an ageing population, the prevalence of osteoarthritis (OA) has increased. Mesenchymal Stem Cells (MSCs) have been proposed to be an attractive alternative candidate in the tissue engineering of articular cartilage primarily due to its abundant source, reduced cartilage donor site morbidity, and strong capacity for proliferation and potential to differentiate toward a chondrogenic phenotype. A current overview of human, in vivo, and in vitro evidence on the use of MSCs in cartilage tissue engineering. We demonstrate robust evidence that MSCs have the potential to regenerate articular cartilage. We also identify the complexity of designing a suitable preclinical model and the challenges in considering its clinical application such as type of MSC, scaffold, culture construct and the method by which growth factors are delivered. Of great interest is further characterization of the factors that may prevent MSC-derived chondrocytes to undergo premature hypertrophy and to understand what enables the terminal developmental pathway for permanent hyaline cartilage regeneration. Despite this, there is an abundance of evidence suggesting that MSCs are a desirable cell source and will have significant impact in tissue engineering of cartilage in the future.

The bovine patella as a model of early osteoarthritis.

PubMed

Hargrave-Thomas, E J; Thambyah, A; McGlashan, S R; Broom, N D

2013-12-01

The bovine patella model has been used extensively for studying important structure-function aspects of articular cartilage, including its degeneration. However, the degeneration seen in this model has, to our knowledge, never been adequately compared with human osteoarthritis (OA). In this study, bovine patellae displaying normal to severely degenerate states were compared with human tissue displaying intact cartilage to severe OA. Comparisons of normal and OA features were made with histological scoring, morphometric measurements, and qualitative observations. Differential interference contrast microscopy was used to image early OA changes in the articular cartilage matrix and to investigate whether this method provided comparable quality of visualisation of key structural features with standard histology. The intact bovine cartilage was found to be similar to healthy human cartilage and the degenerate bovine cartilage resembled the human OA tissues with regard to structural disruption, cellularity changes, and staining loss. The extent of degeneration in the bovine tissues matched the mild to moderate range of human OA tissues; however, no bovine samples exhibited late-stage OA. Additionally, in both bovine and human tissues, cartilage degeneration was accompanied by calcified cartilage thickening, tidemark duplication, and the advancement of the cement line by protrusions of bony spicules into the calcified cartilage. This comparison of degeneration in the bovine and human tissues suggests a common pathway for the progression of OA and thus the bovine patella is proposed to be an appropriate model for investigating the structural changes associated with early OA. © 2013 Anatomical Society.

The bovine patella as a model of early osteoarthritis

PubMed Central

Hargrave-Thomas, E J; Thambyah, A; McGlashan, S R; Broom, N D

2013-01-01

The bovine patella model has been used extensively for studying important structure–function aspects of articular cartilage, including its degeneration. However, the degeneration seen in this model has, to our knowledge, never been adequately compared with human osteoarthritis (OA). In this study, bovine patellae displaying normal to severely degenerate states were compared with human tissue displaying intact cartilage to severe OA. Comparisons of normal and OA features were made with histological scoring, morphometric measurements, and qualitative observations. Differential interference contrast microscopy was used to image early OA changes in the articular cartilage matrix and to investigate whether this method provided comparable quality of visualisation of key structural features with standard histology. The intact bovine cartilage was found to be similar to healthy human cartilage and the degenerate bovine cartilage resembled the human OA tissues with regard to structural disruption, cellularity changes, and staining loss. The extent of degeneration in the bovine tissues matched the mild to moderate range of human OA tissues; however, no bovine samples exhibited late-stage OA. Additionally, in both bovine and human tissues, cartilage degeneration was accompanied by calcified cartilage thickening, tidemark duplication, and the advancement of the cement line by protrusions of bony spicules into the calcified cartilage. This comparison of degeneration in the bovine and human tissues suggests a common pathway for the progression of OA and thus the bovine patella is proposed to be an appropriate model for investigating the structural changes associated with early OA. PMID:24111904

Determination of differential gene expression profiles in superficial and deeper zones of mature rat articular cartilage using RNA sequencing of laser microdissected tissue specimens.

PubMed

Mori, Yoshifumi; Chung, Ung-Il; Tanaka, Sakae; Saito, Taku

2014-01-01

Superficial zone (SFZ) cells, which are morphologically and functionally distinct from chondrocytes in deeper zones, play important roles in the maintenance of articular cartilage. Here, we established an easy and reliable method for performance of laser microdissection (LMD) on cryosections of mature rat articular cartilage using an adhesive membrane. We further examined gene expression profiles in the SFZ and the deeper zones of articular cartilage by performing RNA sequencing (RNA-seq). We validated sample collection methods, RNA amplification and the RNA-seq data using real-time RT-PCR. The combined data provide comprehensive information regarding genes specifically expressed in the SFZ or deeper zones, as well as a useful protocol for expression analysis of microsamples of hard tissues.

Distribution of Basement Membrane Molecules, Laminin and Collagen Type IV, in Normal and Degenerated Cartilage Tissues.

PubMed

Foldager, Casper Bindzus; Toh, Wei Seong; Gomoll, Andreas H; Olsen, Bjørn Reino; Spector, Myron

2014-04-01

The objective of the present study was to investigate the presence and distribution of 2 basement membrane (BM) molecules, laminin and collagen type IV, in healthy and degenerative cartilage tissues. Normal and degenerated tissues were obtained from goats and humans, including articular knee cartilage, the intervertebral disc, and meniscus. Normal tissue was also obtained from patella-tibial enthesis in goats. Immunohistochemical analysis was performed using anti-laminin and anti-collagen type IV antibodies. Human and goat skin were used as positive controls. The percentage of cells displaying the pericellular presence of the protein was graded semiquantitatively. When present, laminin and collagen type IV were exclusively found in the pericellular matrix, and in a discrete layer on the articulating surface of normal articular cartilage. In normal articular (hyaline) cartilage in the human and goat, the proteins were found co-localized pericellularly. In contrast, in human osteoarthritic articular cartilage, collagen type IV but not laminin was found in the pericellular region. Nonpathological fibrocartilaginous tissues from the goat, including the menisci and the enthesis, were also positive for both laminin and collagen type IV pericellularly. In degenerated fibrocartilage, including intervertebral disc, as in degenerated hyaline cartilage only collagen type IV was found pericellularly around chondrocytes but with less intense staining than in non-degenerated tissue. In calcified cartilage, some cells were positive for laminin but not type IV collagen. We report differences in expression of the BM molecules, laminin and collagen type IV, in normal and degenerative cartilaginous tissues from adult humans and goats. In degenerative tissues laminin is depleted from the pericellular matrix before collagen type IV. The findings may inform future studies of the processes underlying cartilage degeneration and the functional roles of these 2 extracellular matrix proteins, normally associated with BM.

Radiocarbon dating reveals minimal collagen turnover in both healthy and osteoarthritic human cartilage.

PubMed

Heinemeier, Katja M; Schjerling, Peter; Heinemeier, Jan; Møller, Mathias B; Krogsgaard, Michael R; Grum-Schwensen, Tomas; Petersen, Michael M; Kjaer, Michael

2016-07-06

The poor regenerative capacity of articular cartilage presents a major clinical challenge and may relate to a limited turnover of the cartilage collagen matrix. However, the collagen turnover rate during life is not clear, and it is debated whether osteoarthritis (OA) can influence it. Using the carbon-14 ((14)C) bomb-pulse method, life-long replacement rates of collagen were measured in tibial plateau cartilage from 23 persons born between 1935 and1997 (15 and 8 persons with OA and healthy cartilage, respectively). The (14)C levels observed in cartilage collagen showed that, virtually, no replacement of the collagen matrix happened after skeletal maturity and that neither OA nor tissue damage, per se, influenced collagen turnover. Regional differences in (14)C content across the joint surface showed that cartilage collagen located centrally on the joint surface is formed several years earlier than collagen located peripherally. The collagen matrix of human articular cartilage is an essentially permanent structure that has no significant turnover in adults, even with the occurrence of disease. Copyright © 2016, American Association for the Advancement of Science.

Extra-articular deformities in arthritic knees-a grueling challenge for arthroplasty surgeons: An evidence-based update

PubMed Central

Khanna, Vishesh; Sambandam, Senthil N.; Ashraf, Munis; Mounasamy, Varatharaj

2018-01-01

Critical to the success of a total knee arthroplasty (TKA) is the anatomical alignment. This may appear as a challenge in an extra-articular deformity (EAD) that may be inherent in certain people or result from fracture malunion, congenital disorders, nutritional, metabolic and infective causes. This appraisal aimed at providing the reader with an up-todate overview of the research carried out on, and existent evidence of EAD correction while planning a TKA. We reviewed the current English literature on TKA in extra-articular knee deformities. Among the published data, a common initial approach of mandatory clinical and radiological assessment emerges as an obligatory step while handling cases with EAD. While several methods of managing the deformity and arthritis have been described, a broad division into intra-articular and extra-articular means can be deciphered. The relatively old-school, yet reliable thought process of extra-articular correction allows an all-inclusive restoration of alignment with the inherent complications related to the necessary osteotomy. A cohort of younger and more venturesome surgeons seem inclined towards performing navigated, intra-articular correction for mild to moderate and sometimes, severe deformities. The crux of the matter lies is obtaining a well-balanced knee without violating the all-important cruciates. Restoring the patient’s ambulatory status seems sooner with the intra-articular methods which are also more precise in determining the axes and while removing minimum bone. Greatest satisfaction is accomplished in those with less grotesque, rotationallyaligned knees while meticulously balancing soft-tissues and encouraging earlier weightbearing. PMID:29564077

Optimization of Extracellular Matrix Synthesis and Accumulation by Human Articular Chondrocytes in 3-Dimensional Construct with Repetitive Hydrostatic Pressure.

PubMed

Ogura, Takahiro; Tsuchiya, Akihiro; Minas, Tom; Mizuno, Shuichi

2018-04-01

Objective The effects of hydrostatic pressure (HP) on the matrix synthesis by human articular chondrocytes have been reported elsewhere. In order to optimize the production of extracellular matrix, we aimed to clarify the effects of repetitive HP on metabolic function by human articular chondrocytes. Design The human articular chondrocytes were expanded and embedded within a collagen gel/sponge scaffold. We incubated these constructs with and without HP followed by atmospheric pressure (AP) and repeated the second HP followed by AP over 14 days. Genomic, biochemical, and histological evaluation were performed to compare the effects of each regimen on the constructs. Results The gene expressions of collagen type II and aggrecan core protein were significantly upregulated with repetitive HP regimens compared with a single HP or AP by 14 days ( P < 0.01 or 0.05). Matrix metalloptoteinase-13 (MMP-13) in AP was upregulated significantly compared to other HP regimens at day 14 ( P < 0.01). No significant difference was observed in tissue inhibitor of metalloproteinases-II. Immunohistology demonstrated that application of HP (both repetitive and single) promoted the accumulation of specific extracellular matrix and reduced a MMP-13. A single regimen of HP followed by AP significantly increased the amount of sulfated glycosaminoglycan than that of the AP, whereas repetitive HP remained similar level of that of the AP. Conclusions Repetitive HP had a greater effect on anabolic activity by chondrocytes than a single HP regimen, which will be advantageous for producing a matrix-rich cell construct.

Wnt signaling is involved in human articular chondrocyte de-differentiation in vitro.

PubMed

Sassi, N; Laadhar, L; Allouche, M; Zandieh-Doulabi, B; Hamdoun, M; Klein-Nulend, J; Makni, S; Sellami, S

2014-01-01

Osteoarthritis is the most prevalent form of arthritis in the world. Certain signaling pathways, such as the wnt pathway, are involved in cartilage pathology. Osteoarthritic chondrocytes undergo morphological and biochemical changes that lead to chondrocyte de-differentiation. We investigated whether the Wnt pathway is involved in de-differentiation of human articular chondrocytes in vitro. Human articular chondrocytes were cultured for four passages in the presence or absence of IL-1 in monolayer or micromass culture. Changes in cell morphology were monitored by light microscopy. Protein and gene expression of chondrocyte markers and Wnt pathway components were determined by Western blotting and qPCR after culture. After culturing for four passages, chondrocytes exhibited a fibroblast-like morphology. Collagen type II and aggrecan protein and gene expression decreased, while collagen type I, matrix metalloproteinase 13, and nitric oxide synthase expressions increased. Wnt molecule expression profiles changed; Wnt5a protein expression, the Wnt target gene, c-jun, and in Wnt pathway regulator, sFRP4 increased. Treatment with IL-1 caused chondrocyte morphology to become more filament-like. This change in morphology was accompanied by extinction of col II expression and increased col I, MMP13 and eNOS expression. Changes in expression of the Wnt pathway components also were observed. Wnt7a decreased significantly, while Wnt5a, LRP5, β-catenin and c-jun expressions increased. Culture of human articular chondrocytes with or without IL-1 not only induced chondrocyte de-differentiation, but also changed the expression profiles of Wnt components, which suggests that the Wnt pathway is involved in chondrocyte de-differentiation in vitro.

Opioids as an alternative to amide-type local anaesthetics for intra-articular application.

PubMed

Ickert, Irina; Herten, Monika; Vogl, Melanie; Ziskoven, Christoph; Zilkens, Christoph; Krauspe, Rüdiger; Kircher, Jörn

2015-09-01

Recently, the safety profile of local anaesthetics in intra-articular use became into focus of investigation. Opioid drugs have a different mode of action and may be a safe and potent alternative for intra-articular application. The purpose of this in vitro study is to provide evidence for significant chondrotoxicity of amide-type local anaesthetics even after short-term application on human chondrocytes and to demonstrate the absence of such negative effects for opioids [morphine, morphine-6-glucuronide (M6G)]. Visually intact cartilage explants of human, mainly osteoarthritic joints (n = 9), were harvested and cultivated in monolayer for expansion and transferred into alginate bead. The beads were incubated for increasing incubation times (15 min, 1 and 4 h) in decreasing concentrations (full, ½, ¼ for 15 min) of bupivacaine, ropivacaine, morphine, M6G or saline control. Adenosine triphosphate content of 798 beads was measured 3 days post-incubation to assess cell viability. A clear ranking of cytotoxic potency: bupivacaine > ropivacaine > morphine = M6G = saline was observed. Results reveal a dose- and time-dependent manner of cytotoxic effects on human chondrocytes for bupivacaine and ropivacaine but not for opioids. Cell viability after exposure to morphine and M6G was comparable to exposure to saline. The results confirm dose- and time-dependent cytotoxic effects on human chondrocytes for amide-type local anaesthetics. This study confirms the safety of morphine and M6G in terms of an absence of cytotoxic effects after intra-articular application, making them safe potential alternatives in clinical practice.

Morphometric anatomical and CT study of the human adult sacroiliac region.

PubMed

Postacchini, Roberto; Trasimeni, Guido; Ripani, Francesca; Sessa, Pasquale; Perotti, Stefano; Postacchini, Franco

2017-01-01

To identify and describe the morphometry and CT features of the articular and extra-articular portions of the sacroiliac region. The resulting knowledge might help to avoid complications in sacroiliac joint (SIJ) fusion. We analyzed 102 dry hemi-sacra, 80 ilia, and 10 intact pelves and assessed the pelvic computerized tomography (CT) scans of 90 patients, who underwent the examination for conditions not involving the pelvis. We assessed both the posterior aspect of sacrum with regard to the depressions located externally to the lateral sacral crest at the level of the proximal three sacral vertebrae and the posteroinferior aspect of ilium. Coronal and axial CT scans of the SIJ of patients were obtained and the joint space was measured. On each side, the sacrum exhibits three bone depressions, not described in anatomic textbooks or studies, facing the medial aspect of the posteroinferior ilium, not yet described in detail. Both structures are extra-articular portions situated posteriorly to the SIJ. Coronal CT scans of patients showing the first three sacral foramens and the interval between sacrum and ilium as a continuous space display only the S1 and S3 portions of SIJ, the intermediate portion being extra-articular. The S2 portion is visible on the most anterior coronal scan. Axial scans show articular and extra-articular portions and features improperly described as anatomic variations. Extra-articular portions of the sacroiliac region, not yet described exhaustively, have often been confused with SIJ. Coronal CT scans through the middle part of sacrum, the most used to evaluate degenerative and inflammatory conditions of SIJ, show articular and extra-articular portions of the region.

Anatomical study of the articular branches innervated the hip and knee joint with reference to mechanism of referral pain in hip joint disease patients.

PubMed

Sakamoto, Junya; Manabe, Yoshitaka; Oyamada, Joichi; Kataoka, Hideki; Nakano, Jiro; Saiki, Kazunobu; Okamoto, Keishi; Tsurumoto, Toshiyuki; Okita, Minoru

2018-07-01

Referred pain in the anterior knee joint is the most common symptom in hip disease patients. The development of referred pain is considered to be related to dichotomizing peripheral sensory fibers. However, no gross anatomical findings identify any dichotomizing fibers innervating both the hip and knee joints. We dissected the femoral and obturator nerves in human cadavers to investigate the distribution of the articular branches in the hip and knee joints. Fourteen embalmed left lower limbs from 14 Japanese adult cadavers (five from females, nine from males, average age 73.8 ± 14.1 years) were observed macroscopically. The articular branches of the femoral and obturator nerves were dissected at the anterior margin of the groin toward the thigh region. After dissections of the articular nerves of the hip joints, the femoral and obturator nerves were exposed from proximally to distally to identify the articular nerves of the knee joints. The branching pattern of the articular branches in the hip and knee joints was recorded. In six of 14 limbs (42.9%), the femoral nerve supplied articular branches to the anteromedial aspect of both the hip and knee joints. These articular branches were derived from the same bundle of femoral nerve. These gross anatomical findings suggested that dichotomizing peripheral sensory fibers innervate the hip and knee joints and these could relate to the referred pain confirmed in the anterior knee joints of patients with hip disease. Clin. Anat. 31:705-709, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

AMPA/kainate glutamate receptors contribute to inflammation, degeneration and pain related behaviour in inflammatory stages of arthritis

PubMed Central

Bonnet, Cleo S; Williams, Anwen S; Gilbert, Sophie J; Harvey, Ann K; Evans, Bronwen A; Mason, Deborah J

2015-01-01

Objectives Synovial fluid glutamate concentrations increase in arthritis. Activation of kainate (KA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors (GluRs) increase interleukin-6 (IL-6) release and cause arthritic pain, respectively. We hypothesised that AMPA and KA GluRs are expressed in human arthritis, and that intra-articular NBQX (AMPA/KA GluR antagonist) prevents pain and pathology in antigen-induced arthritis (AIA). Methods GluR immunohistochemistry was related to synovial inflammation and degradation in osteoarthritis (OA) and rheumatoid arthritis (RA). A single intra-articular NBQX injection was given at induction, and knee swelling and gait of AIA and AIA+NBQX rats compared over 21 days, before imaging, RT-qPCR, histology and immunohistochemistry of joints. Effects of NBQX on human primary osteoblast (HOB) activity were determined. Results AMPAR2 and KA1 immunolocalised to remodelling bone, cartilage and synovial cells in human OA and RA, and rat AIA. All arthritic tissues showed degradation and synovial inflammation. NBQX reduced GluR abundance, knee swelling (p<0.001, days 1–21), gait abnormalities (days 1–2), end-stage joint destruction (p<0.001), synovial inflammation (p<0.001), and messenger RNA expression of meniscal IL-6 (p<0.05) and whole joint cathepsin K (p<0.01). X-ray and MRI revealed fewer cartilage and bone erosions, and less inflammation after NBQX treatment. NBQX reduced HOB number and prevented mineralisation. Conclusions AMPA/KA GluRs are expressed in human OA and RA, and in AIA, where a single intra-articular injection of NBQX reduced swelling by 33%, and inflammation and degeneration scores by 34% and 27%, respectively, exceeding the efficacy of approved drugs in the same model. AMPA/KA GluR antagonists represent a potential treatment for arthritis. PMID:24130267

Intra-articular therapies for osteoarthritis.

PubMed

Yu, Shirley P; Hunter, David J

2016-10-01

Conventional medical therapies for osteoarthritis are mainly palliative in nature, aiming to control pain and symptoms. Traditional intra-articular therapies are not recommended in guidelines as first line therapy, but are potential alternatives, when conventional therapies have failed. Current and future intra-articular drug therapies for osteoarthritis are highlighted, including corticosteroids, hyaluronate, and more controversial treatments marketed commercially, namely platelet rich plasma and mesenchymal cell therapy. Intraarticular disease modifying osteoarthritis drugs are the future of osteoarthritis treatments, aiming at structural modification and altering the disease progression. Interleukin-1β inhibitor, bone morphogenic protein-7, fibroblast growth factor 18, bradykinin B2 receptor antagonist, human serum albumin, and gene therapy are discussed in this review. The evolution of drug development in osteoarthritis is limited by the ability to demonstrate effect. High quality trials are required to justify the use of existing intra-articular therapies and to advocate for newer, promising therapies. Challenges in osteoarthritis therapy research are fundamentally related to the complexity of the pathological mechanisms of osteoarthritis. Novel drugs offer hope in a disease with limited medical therapy options. Whether these future intra-articular therapies will provide clinically meaningful benefits, remains unknown.

Application of an acoustofluidic perfusion bioreactor for cartilage tissue engineering.

PubMed

Li, Siwei; Glynne-Jones, Peter; Andriotis, Orestis G; Ching, Kuan Y; Jonnalagadda, Umesh S; Oreffo, Richard O C; Hill, Martyn; Tare, Rahul S

2014-12-07

Cartilage grafts generated using conventional static tissue engineering strategies are characterised by low cell viability, suboptimal hyaline cartilage formation and, critically, inferior mechanical competency, which limit their application for resurfacing articular cartilage defects. To address the limitations of conventional static cartilage bioengineering strategies and generate robust, scaffold-free neocartilage grafts of human articular chondrocytes, the present study utilised custom-built microfluidic perfusion bioreactors with integrated ultrasound standing wave traps. The system employed sweeping acoustic drive frequencies over the range of 890 to 910 kHz and continuous perfusion of the chondrogenic culture medium at a low-shear flow rate to promote the generation of three-dimensional agglomerates of human articular chondrocytes, and enhance cartilage formation by cells of the agglomerates via improved mechanical stimulation and mass transfer rates. Histological examination and assessment of micromechanical properties using indentation-type atomic force microscopy confirmed that the neocartilage grafts were analogous to native hyaline cartilage. Furthermore, in the ex vivo organ culture partial thickness cartilage defect model, implantation of the neocartilage grafts into defects for 16 weeks resulted in the formation of hyaline cartilage-like repair tissue that adhered to the host cartilage and contributed to significant improvements to the tissue architecture within the defects, compared to the empty defects. The study has demonstrated the first successful application of the acoustofluidic perfusion bioreactors to bioengineer scaffold-free neocartilage grafts of human articular chondrocytes that have the potential for subsequent use in second generation autologous chondrocyte implantation procedures for the repair of partial thickness cartilage defects.

Contour interpolated radial basis functions with spline boundary correction for fast 3D reconstruction of the human articular cartilage from MR images

DOE Office of Scientific and Technical Information (OSTI.GOV)

Javaid, Zarrar; Unsworth, Charles P., E-mail: c.unsworth@auckland.ac.nz; Boocock, Mark G.

2016-03-15

Purpose: The aim of this work is to demonstrate a new image processing technique that can provide a “near real-time” 3D reconstruction of the articular cartilage of the human knee from MR images which is user friendly. This would serve as a point-of-care 3D visualization tool which would benefit a consultant radiologist in the visualization of the human articular cartilage. Methods: The authors introduce a novel fusion of an adaptation of the contour method known as “contour interpolation (CI)” with radial basis functions (RBFs) which they describe as “CI-RBFs.” The authors also present a spline boundary correction which further enhancesmore » volume estimation of the method. A subject cohort consisting of 17 right nonpathological knees (ten female and seven male) is assessed to validate the quality of the proposed method. The authors demonstrate how the CI-RBF method dramatically reduces the number of data points required for fitting an implicit surface to the entire cartilage, thus, significantly improving the speed of reconstruction over the comparable RBF reconstruction method of Carr. The authors compare the CI-RBF method volume estimation to a typical commercial package (3D DOCTOR), Carr’s RBF method, and a benchmark manual method for the reconstruction of the femoral, tibial, and patellar cartilages. Results: The authors demonstrate how the CI-RBF method significantly reduces the number of data points (p-value < 0.0001) required for fitting an implicit surface to the cartilage, by 48%, 31%, and 44% for the patellar, tibial, and femoral cartilages, respectively. Thus, significantly improving the speed of reconstruction (p-value < 0.0001) by 39%, 40%, and 44% for the patellar, tibial, and femoral cartilages over the comparable RBF model of Carr providing a near real-time reconstruction of 6.49, 8.88, and 9.43 min for the patellar, tibial, and femoral cartilages, respectively. In addition, it is demonstrated how the CI-RBF method matches the volume estimation of a typical commercial package (3D DOCTOR), Carr’s RBF method, and a benchmark manual method for the reconstruction of the femoral, tibial, and patellar cartilages. Furthermore, the performance of the segmentation method used for the extraction of the femoral, tibial, and patellar cartilages is assessed with a Dice similarity coefficient, sensitivity, and specificity measure providing high agreement to manual segmentation. Conclusions: The CI-RBF method provides a fast, accurate, and robust 3D model reconstruction that matches Carr’s RBF method, 3D DOCTOR, and a manual benchmark method in accuracy and significantly improves upon Carr’s RBF method in data requirement and computational speed. In addition, the visualization tool has been designed to quickly segment MR images requiring only four mouse clicks per MR image slice.« less

On Detailed Contrast of Biomedical Object in X-ray Dark-Field Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shimao, Daisuke; Mori, Koichi; Sugiyama, Hiroshi

2007-01-19

Over the past 10 years, refraction-based X-ray imaging has been studied together with a perspective view to clinical application. X-ray Dark-Field Imaging that utilizes a Laue geometry analyzer has recently been proposed and has the proven ability to depict articular cartilage in an intact human finger. In the current study, we researched detailed image contrast using X-ray Dark-Field Imaging by observing the edge contrast of an acrylic rod as a simple case, and found differences in image contrast between the right and left edges of the rod. This effect could cause undesirable contrast in the thin articular cartilage on themore » head of the phalanx. To avoid overlapping with this contrast at the articular cartilage, which would lead to a wrong diagnosis, we suggest that a joint surface on which articular cartilage is located should be aligned in the same sense as the scattering vector of the Laue case analyzer crystal. Defects of articular cartilage were successfully detected under this condition. When utilized under appropriate imaging conditions, X-ray Dark-Field Imaging will be a powerful tool for the diagnosis of arthropathy, as minute changes in articular cartilage may be early-stage features of this disease.« less

Infrared microspectroscopic determination of collagen cross-links in articular cartilage

NASA Astrophysics Data System (ADS)

Rieppo, Lassi; Kokkonen, Harri T.; Kulmala, Katariina A. M.; Kovanen, Vuokko; Lammi, Mikko J.; Töyräs, Juha; Saarakkala, Simo

2017-03-01

Collagen forms an organized network in articular cartilage to give tensile stiffness to the tissue. Due to its long half-life, collagen is susceptible to cross-links caused by advanced glycation end-products. The current standard method for determination of cross-link concentrations in tissues is the destructive high-performance liquid chromatography (HPLC). The aim of this study was to analyze the cross-link concentrations nondestructively from standard unstained histological articular cartilage sections by using Fourier transform infrared (FTIR) microspectroscopy. Half of the bovine articular cartilage samples (n=27) were treated with threose to increase the collagen cross-linking while the other half (n=27) served as a control group. Partial least squares (PLS) regression with variable selection algorithms was used to predict the cross-link concentrations from the measured average FTIR spectra of the samples, and HPLC was used as the reference method for cross-link concentrations. The correlation coefficients between the PLS regression models and the biochemical reference values were r=0.84 (p<0.001), r=0.87 (p<0.001) and r=0.92 (p<0.001) for hydroxylysyl pyridinoline (HP), lysyl pyridinoline (LP), and pentosidine (Pent) cross-links, respectively. The study demonstrated that FTIR microspectroscopy is a feasible method for investigating cross-link concentrations in articular cartilage.

A clinico-radiographic analysis of sagittal condylar guidance determined by protrusive interocclusal registration and panoramic radiographic images in humans

PubMed Central

Prasad, Krishna D.; Shah, Namrata; Hegde, Chethan

2012-01-01

Purpose: To evaluate the correlation between sagittal condylar guidance obtained by protrusive interocclusal records and panoramic radiograph tracing methods in human dentulous subjects. Materials and Methods: The sagittal condylar guidance was determined in 75 dentulous subjects by protrusive interocclusal records using Aluwax through a face bow transfer (HANAU™ Spring Bow, Whip Mix Corporation, USA) to a semi-adjustable articulator (HANAU™ Wide-Vue Articulator, Whip Mix Corporation, USA). In the same subjects, the sagittal outline of the articular eminence and glenoid fossa was traced in panoramic radiographs. The sagittal condylar path inclination was constructed by joining the heights of curvature in the glenoid fossa and the corresponding articular eminence. This was then related to the constructed Frankfurt's horizontal plane to determine the radiographic angle of sagittal condylar guidance. Results: A strong positive correlation existed between right and left condylar guidance by the protrusive interocclusal method (P 0.000) and similarly by the radiographic method (P 0.013). The mean difference between the condylar guidance obtained using both methods were 1.97° for the right side and 3.18° for the left side. This difference between the values by the two methods was found to be highly significant for the right (P 0.003) and left side (P 0.000), respectively. The sagittal condylar guidance obtained from both methods showed a significant positive correlation on right (P 0.000) and left side (P 0.015), respectively. Conclusion: Panoramic radiographic tracings of the sagittal condylar path guidance may be made relative to the Frankfurt's horizontal reference plane and the resulting condylar guidance angles used to set the condylar guide settings of semi-adjustable articulators. PMID:23633793

Formation of Hyaline Cartilage Tissue by Passaged Human Osteoarthritic Chondrocytes.

PubMed

Bianchi, Vanessa J; Weber, Joanna F; Waldman, Stephen D; Backstein, David; Kandel, Rita A

2017-02-01

When serially passaged in standard monolayer culture to expand cell number, articular chondrocytes lose their phenotype. This results in the formation of fibrocartilage when they are used clinically, thus limiting their use for cartilage repair therapies. Identifying a way to redifferentiate these cells in vitro is critical if they are to be used successfully. Transforming growth factor beta (TGFβ) family members are known to be crucial for regulating differentiation of fetal limb mesenchymal cells and mesenchymal stromal cells to chondrocytes. As passaged chondrocytes acquire a progenitor-like phenotype, the hypothesis of this study was that TGFβ supplementation will stimulate chondrocyte redifferentiation in vitro in serum-free three-dimensional (3D) culture. Human articular chondrocytes were serially passaged twice (P2) in monolayer culture. P2 cells were then placed in high-density (3D) culture on top of membranes (Millipore) and cultured for up to 6 weeks in chemically defined serum-free redifferentiation media (SFRM) in the presence or absence of TGFβ. The tissues were evaluated histologically, biochemically, by immunohistochemical staining, and biomechanically. Passaged human chondrocytes cultured in SFRM supplemented with 10 ng/mL TGFβ3 consistently formed a continuous layer of articular-like cartilage tissue rich in collagen type 2 and aggrecan and lacking collagen type 1 and X in the absence of a scaffold. The tissue developed a superficial zone characterized by expression of lubricin and clusterin with horizontally aligned collagen fibers. This study suggests that passaged human chondrocytes can be used to bioengineer a continuous layer of articular cartilage-like tissue in vitro scaffold free. Further study is required to evaluate their ability to repair cartilage defects in vivo.

Phlpp1 facilitates post-traumatic osteoarthritis and is induced by inflammation and promoter demethylation in human osteoarthritis

PubMed Central

Bradley, Elizabeth W.; Carpio, Lomeli R.; McGee-Lawrence, Meghan E.; Becerra, Clara Castillejo; Amanatullah, Derek F.; Ta, Lauren E.; Otero, Miguel; Goldring, Mary B.; Kakar, Sanjeev; Westendorf, Jennifer J.

2016-01-01

OBJECTIVE Osteoarthritis (OA) is the most common form of arthritis and a leading cause of disability. OA is characterized by articular chondrocyte deterioration, subchondral bone changes and debilitating pain. One strategy to promote cartilage regeneration and repair is to accelerate proliferation and matrix production of articular chondrocytes. We previously reported that the protein phosphatase Phlpp1 controls chondrocyte differentiation by regulating the activities of anabolic kinases. Here we examined the role of Phlpp1 in osteoarthritis progression in a murine model. We also assessed PHLPP1 expression and promoter methylation. DESIGN Knee joints of WT and Phlpp1−/− mice were surgically destabilized by transection of the medial meniscal ligament (DMM). Mice were assessed for signs of OA progression via radiographic and histological analyses, and pain assessment for mechanical hypersensitivity using the von Frey assay. Methylation of the PHLPP1 promoter and PHLPP1 expression was evaluated in human articular cartilage and chondrocyte cell lines. RESULTS Following DMM surgeries, Phlpp1 deficient mice showed fewer signs of OA and cartilage degeneration. Mechanical allodynia associated with DMM surgeries was also attenuated in Phlpp1−/− mice. PHLPP1 was highly expressed in human articular cartilage from OA patients, but was undetectable in cartilage specimens from femoral neck fractures. Higher PHLPP1 levels correlated with less PHLPP1 promoter CpG methylation in cartilage from OA patients. Blocking cytosine methylation or treatment with inflammatory mediators enhanced PHLPP1 expression in human chondrocyte cell lines. CONCLUSION Phlpp1 deficiency protects against OA progression while CpG demethylation and inflammatory responses promote PHLPP1 expression. PMID:26746148

Fibulin-3 in joint aging and osteoarthritis pathogenesis

PubMed Central

Hasegawa, Akihiko; Yonezawa, Tomo; Taniguchi, Noboru; Otabe, Koji; Akasaki, Yukio; Matsukawa, Tetsuya; Saito, Masahiko; Neo, Masashi; Marmorstein, Lihua Y.; Lotz, Martin K.

2016-01-01

Objectives The EFEMP1 gene encoding fibulin-3 is specifically expressed in the superficial zone of articular cartilage. This study examined fibulin-3 expression patterns in joint aging and osteoarthritis (OA) and the role of fibulin-3 in OA pathogenesis. Methods Immunohistochemical analysis was performed on normal and OA human and mouse knee cartilage. Experimental OA was induced in wild type and fibulin-3−/− mice and OA severity was evaluated by histological scoring. To examine fibulin-3 function, chondrocyte monolayer cultures were transfected with siRNA for quantitative PCR and Western blot analyses. Bone marrow mesenchymal stem cells (MSC) were transduced with EFEMP1 lentivirus and analyzed for chondrogenesis markers. Results Fibulin-3 was specifically expressed in the SZ of normal cartilage in human and mouse knee joints and declined with aging. Both aging-related OA and experimental OA were significantly more severe in fibulin-3−/− mice compared with wild type mice. Fibulin-3 expression was high in undifferentiated MSC and decreased during chondrogenesis. Suppression of fibulin-3 by siRNA significantly increased SOX9, collagen II and aggrecan in articular chondrocytes, while overexpression of fibulin-3 inhibited chondrogenesis in MSC. Conclusion Fibulin-3 is specifically expressed in the SZ of articular cartilage and its expression is reduced in aging and OA. Fibulin-3 regulates differentiation of adult progenitor cells and its aging-related decline is an early event in OA pathogenesis. Preventing or restoring aging-associated loss of fibulin-3 in SZ chondrocytes has potential to delay or prevent onset of OA. PMID:27780308

Towards Regeneration of Articular Cartilage

PubMed Central

Iwamoto, Masahiro; Ohta, Yoichi; Larmour, Colleen; Enomoto-Iwamoto, Motomi

2014-01-01

Articular cartilage is classified into permanent hyaline cartilage and has significant differences in structure, extracelluar matrix components, gene expression profile, and mechanical property from transient hyaline cartilage found in growth plate. In the process of synovial joint development, articular cartilage is originated from the interzone, developing at the edge of the cartilaginous anlagen, it establishes zonal structure over time and supports smooth movement of the synovial joint through life. The cascade actions of key regulators such as Wnts, GDF5, Erg, and PTHLH coordinate sequential steps of articular cartilage formation. Articular chondrocytes are restrictedly controlled not to differentiate into a hypertrophic stage by autocrine and paracrine factors and extracerllular matrix microenvironment, but retain potential to undergo hypertrophy. The basal calcified zone of articular cartilage is connected with subchondral bone, but not invaded by blood vessels nor replaced by bone, which is highly contrasted with the growth plate. Articular cartilage has limited regenerative capacity, but likely possesses and potentially uses intrinsic stem cell source in the superficial layer, Ranvier’s groove, the intra-articular tissues such as synovium and fat pad, and marrow below the subchondral bone. Considering the biological views on articular cartilage, several important points are raised for regeneration of articular cartilage. We should evaluate the nature of regenerated cartilage as permanent hyaline cartilage and not just hyaline cartilage. We should study how a hypertrophic phenotype of transplanted cells can be lastingly suppressed in regenerating tissue. Further, we should develop the methods and reagents to activate recruitment of intrinsic stem/progenitor cells into the damaged site. PMID:24078496

Characterization of the surface and interfacial properties of the lamina splendens

NASA Astrophysics Data System (ADS)

Rexwinkle, Joe T.; Hunt, Heather K.; Pfeiffer, Ferris M.

2017-06-01

Joint disease affects approximately 52.5 million patients in the United States alone, costing 80.8 billion USD in direct healthcare costs. The development of treatment programs for joint disease and trauma requires accurate assessment of articular cartilage degradation. The articular cartilage is the interfacial tissue between articulating surfaces, such as bones, and acts as low-friction interfaces. Damage to the lamina splendens, which is the articular cartilage's topmost layer, is an early indicator of joint degradation caused by injury or disease. By gaining comprehensive knowledge on the lamina splendens, particularly its structure and interfacial properties, researchers could enhance the accuracy of human and animal biomechanical models, as well as develop appropriate biomimetic materials for replacing damaged articular cartilage, thereby leading to rational treatment programs for joint disease and injury. Previous studies that utilize light, electron, and force microscopy techniques have found that the lamina splendens is composed of collagen fibers oriented parallel to the cartilage surface and encased in a proteoglycan matrix. Such orientation maximizes wear resistance and proteoglycan retention while promoting the passage of nutrients and synovial fluid. Although the structure of the lamina splendens has been explored in the literature, the low-friction interface of this tissue remains only partially characterized. Various functional models are currently available for the interface, such as pure boundary lubrication, thin films exuded under pressure, and sheets of trapped proteins. Recent studies suggest that each of these lubrication models has certain advantages over one another. Further research is needed to fully model the interface of this tissue. In this review, we summarize the methods for characterizing the lamina splendens and the results of each method. This paper aims to serve as a resource for existing studies to date and a roadmap of the investigations needed to gain further insight into the lamina splendens and the progression of joint disease.

Molecular changes in articular cartilage and subchondral bone in the rat anterior cruciate ligament transection and meniscectomized models of osteoarthritis.

PubMed

Pickarski, Maureen; Hayami, Tadashi; Zhuo, Ya; Duong, Le T

2011-08-24

Osteoarthritis (OA) is a debilitating, progressive joint disease. Similar to the disease progression in humans, sequential events of early cartilage degradation, subchondral osteopenia followed by sclerosis, and late osteophyte formation were demonstrated in the anterior cruciate ligament transection (ACLT) or ACLT with partial medial meniscectomy (ACLT + MMx) rat OA models. We describe a reliable and consistent method to examine the time dependent changes in the gene expression profiles in articular cartilage and subchondral bone. Local regulation of matrix degradation markers was demonstrated by a significant increase in mRNA levels of aggrecanase-1 and MMP-13 as early as the first week post-surgery, and expression remained elevated throughout the 10 week study. Immunohistochemistry confirmed MMP-13 expression in differentiated chondrocytes and synovial fibroblasts at week-2 and cells within osteophytes at week-10 in the surgically-modified-joints. Concomitant increases in chondrocyte differentiation markers, Col IIA and Sox 9, and vascular invasion markers, VEGF and CD31, peaked around week-2 to -4, and returned to Sham levels at later time points in both models. Indeed, VEGF-positive cells were found in the deep articular chondrocytes adjacent to subchondral bone. Osteoclastic bone resorption markers, cathepsin K and TRAP, were also elevated at week-2. Confirming bone resorption is an early local event in OA progression, cathepsin K positive osteoclasts were found invading the articular cartilage from the subchondral region at week 2. This was followed by late disease events, including subchondral sclerosis and osteophyte formation, as demonstrated by the upregulation of the osteoanabolic markers runx2 and osterix, toward week-4 to 6 post-surgery. In summary, this study demonstrated the temporal and cohesive gene expression changes in articular cartilage and subchondral bone using known markers of OA progression. The findings here support genome-wide profiling efforts to elucidate the sequential and complex regulation of the disease.

Effect of Enrofloxacin on Histochemistry, Immunohistochemistry and Molecular Changes in Lamb Articular Cartilage.

PubMed

Khazaeel, Kaveh; Mazaheri, Yazdan; Hashemi Tabar, Mahmood; Najafzadeh, Hossein; Morovvati, Hassan; Ghadrdan, Alireza

2015-01-01

Enrofloxacin is a synthetic chemotherapeutic agent from the class of the fluoroquinolones that is widely used to treat bacterial infections. It is metabolized to ciprofloxacin in the body as active metabolite. Fluoroquinolones change in the articular cartilage, especially with high doses and more than two weeks use. So, due to relatively excessive use of enrofloxacin in mammals and similarity of lambs to human subjects with respect to skeletal activity cycles, this study was done to investigate the effects of enrofloxacin on some cellular and molecular changes in growing lamb articular cartilage to evaluate some possible mechanisms involved these changes. Twelve, 2-month-old male lambs divided into three groups: control group received only normal saline; therapeutic group received 5mg/kg enrofloxacin subcutaneously, daily, for 15 days and toxic group received 35 mg/kg enrofloxacin in the same manner as therapeutic group. Twenty four hours after the last dose, the animals were sacrificed, and their stifle joints were dissected. Sampling from distal femoral and proximal tibial extremities was done quickly for further histological and molecular studies. Collagen-п content was studied with avidin-biotin immunohistochemistry method in different groups. Expression of Sox9 and caspase-3 was evaluated by Real-time PCR. Immunohistochemical changes were included decreases of matrix proteoglycans, carbohydrates, and Collagen-п in the toxic group. Some of these changes were observed in the therapeutic group with less intensity in comparison to the toxic group. Enrofloxacin were significantly decreased (P≤0.05). Sox9 expression in therapeutic and toxic groups compared to control group. But caspase -3 expressions in the toxic group significantly increased (P≤0.0001) with a comparison to other groups, while, between control and therapeutic groups, there were no significant differences. So, it can be concluded that enrofloxacin increases apoptosis in chondrocytes and decreases their numbers. Enrofloxacin use in growing lambs even at recommended therapeutic dose is not completely safe on articular cartilage. Moreover, higher doses of enrofloxacin induce severe changes in lamb articular cartilage.

Basic fibroblast growth factor accelerates matrix degradation via a neuro-endocrine pathway in human adult articular chondrocytes.

PubMed

Im, Hee-Jeong; Li, Xin; Muddasani, Prasuna; Kim, Gun-Hee; Davis, Francesca; Rangan, Jayanthi; Forsyth, Christopher B; Ellman, Michael; Thonar, Eugene J M A

2008-05-01

Pain-related neuropeptides released from synovial fibroblasts, such as substance P, have been implicated in joint destruction. Substance P-induced inflammatory processes are mediated via signaling through a G-protein-coupled receptor, that is, neurokinin-1 tachykinin receptor (NK(1)-R). We determined the pathophysiological link between substance P and its receptor in human adult articular cartilage homeostasis. We further examined if catabolic growth factors such as basic fibroblast growth factor (bFGF or FGF-2) or IL-1beta accelerate matrix degradation via a neural pathway upregulation of substance P and NK(1)-R. We show here that substance P stimulates the production of cartilage-degrading enzymes, such as matrix metalloproteinase-13 (MMP-13), and suppresses proteoglycan deposition in human adult articular chondrocytes via NK(1)-R. Furthermore, we have demonstrated that substance P negates proteoglycan stimulation promoted by bone morphogenetic protein-7, suggesting the dual role of substance P as both a pro-catabolic and anti-anabolic mediator of cartilage homeostasis. We report that bFGF-mediated stimulation of substance P and its receptor NK(1)-R is, in part, through an IL-1beta-dependent pathway. (c) 2007 Wiley-Liss, Inc.

Basic Fibroblast Growth Factor Accelerates Matrix Degradation Via a Neuro-Endocrine Pathway in Human Adult Articular Chondrocytes

PubMed Central

IM, HEE-JEONG; LI, XIN; MUDDASANI, PRASUNA; KIM, GUN-HEE; DAVIS, FRANCESCA; RANGAN, JAYANTHI; FORSYTH, CHRISTOPHER B.; ELLMAN, MICHAEL; THONAR, EUGENE JMA

2010-01-01

Pain-related neuropeptides released from synovial fibroblasts, such as substance P, have been implicated in joint destruction. Substance P-induced inflammatory processes are mediated via signaling through a G-protein-coupled receptor, that is, neurokinin-1 tachykinin receptor (NK1-R). We determined the pathophysiological link between substance P and its receptor in human adult articular cartilage homeostasis. We further examined if catabolic growth factors such as basic fibroblast growth factor (bFGF or FGF-2) or IL-1β accelerate matrix degradation via a neural pathway upregulation of substance P and NK1-R. We show here that substance P stimulates the production of cartilage-degrading enzymes, such as matrix metalloproteinase-13 (MMP-13), and suppresses proteoglycan deposition in human adult articular chondrocytes via NK1-R. Furthermore, we have demonstrated that substance P negates proteoglycan stimulation promoted by bone morphogenetic protein-7, suggesting the dual role of substance P as both a pro-catabolic and anti-anabolic mediator of cartilage homeostasis. We report that bFGF-mediated stimulation of substance P and its receptor NK1-R is, in part, through an IL-1β-dependent pathway. PMID:17960584

Safety of intra-articular transplantation of lentivirally transduced mesenchymal stromal cells for haemophilic arthropathy in a non-human primate.

PubMed

Ohmori, Tsukasa; Mizukami, Hiroaki; Katakai, Yuko; Kawai, Sho; Nakamura, Hitoyasu; Inoue, Makoto; Shu, Tsugumine; Sugimoto, Hideharu; Sakata, Yoichi

2018-05-08

Joint bleeding and resultant arthropathy are major determinants of quality of life in haemophilia patients. We previously developed a mesenchymal stromal cell (MSC)-based treatment approach for haemophilic arthropathy in a mouse model of haemophilia A. Here, we evaluated the long-term safety of intra-articular injection of lentivirally transduced autologous MSCs in non-human primates. Autologous bone-marrow-derived MSCs transduced with a lentiviral vector expressing coagulation factor VIII (FVIII) were injected into the left knee joint of cynomolgus monkeys. We first conducted codon optimization to increase FVIII production in the cells. Lentiviral transduction of autologous MSCs resulted in a significant increase of FVIII in the culture supernatant before transplantation. We did not find any tumour generation around the knee structure at 11-16 months after injection by magnetic resonance imaging. The proviral sequence of the simian immunodeficiency virus lentiviral vector was not detected in the heart, lungs, spleen, liver, testis, or bone marrow by real-time quantitative PCR. We confirmed the long-term safety of intra-articular injection of transduced MSCs in a non-human primate. The procedure may be an attractive therapeutic approach for joint diseases in haemophilia patients.

Bovine lactoferricin induces TIMP-3 via the ERK1/2-Sp1 axis in human articular chondrocytes

PubMed Central

Yan, Dongyao; Chen, Di; Hawse, John R; van Wijnen, Andre J; Im, Hee-Jeong

2013-01-01

Bovine lactoferricin (LfcinB) is a heparan sulfate-binding peptide with multiple bioactivities. In human articular cartilage, LfcinB antagonizes interleukin-1 β (IL-1β) and fibroblast growth factor 2 (FGF-2) in proteoglycan metabolism, catabolic protease expression, and induction of pro-inflammatory mediators. LfcinB specifically activates ERK1/2, p38 and Akt, but whether these signaling pathways control the expression of LfcinB target genes remained unknown. In this report, we characterized a novel aspect of LfcinB-mediated genetic response in human articular chondrocytes, tissue inhibitor of metalloproteinase 3 (TIMP-3) induction. Inhibition of individual signaling pathways revealed that ERK1/2 functions as the major pathway in TIMP-3 expression, whereas Akt plays a minor role. Further investigation identified Sp1 as a critical transcriptional activator in TIMP-3 regulation, and Sp1 activity is modulated by ERK1/2, not Akt. Comparative quantification indicates significant downregulation of TIMP-3 occurs in OA chondrocytes, suggesting a beneficial role of LfcinB in OA pathogenesis. Our results collectively provide new insights into the mechanism of action of LfcinB, and support the candidacy of LfcinB as a chondroprotective agent. PMID:23313877

Mastering the Physical Examination of the Athlete's Hip.

PubMed

Trofa, David P; Mayeux, Sophie E; Parisien, Robert L; Ahmad, Christopher S; Lynch, T Sean

In this review, we describe precise methods for evaluating the athlete's hip or groin with an emphasis on recognizing the most common extra-articular and intra-articular pathologies, including adductor strains, athletic pubalgia, osteitis pubis, and femoroacetabular impingement with labral tears.

Distribution of Basement Membrane Molecules, Laminin and Collagen Type IV, in Normal and Degenerated Cartilage Tissues

PubMed Central

Toh, Wei Seong; Gomoll, Andreas H.; Olsen, Bjørn Reino; Spector, Myron

2014-01-01

Objective: The objective of the present study was to investigate the presence and distribution of 2 basement membrane (BM) molecules, laminin and collagen type IV, in healthy and degenerative cartilage tissues. Design: Normal and degenerated tissues were obtained from goats and humans, including articular knee cartilage, the intervertebral disc, and meniscus. Normal tissue was also obtained from patella-tibial enthesis in goats. Immunohistochemical analysis was performed using anti-laminin and anti–collagen type IV antibodies. Human and goat skin were used as positive controls. The percentage of cells displaying the pericellular presence of the protein was graded semiquantitatively. Results: When present, laminin and collagen type IV were exclusively found in the pericellular matrix, and in a discrete layer on the articulating surface of normal articular cartilage. In normal articular (hyaline) cartilage in the human and goat, the proteins were found co-localized pericellularly. In contrast, in human osteoarthritic articular cartilage, collagen type IV but not laminin was found in the pericellular region. Nonpathological fibrocartilaginous tissues from the goat, including the menisci and the enthesis, were also positive for both laminin and collagen type IV pericellularly. In degenerated fibrocartilage, including intervertebral disc, as in degenerated hyaline cartilage only collagen type IV was found pericellularly around chondrocytes but with less intense staining than in non-degenerated tissue. In calcified cartilage, some cells were positive for laminin but not type IV collagen. Conclusions: We report differences in expression of the BM molecules, laminin and collagen type IV, in normal and degenerative cartilaginous tissues from adult humans and goats. In degenerative tissues laminin is depleted from the pericellular matrix before collagen type IV. The findings may inform future studies of the processes underlying cartilage degeneration and the functional roles of these 2 extracellular matrix proteins, normally associated with BM. PMID:26069692

An ultrasonic measurement for in vitro depth-dependent equilibrium strains of articular cartilage in compression

NASA Astrophysics Data System (ADS)

Zheng, Y. P.; Mak, A. F. T.; Lau, K. P.; Qin, L.

2002-09-01

The equilibrium depth-dependent biomechanical properties of articular cartilage were measured using an ultrasound-compression method. Ten cylindrical bovine patella cartilage-bone specimens were tested in compression followed by a period of force-relaxation. A 50 MHz focused ultrasound beam was transmitted into the cartilage specimen through a remaining bone layer and a small hole at the centre of a specimen platform. The ultrasound echoes reflected or scattered within the articular cartilage were collected using the same transducer. The displacements of the tissues at different depths of the articular cartilage were derived from the ultrasound echo signals recorded during the compression and the subsequent force-relaxation. For two steps of 0.1 mm compression, the average strain at the superficial 0.2 mm thick layer (0.35 +/- 0.09) was significantly (p < 0.05) larger than that at the subsequent 0.2 mm thick layer (0.05 +/- 0.07) and that at deeper layers (0.01 +/- 0.02). It was demonstrated that the compressive biomechanical properties of cartilage were highly depth-dependent. The results suggested that the ultrasound-compression method could be a useful tool for the study of the depth-dependent biomechanical properties of articular cartilage.

Label-free characterization of articular cartilage in osteoarthritis model mice by Raman spectroscopy

NASA Astrophysics Data System (ADS)

Oshima, Yusuke; Akehi, Mayu; Kiyomatsu, Hiroshi; Miura, Hiromasa

2017-02-01

Osteoarthritis (OA) is very common joint disease in the aging population. Main symptom of OA is accompanied by degenerative changes of articular cartilage. Cartilage contains mostly type II collagen and proteoglycans, so it is difficult to access the quality and morphology of cartilage tissue in situ by conventional diagnostic tools (X-ray, MRI and echography) directly or indirectly. Raman spectroscopy is a label-free technique which enables to analyze molecular composition in degenerative cartilage. In this study, we generated an animal OA model surgically induced by knee joint instability, and the femurs were harvested at two weeks after the surgery. We performed Raman spectroscopic analysis for the articular cartilage of distal femurs in OA side and unaffected side in each mouse. In the result, there is no gross findings in the surface of the articular cartilage in OA. On the other hand, Raman spectral data of the articular cartilage showed drastic changes in comparison between OA and control side. The major finding of this study is that the relative intensity of phosphate band (960 cm-1) increases in the degenerative cartilage. This may be the result of exposure of subchondral bone due to thinning of the cartilage layer. In conclusion, Raman spectroscopic technique is sufficient to characterize articular cartilage in OA as a pilot study for Raman application in cartilage degeneration and regeneration using animal models and human subjects.

In vitro determination of biomechanical properties of human articular cartilage in osteoarthritis using multi-parametric MRI

NASA Astrophysics Data System (ADS)

Juras, Vladimir; Bittsansky, Michal; Majdisova, Zuzana; Szomolanyi, Pavol; Sulzbacher, Irene; Gäbler, Stefan; Stampfl, Jürgen; Schüller, Georg; Trattnig, Siegfried

2009-03-01

The objective of this study was to evaluate the correlations between MR parameters and the biomechanical properties of naturally degenerated human articular cartilage. Human cartilage explants from the femoral condyles of patients who underwent total knee replacement were evaluated on a micro-imaging system at 3 T. To quantify glycosaminoglycan (GAG) content, delayed gadolinium-enhanced MRI of the cartilage (dGEMRIC) was used. T2 maps were created by using multi-echo, multi-slice spin echo sequences with six echoes: 15, 30, 45, 60, 75, and 90 ms. Data for apparent diffusion constant (ADC) maps were obtained from pulsed gradient spin echo (PGSE) sequences with five b-values: 10.472, 220.0, 627.0, 452.8, 724.5, and 957.7. MR parameters were correlated with mechanical parameters (instantaneous ( I) and equilibrium ( Eq) modulus and relaxation time ( τ)), and the OA stage of each cartilage specimen was determined by histological evaluation of hematoxylin-eosin stained slices. For some parameters, a high correlation was found: the correlation of T1Gd vs Eq ( r = 0.8095), T1Gd vs I/ Eq ( r = -0.8441) and T1Gd vs τ ( r = 0.8469). The correlation of T2 and ADC with selected biomechanical parameters was not statistically significant. In conclusion, GAG content measured by dGEMRIC is highly related to the selected biomechanical properties of naturally degenerated articular cartilage. In contrast, T2 and ADC were unable to estimate these properties. The results of the study imply that some MR parameters can non-invasively predict the biomechanical properties of degenerated articular cartilage.

Transplantation of transduced chondrocytes protects articular cartilage from interleukin 1-induced extracellular matrix degradation.

PubMed Central

Baragi, V M; Renkiewicz, R R; Jordan, H; Bonadio, J; Hartman, J W; Roessler, B J

1995-01-01

Gene therapy used in the context of delivering a therapeutic gene(s) to chondrocytes offers a new approach for treating chondrocyte-mediated cartilage degradation associated with various human arthropathies including osteoarthritis. In this study, gene delivery to human osteoarthritis chondrocytes in monolayer culture was demonstrated using two adenoviral vectors (Ad.CMVlacZ and Ad.RSVntlacZ) carrying the Escherichia coli beta-galactosidase marker gene, and a third vector (Ad.RSV hIL-1ra) containing the cDNA for human interleukin-1 receptor antagonist. At an moi of 10(3) plaque-forming units/chondrocyte, > 90% of the infected cells stained positive for E. coli beta-galactosidase activity, indicating a high efficiency of transduction. Genetically modified chondrocytes were then transplanted onto the articular surface of osteoarthritic cartilage organ cultures with and without the underlying subchondral bone. Both in situ staining of the cartilage organ cultures for E. coli beta-galactosidase activity and examination by scanning electron microscopy indicated that the transplanted chondrocytes adhered and integrated into the articular surface and continued to express transgenic protein. Chondrocytes transduced with Ad.RSV hIL-1ra and seeded onto the surface of osteoarthritic cartilage secreted high levels of biologically active IL-1 receptor antagonist. The Ad.RSV hIL-1ra-treated cartilage samples were resistant to IL1-induced proteoglycan degradation over 10 d of sustained organ culture. These data demonstrate that transplantation of transduced chondrocytes onto the articular surface protects cartilage from IL-1-induced extracellular matrix degradation. Images PMID:7593634

Intra-articular Recombinant Human Proteoglycan 4 Mitigates Cartilage Damage Following Destabilization of the Medial Meniscus in the Yucatan Minipig

PubMed Central

Waller, Kimberly A.; Chin, Kaitlyn E.; Jay, Gregory D.; Zhang, Ling X.; Teeple, Erin; McAllister, Scott; Badger, Gary J.; Schmidt, Tannin A.; Fleming, Braden C.

2016-01-01

Background Lubricin, or proteoglycan 4 (PRG4), is a glycoprotein responsible for joint boundary lubrication. PRG4 has been previously shown to be down-regulated following traumatic joint injury such as a meniscal tear. There is preliminary evidence suggesting that intra-articular injection of PRG4 post-injury will reduce cartilage damage in rat models of surgically-induced post-traumatic osteoarthritis. Objective To determine the efficacy of intra-articular injection of full length recombinant human lubricin (rhPRG4) for reducing cartilage damage after medial meniscus destabilization (DMM) in a pre-clinical large animal model. Study Design Controlled laboratory study Methods Unilateral DMM was performed in 29 Yucutan minipigs. One week post-DMM, animals received 3 weekly intra-articular injections (3cc/injection): 1) rhPRG4 [1.3mg/ml; n=10], 2) rhPRG4+hyaluronan [1.3mg/ml rhPRG4 and 3mg/ml hyaluronan (~950 kDA); n=10], and 3) phosphate buffered saline [PBS; n=9]. Hind limbs were harvested 26 weeks post-surgery. Cartilage integrity was evaluated using macroscopic (India Ink) and microscopic (Safranin O-fast green and hematoxylin & eosin) scoring systems. Secondary outcomes evaluated using ELISA included PRG4 levels in synovial fluid, CTX-II concentrations in urine and serum, and IL-1β levels in synovial fluid and serum. Results The rhPRG4 group had significantly less macroscopic cartilage damage in the medial tibial plateau compared to the PBS group (p=.002). No difference was found between the rhPRG4+hyaluronan and PBS groups (p=.23). However, no differences in microscopic damage scores were observed between the three groups (p=.70). PRG4 production was elevated in the rhPRG4 group synovial fluid compared to the PBS group (p=.033). The rhPRG4 group presented significantly lower urinary CTX-II levels, but not serum levels, when compared to the PBS (p=.013) and rhPRG4+hyaluronan (p=.011) groups. In serum and synovial fluid, both rhPRG4 (p=.006; p=.017) and rhPRG4+hyaluronan groups (p=.009; p=.03) presented decreased IL-1β levels. Conclusion All groups exhibited significant cartilage degeneration following DMM surgery. However, animals treated with rhPRG4 had the least amount of cartilage damage and less inflammation, providing evidence that intra-articular injections of rhPRG4 may slow the progression of post-traumatic osteoarthritis. Clinical Relevance Patients with meniscal trauma are at high risk for post-traumatic osteoarthritis. This study demonstrates that an intra-articular injection regimen of rhPRG4 may attenuate cartilage damage following meniscal injury. PMID:28129516

Biological approach to treatment of intra-articular proximal tibial fractures with double osteosynthesis.

PubMed

Singh, Saurabh; Patel, Pankaj R; Joshi, Anil Kumar; Naik, Rajnikant N; Nagaraj, Chethan; Kumar, Sudeep

2009-02-01

The treatment of intra-articular proximal tibial fractures is associated with complications, and much conflicting literature exists concerning the treatment of choice. In our study, an attempt has been made to develop an ideal and adequate treatment protocol for these intra-articular fractures. The principle of double osteosynthesis, i.e., lateral minimally invasive plate osteosynthesis (MIPO), was combined with a medial external fixator to treat 22 intra-articular proximal tibial fractures with soft tissue injury with a mean follow-up of 25 months. Superficial pin track infection was observed in one case, and no soft tissue breakdown was noted. Loss of articular reconstruction was reported in one case. Bridging callus was seen at 12 weeks (8 weeks-7 months). The principle of substitution or double osteosynthesis, i.e., lateral MIPO, was combined with a medial external fixator and proved to be a fairly good method of fixation in terms of results and complications.

Biochemical quantification of DNA in human articular and septal cartilage using PicoGreen and Hoechst 33258.

PubMed

McGowan, K B; Kurtis, M S; Lottman, L M; Watson, D; Sah, R L

2002-07-01

To compare two fluorometric assays, utilizing (1) the bisbenzimidazole Hoechst 33258 and (2) PicoGreen, for determining DNA content in human cartilage. Human articular and nasal septal cartilage explants were digested using proteinase K. Portions of sample digest were analysed for intrinsic and dye-enhanced fluorescence with either Hoechst 33258 or PicoGreen. Intrinsic tissue fluorescence in both articular and septal cartilage increased with age and was prominent at wavelengths used for Hoechst 33258 but relatively low at wavelengths used for PicoGreen. The relative contribution of intrinsic fluorescence to total dye-enhanced fluorescence of human cartilage was markedly greater for Hoechst 33258 (19-57%) than for PicoGreen (2-7%). Thus, in many situations, DNA in human cartilage can be assayed using PicoGreen without the need to correct for intrinsic cartilage fluorescence. The enhancement of fluorescence by each dye was found to be specific for DNA, as shown by fluorescence spectra, >90% sensitivity to DNase, and resistance to RNase. In addition, little or no interference was caused by non-DNA tissue components, since DNA caused an equal enhancement in the absence or presence of proteinase K digested human cartilage, once intrinsic cartilage fluorescence was subtracted. PicoGreen was more sensitive for assaying DNA (0.9ng DNA/ml) than Hoechst 33258 (6ng DNA/ml) and can also be used in a microplate reader. PicoGreen can be used in a rapid and sensitive assay to quantify DNA in small samples of human cartilage. Copyright 2002 Published by Elsevier Science Ltd on behalf of OsteoArthritis Research Society International.

Extra-articular osteotomy for malunited unicondylar fractures of the proximal phalanx.

PubMed

Harness, Neil G; Chen, Alvin; Jupiter, Jesse B

2005-05-01

To evaluate an extra-articular osteotomy rather than an intra-articular osteotomy in the treatment of malunited unicondylar fractures of the proximal phalanx. An extra-articular osteotomy was used to correct the deformity resulting from a malunion of a unicondylar fracture of the proximal phalanx in 5 patients. A closing wedge osteotomy that was stabilized with tension band fixation accomplished realignment of the joint. Each patient was evaluated at a minimum of 1 year after surgery for radiographic healing, correction of angulation, digital motion, postoperative complications, current level of pain with motion, and overall satisfaction with the procedure. All of the osteotomies healed by 10 to 12 weeks after surgery with an average angular correction from 25 degrees to 1 degrees . The average proximal interphalangeal joint motion improved to 86 degrees from the preoperative average of 40 degrees , whereas the average total digital motion improved from 154 degrees before surgery to 204 degrees at follow-up evaluation. This method of extra-articular osteotomy for malunited unicondylar fractures of the proximal phalanx is highly reproducible, avoids the risks of intra-articular surgery, and leads to a predictable outcome.

Platelet lysate activates quiescent cell proliferation and reprogramming in human articular cartilage: Involvement of hypoxia inducible factor 1.

PubMed

Nguyen, Van Thi; Cancedda, Ranieri; Descalzi, Fiorella

2018-03-01

The idea of rescuing the body self-repair capability lost during evolution is progressively gaining ground in regenerative medicine. In particular, growth factors and bioactive molecules derived from activated platelets emerged as promising therapeutic agents acting as trigger for repair of tissue lesions and restoration of tissue functions. Aim of this study was to assess the potential of a platelet lysate (PL) for human articular cartilage repair considering its activity on progenitor cells and differentiated chondrocytes. PL induced the re-entry in the cell cycle of confluent, growth-arrested dedifferentiated/progenitor cartilage cells. In a cartilage permissive culture environment, differentiated cells also resumed proliferation after exposure to PL. These findings correlated with an up-regulation of the proliferation/survival pathways ERKs and Akt and with an induction of cyclin D1. In short- and long-term cultures of articular cartilage explants, we observed a release of proliferating chondroprogenitors able to differentiate and form an "in vitro" tissue with properties of healthy articular cartilage. Moreover, in cultured cartilage cells, PL induced a hypoxia-inducible factor (HIF-1) alpha increase, its nuclear relocation and the binding to HIF-1 responsive elements. These events were possibly related to the cell proliferation because the HIF-1 inhibitor acriflavine inhibited HIF-1 binding to HIF-1 responsive elements and cell proliferation. Our study demonstrates that PL induces quiescent cartilage cell activation and proliferation leading to new cartilage formation, identifies PL activated pathways playing a role in these processes, and provides a rationale to the application of PL for therapeutic treatment of damaged articular cartilage. Copyright © 2017 John Wiley & Sons, Ltd.

Development and characteristics of pannus-like soft tissue in osteoarthritic articular surface in rat osteoarthritis model.

PubMed

Duc, P A; Yudoh, K; Masuko, K; Kato, T; Nishioka, K; Nakamura, H

2008-01-01

Pannus is invasive granulation tissue found on the articular cartilage having rheumatoid arthritis (RA). However, pannus-like tissue has also been found in osteoarthritis (OA). Our previous study showed that pannus-like tissue in OA (OA pannus) was frequently found in human OA samples. The purpose of the study is to investigate the development and the characteristics of OA pannus in a rat OA model. Ligaments of the knee joint were transected in Wister rats to induce OA. The knee joints were removed at weeks 1, 2, 4 and 6, and subjected to histological study. Samples were stained with hematoxylin and eosin (HE), Safranin-O and immuno-stained for vimentin, CD34, type II collagen and MMP-3. The whole knee joint of OA rats was implanted in SCID mice and kept for a further 3 weeks. Then the histological findings were evaluated in HE sections. OA pannus appeared at week 2 and extend over the articular surface. OA pannus cells were positive for vimentin and/or CD34. At week 6, a part of articular surface was restored with matrix. OA pannus cells expressed MMP-3 as well as type II collagen. Histological study of rat OA knees implanted in SCID mice showed that OA pannus cells filled the joint space and invaded articular cartilage. The presence of OA pannus was found in a rat OA model and its features were similar to those in human OA. OA pannus had both catabolic and reparative features, and the latter feature were speculated to be dominant in the later phase of the disease under a certain environmental condition.

Airflow accelerates bovine and human articular cartilage drying and chondrocyte death.

PubMed

Paterson, S I; Amin, A K; Hall, A C

2015-02-01

Exposure of articular cartilage to static air results in changes to the extracellular matrix (ECM) and stimulates chondrocyte death, which may cause joint degeneration. However during open orthopaedic surgery, cartilage is often exposed to laminar airflow, which may exacerbate these damaging effects. We compared drying in static and moving air in terms of cartilage appearance, hydration and chondrocyte viability, and tested the ability of saline-saturated gauze to limit the detrimental effects of air exposure. Articular cartilage from bovine metatarsophalangeal joints (N = 50) and human femoral heads (N = 6) was exposed for 90 min to (1) static air (2) airflow (up to 0.34 m/s), or (3) airflow (0.18 m/s), covered with gauze. Following air exposure, cartilage was also rehydrated (0.9% saline; 120 min) to determine the reversibility of drying effects. The influence of airflow was assessed by studying macroscopic appearance, and quantifying superficial zone (SZ) chondrocyte viability and cartilage hydration. Airflow caused advanced changes to cartilage appearance, accelerated chondrocyte death, and increased dehydration compared to static air. These effects were prevented if cartilage was covered by saline-saturated gauze. Cartilage rehydration reversed macroscopic changes associated with drying but the chondrocyte death was not altered. Chondrocytes at the cut edge of cartilage were more sensitive to drying compared to cells distant from the edge. Airflow significantly increased articular cartilage dehydration and chondrocyte death compared to static air. As laminar airflow is routinely utilised in operating theatres, it is essential that articular cartilage is kept wet via irrigation or by covering with saline-saturated gauze to prevent chondrocyte death. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

The Regulatory Role of Signaling Crosstalk in Hypertrophy of MSCs and Human Articular Chondrocytes.

PubMed

Zhong, Leilei; Huang, Xiaobin; Karperien, Marcel; Post, Janine N

2015-08-14

Hypertrophic differentiation of chondrocytes is a main barrier in application of mesenchymal stem cells (MSCs) for cartilage repair. In addition, hypertrophy occurs occasionally in osteoarthritis (OA). Here we provide a comprehensive review on recent literature describing signal pathways in the hypertrophy of MSCs-derived in vitro differentiated chondrocytes and chondrocytes, with an emphasis on the crosstalk between these pathways. Insight into the exact regulation of hypertrophy by the signaling network is necessary for the efficient application of MSCs for articular cartilage repair and for developing novel strategies for curing OA. We focus on articles describing the role of the main signaling pathways in regulating chondrocyte hypertrophy-like changes. Most studies report hypertrophic differentiation in chondrogenesis of MSCs, in both human OA and experimental OA. Chondrocyte hypertrophy is not under the strict control of a single pathway but appears to be regulated by an intricately regulated network of multiple signaling pathways, such as WNT, Bone morphogenetic protein (BMP)/Transforming growth factor-β (TGFβ), Parathyroid hormone-related peptide (PTHrP), Indian hedgehog (IHH), Fibroblast growth factor (FGF), Insulin like growth factor (IGF) and Hypoxia-inducible factor (HIF). This comprehensive review describes how this intricate signaling network influences tissue-engineering applications of MSCs in articular cartilage (AC) repair, and improves understanding of the disease stages and cellular responses within an OA articular joint.

The Regulatory Role of Signaling Crosstalk in Hypertrophy of MSCs and Human Articular Chondrocytes

PubMed Central

Zhong, Leilei; Huang, Xiaobin; Karperien, Marcel; Post, Janine N.

2015-01-01

Hypertrophic differentiation of chondrocytes is a main barrier in application of mesenchymal stem cells (MSCs) for cartilage repair. In addition, hypertrophy occurs occasionally in osteoarthritis (OA). Here we provide a comprehensive review on recent literature describing signal pathways in the hypertrophy of MSCs-derived in vitro differentiated chondrocytes and chondrocytes, with an emphasis on the crosstalk between these pathways. Insight into the exact regulation of hypertrophy by the signaling network is necessary for the efficient application of MSCs for articular cartilage repair and for developing novel strategies for curing OA. We focus on articles describing the role of the main signaling pathways in regulating chondrocyte hypertrophy-like changes. Most studies report hypertrophic differentiation in chondrogenesis of MSCs, in both human OA and experimental OA. Chondrocyte hypertrophy is not under the strict control of a single pathway but appears to be regulated by an intricately regulated network of multiple signaling pathways, such as WNT, Bone morphogenetic protein (BMP)/Transforming growth factor-β (TGFβ), Parathyroid hormone-related peptide (PTHrP), Indian hedgehog (IHH), Fibroblast growth factor (FGF), Insulin like growth factor (IGF) and Hypoxia-inducible factor (HIF). This comprehensive review describes how this intricate signaling network influences tissue-engineering applications of MSCs in articular cartilage (AC) repair, and improves understanding of the disease stages and cellular responses within an OA articular joint. PMID:26287176

Bovine lactoferricin is anti-inflammatory and anti-catabolic in human articular cartilage and synovium.

PubMed

Yan, Dongyao; Chen, Di; Shen, Jie; Xiao, Guozhi; van Wijnen, Andre J; Im, Hee-Jeong

2013-02-01

Bovine lactoferricin (LfcinB) is a multi-functional peptide derived from proteolytic cleavage of bovine lactoferrin. LfcinB was found to antagonize the biological effects mediated by angiogenic growth factors such as vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF-2) in endothelial cells. However, the effect of LfcinB on human articular cartilage remained unknown. Here, our findings demonstrate that LfcinB restored the proteoglycan loss promoted by catabolic factors (interleukin-1β) IL-1β and FGF-2 in vitro and ex vivo. Mechanistically, LfcinB attenuated the effects of IL-1β and FGF-2 on the expression of cartilage-degrading enzymes (MMP-1, MMP-3, and MMP-13), destructive cytokines (IL-1β and IL-6), and inflammatory mediators (iNOS and TLR2). LfcinB induced protective cytokine expression (IL-4 and IL-10), and downregulated aggrecanase basal expression. LfcinB specifically activated ERK MAPK and Akt signaling pathways, which may account for its anti-inflammatory activity. We also revealed that LfcinB exerted similar protective effects on human synovial fibroblasts challenged by IL-1β, with minimal cytotoxicity. Collectively, our results suggest that LfcinB possesses potent anti-catabolic and anti-inflammatory bioactivities in human articular tissues, and may be utilized for the prevention and/or treatment of OA in the future. Copyright © 2012 Wiley Periodicals, Inc.

Bovine lactoferricin, an antimicrobial peptide, is anti-inflammatory and anti-catabolic in human articular cartilage and synovium

PubMed Central

Yan, Dongyao; Chen, Di; Shen, Jie; Xiao, Guozhi; van Wijnen, Andre J; Im, Hee-Jeong

2012-01-01

Bovine lactoferricin (LfcinB) is a multi-functional peptide derived from proteolytic cleavage of bovine lactoferrin. LfcinB was found to antagonize the biological effects mediated by angiogenic growth factors such as vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF-2) in endothelial cells. However, the effect of LfcinB on human articular cartilage remained unknown. Here, our findings demonstrate that LfcinB restored the proteoglycan loss promoted by catabolic factors (interleukin-1 β) IL-1β and FGF-2 in vitro and ex vivo. Mechanistically, LfcinB attenuated the effects of IL-1β and FGF-2 on the expression of cartilage-degrading enzymes (MMP-1, MMP-3, and MMP-13), destructive cytokines (IL-1β and IL-6), and inflammatory mediators (iNOS and TLR2). LfcinB induced protective cytokine expression (IL-4 and IL-10), and downregulated aggrecanase basal expression. LfcinB specifically activated ERK MAPK and Akt signaling pathways, which may account for its anti-inflammatory activity. We also revealed that LfcinB exerted similar protective effects on human synovial fibroblasts challenged by IL-1β, with minimal cytotoxicity. Collectively, our results suggest that LfcinB possesses potent anti-catabolic and anti-inflammatory bioactivities in human articular tissues, and may be utilized for the prevention and/or treatment of OA in the future. PMID:22740381

The safety of peri-articular local anaesthetic injection for patients undergoing total knee replacement with autologous blood transfusion: a randomised trial.

PubMed

Wallace, D F; Emmett, S R; Kang, K K; Chahal, G S; Hiskens, R; Balasubramanian, S; McGuinness, K; Parsons, H; Achten, J; Costa, M L

2012-12-01

Intra-operative, peri-articular injection of local anaesthesia is an increasingly popular way of controlling pain following total knee replacement. At the same time, the problems associated with allogenic blood transfusion have led to interest in alternative methods for managing blood loss after total knee replacement, including the use of auto-transfusion of fluid from the patient's surgical drain. It is safe to combine peri-articular infiltration with auto-transfusion from the drain. We performed a randomised clinical trial to compare the concentration of local anaesthetic in the blood and in the fluid collected in the knee drain in patients having either a peri-articular injection or a femoral nerve block. Clinically relevant concentrations of local anaesthetic were found in the fluid from the drains of patients having peri-articular injections (4.92 μg/ml (sd 3.151)). However, none of the patients having femoral nerve blockade had detectable levels. None of the patients in either group had clinically relevant concentrations of local anaesthetic in their blood after re-transfusion. The evidence from this study suggests that it is safe to use peri-articular injection in combination with auto-transfusion of blood from peri-articular drains during knee replacement surgery.

Biomechanics of the natural, arthritic, and replaced human ankle joint

PubMed Central

2014-01-01

The human ankle joint complex plays a fundamental role in gait and other activities of daily living. At the same time, it is a very complicated anatomical system but the large literature of experimental and modelling studies has not fully described the coupled joint motion, position and orientation of the joint axis of rotation, stress and strain in the ligaments and their role in guiding and stabilizing joint motion, conformity and congruence of the articular surfaces, patterns of contact at the articular surfaces, patterns of rolling and sliding at the joint surfaces, and muscle lever arm lengths. The present review article addresses these issues as described in the literature, reporting the most recent relevant findings. PMID:24499639

Effects of C5/C6 Intervertebral Space Distraction Height on Pressure on the Adjacent Intervertebral Disks and Articular Processes and Cervical Vertebrae Range of Motion.

PubMed

Lu, Tingsheng; Luo, Chunshan; Ouyang, Beiping; Chen, Qiling; Deng, Zhongliang

2018-04-25

BACKGROUND This study aimed to investigate the association between range of motion of the cervical vertebrae and various C5/C6 intervertebral space distraction heights. MATERIAL AND METHODS The cervical vertebrae from 6 fresh adult human cadavers were used to prepare the models. Changes in C4/C5 and C6/C7 intervertebral disk pressures, articular process pressure, and range of motion of the cervical vertebrae before and after the distraction of the C5/C6 intervertebral space at benchmark heights of 100%, 120%, 140%, and 160% were tested under different exercise loads. RESULTS The pressure on the adjacent intervertebral disks was highest with the standing upright position before distraction, varied with different positions of the specimens and distraction heights after distraction, and was closest to that before distraction at a distraction height of 120% (P<0.05). The pressure of the adjacent articular processes was highest with left and right rotations before distraction, varied with different positions of the specimens and distraction heights after distraction, and was lowest under the same exercise load with different positions at a distraction height of 120% (P<0.05). The ranges of motion of the cervical vertebrae and intervertebral disks were largest without distraction and at a distraction height of 120% after distraction, respectively (P<0.05). CONCLUSIONS When removing the C5/C6 intervertebral disk and implanting an intervertebral bone graft, a benchmark height of 120% had little influence on the pressure of the adjacent intervertebral disks and articular processes and range of motion of the cervical vertebrae and is therefore an appropriate intervertebral space distraction height.

Effects of C5/C6 Intervertebral Space Distraction Height on Pressure on the Adjacent Intervertebral Disks and Articular Processes and Cervical Vertebrae Range of Motion

PubMed Central

Lu, Tingsheng; Luo, Chunshan; Ouyang, Beiping; Chen, Qiling

2018-01-01

Background This study aimed to investigate the association between range of motion of the cervical vertebrae and various C5/C6 intervertebral space distraction heights. Material/Methods The cervical vertebrae from 6 fresh adult human cadavers were used to prepare the models. Changes in C4/C5 and C6/C7 intervertebral disk pressures, articular process pressure, and range of motion of the cervical vertebrae before and after the distraction of the C5/C6 intervertebral space at benchmark heights of 100%, 120%, 140%, and 160% were tested under different exercise loads. Results The pressure on the adjacent intervertebral disks was highest with the standing upright position before distraction, varied with different positions of the specimens and distraction heights after distraction, and was closest to that before distraction at a distraction height of 120% (P<0.05). The pressure of the adjacent articular processes was highest with left and right rotations before distraction, varied with different positions of the specimens and distraction heights after distraction, and was lowest under the same exercise load with different positions at a distraction height of 120% (P<0.05). The ranges of motion of the cervical vertebrae and intervertebral disks were largest without distraction and at a distraction height of 120% after distraction, respectively (P<0.05). Conclusions When removing the C5/C6 intervertebral disk and implanting an intervertebral bone graft, a benchmark height of 120% had little influence on the pressure of the adjacent intervertebral disks and articular processes and range of motion of the cervical vertebrae and is therefore an appropriate intervertebral space distraction height. PMID:29693646

Lumbar facet anatomy changes in spondylolysis: a comparative skeletal study

PubMed Central

Dar, Gali; Peleg, Smadar; Steinberg, Nili; Alperovitch-Najenson, Dvora; Salame, Khalil; Hershkovitz, Israel

2007-01-01

Opinions differ as to the exact mechanism responsible for spondylolysis (SP) and whether individuals with specific morphological characteristics of the lumbar vertebral neural arch are predisposed to SP. The aim of our study was to reveal the association between SP and the architecture of lumbar articular facets and the inter-facet region. Methods: Using a Microscribe three-dimensional apparatus (Immersion Co., San Jose, CA, USA), length, width and depth of all articular facets and all inter-facet distances in the lumbar spine (L1–L5) were measured. From the Hamann-Todd Human Osteological Collection (Cleveland Museum of Natural History, OH, USA) 120 normal male skeletons with lumbar spines in the control group and 115 with bilateral SP at L5 were selected. Analysis of variance was employed to examine the differences between spondylolytic and normal spines. Results: Three profound differences between SP and the norm appeared: (1) in individuals with SP, the size and shape of L4’s neural arch had significantly greater inter-facet widths, significantly shorter inter-facet heights and significantly shorter and narrower articular facets; (2) only in the L4 vertebra in individuals with SP was the inferior inter-facet width greater in size than the superior inter-facet width of the vertebra below (L5) (38.7 mm versus 40 mm); (3) in all lumbar vertebrae, the right inferior articular facets in individuals with SP were flatter compared to the control group. Conclusions: Individuals with L4 “SP” characteristics are at a greater risk of developing fatigue fractures in the form of spondylolysis at L5. PMID:17440753

Reconstruction of Hyaline Cartilage Deep Layer Properties in 3-Dimensional Cultures of Human Articular Chondrocytes.

PubMed

Nanduri, Vibudha; Tattikota, Surendra Mohan; T, Avinash Raj; Sriramagiri, Vijaya Rama Rao; Kantipudi, Suma; Pande, Gopal

2014-06-01

Articular cartilage (AC) injuries and malformations are commonly noticed because of trauma or age-related degeneration. Many methods have been adopted for replacing or repairing the damaged tissue. Currently available AC repair methods, in several cases, fail to yield good-quality long-lasting results, perhaps because the reconstructed tissue lacks the cellular and matrix properties seen in hyaline cartilage (HC). To reconstruct HC tissue from 2-dimensional (2D) and 3-dimensional (3D) cultures of AC-derived human chondrocytes that would specifically exhibit the cellular and biochemical properties of the deep layer of HC. Descriptive laboratory study. Two-dimensional cultures of human AC-derived chondrocytes were established in classical medium (CM) and newly defined medium (NDM) and maintained for a period of 6 weeks. These cells were suspended in 2 mm-thick collagen I gels, placed in 24-well culture inserts, and further cultured up to 30 days. Properties of chondrocytes, grown in 2D cultures and the reconstructed 3D cartilage tissue, were studied by optical and scanning electron microscopic techniques, immunohistochemistry, and cartilage-specific gene expression profiling by reverse transcription polymerase chain reaction and were compared with those of the deep layer of native human AC. Two-dimensional chondrocyte cultures grown in NDM, in comparison with those grown in CM, showed more chondrocyte-specific gene activity and matrix properties. The NDM-grown chondrocytes in 3D cultures also showed better reproduction of deep layer properties of HC, as confirmed by microscopic and gene expression analysis. The method used in this study can yield cartilage tissue up to approximately 1.6 cm in diameter and 2 mm in thickness that satisfies the very low cell density and matrix composition properties present in the deep layer of normal HC. This study presents a novel and reproducible method for long-term culture of AC-derived chondrocytes and reconstruction of cartilage tissue with properties similar to the deep layer of HC in vitro. The HC tissue obtained by the method described can be used to develop an implantable product for the replacement of damaged or malformed AC, especially in younger patients where the lesions are caused by trauma or mechanical stress.

The intra-articular pressure of the shoulder: an experimental study on the role of the glenoid labrum in stabilizing the joint.

PubMed

Habermeyer, P; Schuller, U; Wiedemann, E

1992-01-01

It was shown on human corpses that the glenohumeral joint may be compared to a piston surrounded by a valve. The glenoid labrum, then, should work like the valve block, sealing the joint from atmospheric pressure. In order to test this hypothesis, 18 human shoulder preparations were studied. The mean stabilizing force obtained by atmospheric pressure was 146 N. Additionally, 15 patients without any sign of instability and 17 patients with an anterior instability of the shoulder were tested under general anesthesia. In stable shoulder joints, traction at the arm caused negative intra-articular pressure that could be correlated to the amount of force exerted. In contrast, unstable shoulder joints with a tear of the glenoid labrum (Bankart lesion) did not exhibit this phenomenon. For unstable shoulder joints, the piston-and-valve model is no longer valid. This enlarges the current concept of shoulder joint stability in two ways: (a) the absence of negative intra-articular pressure disturbs joint mechanics and (b) altered pressure receptors might disturb motor coordination that dynamically protects the shoulder from dislocating forces.

Changes in muscle and joint coordination in learning to direct forces.

PubMed

Hasson, Christopher J; Caldwell, Graham E; van Emmerik, Richard E A

2008-08-01

While it has been suggested that bi-articular muscles have a specialized role in directing external reaction forces, it is unclear how humans learn to coordinate mono- and bi-articular muscles to perform force-directing tasks. Participants were asked to direct pedal forces in a specified target direction during one-legged cycling. We expected that with practice, performance improvement would be associated with specific changes in joint torque patterns and mono- and bi-articular muscular coordination. Nine male participants practiced pedaling an ergometer with only their left leg, and were instructed to always direct their applied pedal force perpendicular to the crank arm (target direction) and to maintain a constant pedaling speed. After a single practice session, the mean error between the applied and target pedal force directions decreased significantly. This improved performance was accompanied by a significant decrease in the amount of ankle angular motion and a smaller increase in knee and hip angular motion. This coincided with a re-organization of lower extremity joint torques, with a decrease in ankle plantarflexor torque and an increase in knee and hip flexor torques. Changes were seen in both mono- and bi-articular muscle activity patterns. The mono-articular muscles exhibited greater alterations, and appeared to contribute to both mechanical work and force-directing. With practice, a loosening of the coupling between bi-articular thigh muscle activation and joint torque co-regulation was observed. The results demonstrated that participants were able to learn a complex and dynamic force-directing task by changing the direction of their applied pedal forces through re-organization of joint torque patterns and mono- and bi-articular muscle coordination.

A fast quadrature-based numerical method for the continuous spectrum biphasic poroviscoelastic model of articular cartilage.

PubMed

Stuebner, Michael; Haider, Mansoor A

2010-06-18

A new and efficient method for numerical solution of the continuous spectrum biphasic poroviscoelastic (BPVE) model of articular cartilage is presented. Development of the method is based on a composite Gauss-Legendre quadrature approximation of the continuous spectrum relaxation function that leads to an exponential series representation. The separability property of the exponential terms in the series is exploited to develop a numerical scheme that can be reduced to an update rule requiring retention of the strain history at only the previous time step. The cost of the resulting temporal discretization scheme is O(N) for N time steps. Application and calibration of the method is illustrated in the context of a finite difference solution of the one-dimensional confined compression BPVE stress-relaxation problem. Accuracy of the numerical method is demonstrated by comparison to a theoretical Laplace transform solution for a range of viscoelastic relaxation times that are representative of articular cartilage. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Nondestructive imaging of fiber structure in articular cartilage using optical polarization tractography

NASA Astrophysics Data System (ADS)

Yao, Xuan; Wang, Yuanbo; Ravanfar, Mohammadreza; Pfeiffer, Ferris M.; Duan, Dongsheng; Yao, Gang

2016-11-01

Collagen fiber orientation plays an important role in determining the structure and function of the articular cartilage. However, there is currently a lack of nondestructive means to image the fiber orientation from the cartilage surface. The purpose of this study is to investigate whether the newly developed optical polarization tractography (OPT) can image fiber structure in articular cartilage. OPT was applied to obtain the depth-dependent fiber orientation in fresh articular cartilage samples obtained from porcine phalanges. For comparison, we also obtained collagen fiber orientation in the superficial zone of the cartilage using the established split-line method. The direction of each split-line was quantified using image processing. The orientation measured in OPT agreed well with those obtained from the split-line method. The correlation analysis of a total of 112 split-lines showed a greater than 0.9 coefficient of determination (R2) between the split-line results and OPT measurements obtained between 40 and 108 μm in depth. In addition, the thickness of the superficial layer can also be assessed from the birefringence images obtained in OPT. These results support that OPT provides a nondestructive way to image the collagen fiber structure in articular cartilage. This technology may be valuable for both basic cartilage research and clinical orthopedic applications.

The human first carpometacarpal joint: osteoarthritic degeneration and 3-dimensional modeling.

PubMed

Kovler, Maksim; Lundon, Katie; McKee, Nancy; Agur, Anne

2004-01-01

The purpose of this study was to gain insight into potential mechanical factors contributing to osteoarthritis of the human first carpometacarpal joint (CMC). This was accomplished by creating three-dimensional (3-D) computer models of the articular surfaces of CMC joints of older humans and by determining their locus of cartilage degeneration. The research questions of this study were: 1) What is the articular wear pattern of cartilage degeneration in CMC osteoarthritis?, (2) Are there significant topographic differences in joint area and contour between the joints of males and females?, and 3) Are there measurable bony joint recesses consistently found within the joint? The articular surfaces of 25 embalmed cadaveric joints (from 13 cadavers) were graded for degree of osteoarthritis, and the location of degeneration was mapped using a dissection microscope. The surfaces of 14 mildly degenerated joints were digitized and reconstructed as 3-D computer models using the Microscribe 3D-X Digitizer and the Rhinoceros 2.0 NURBS Modeling Software. This technology provided accurate and reproducible information on joint area and topography. The dorsoradial trapezial region was found to be significantly more degenerated than other quadrants in both males and females. Mean trapezial articular surface area was 197 mm 2 in males and 160 mm(2) in females; the respective mean areas for the metacarpal were 239 mm(2) in males and 184 mm(2) in females. Joints of females were found to be significantly more concave in radioulnar profile than those of males. Three bony joint recesses were consistently found, two in the radial and ulnar aspects of the trapezium and the third in the palmar surface of the metacarpal.

Aging and oxidative stress reduce the response of human articular chondrocytes to insulin-like growth factor 1 and osteogenic protein 1.

PubMed

Loeser, Richard F; Gandhi, Uma; Long, David L; Yin, Weihong; Chubinskaya, Susan

2014-08-01

To determine the effects of aging and oxidative stress on the response of human articular chondrocytes to insulin-like growth factor 1 (IGF-1) and osteogenic protein 1 (OP-1). Chondrocytes isolated from normal articular cartilage obtained from tissue donors were cultured in alginate beads or monolayer. Cells were stimulated with 50-100 ng/ml of IGF-1, OP-1, or both. Oxidative stress was induced using tert-butyl hydroperoxide. Sulfate incorporation was used to measure proteoglycan synthesis, and immunoblotting of cell lysates was performed to analyze cell signaling. Confocal microscopy was performed to measure nuclear translocation of Smad4. Chondrocytes isolated from the articular cartilage of tissue donors ranging in age from 24 years to 81 years demonstrated an age-related decline in proteoglycan synthesis stimulated by IGF-1 and IGF-1 plus OP-1. Induction of oxidative stress inhibited both IGF-1- and OP-1-stimulated proteoglycan synthesis. Signaling studies showed that oxidative stress inhibited IGF-1-stimulated Akt phosphorylation while increasing phosphorylation of ERK, and that these effects were greater in cells from older donors. Oxidative stress also increased p38 phosphorylation, which resulted in phosphorylation of Smad1 at the Ser(206) inhibitory site and reduced nuclear accumulation of Smad1. Oxidative stress also modestly reduced OP-1-stimulated nuclear translocation of Smad4. These results demonstrate an age-related reduction in the response of human chondrocytes to IGF-1 and OP-1, which are 2 important anabolic factors in cartilage, and suggest that oxidative stress may be a contributing factor by altering IGF-1 and OP-1 signaling. Copyright © 2014 by the American College of Rheumatology.

Elastic coupling of limb joints enables faster bipedal walking

PubMed Central

Dean, J.C.; Kuo, A.D.

2008-01-01

The passive dynamics of bipedal limbs alone are sufficient to produce a walking motion, without need for control. Humans augment these dynamics with muscles, actively coordinated to produce stable and economical walking. Present robots using passive dynamics walk much slower, perhaps because they lack elastic muscles that couple the joints. Elastic properties are well known to enhance running gaits, but their effect on walking has yet to be explored. Here we use a computational model of dynamic walking to show that elastic joint coupling can help to coordinate faster walking. In walking powered by trailing leg push-off, the model's speed is normally limited by a swing leg that moves too slowly to avoid stumbling. A uni-articular spring about the knee allows faster but uneconomical walking. A combination of uni-articular hip and knee springs can speed the legs for improved speed and economy, but not without the swing foot scuffing the ground. Bi-articular springs coupling the hips and knees can yield high economy and good ground clearance similar to humans. An important parameter is the knee-to-hip moment arm that greatly affects the existence and stability of gaits, and when selected appropriately can allow for a wide range of speeds. Elastic joint coupling may contribute to the economy and stability of human gait. PMID:18957360

Bovine lactoferricin induces TIMP-3 via the ERK1/2-Sp1 axis in human articular chondrocytes.

PubMed

Yan, Dongyao; Chen, Di; Hawse, John R; van Wijnen, Andre J; Im, Hee-Jeong

2013-03-15

Bovine lactoferricin (LfcinB) is a heparan sulfate-binding peptide with multiple bioactivities. In human articular cartilage, LfcinB antagonizes interleukin-1 β (IL-1β) and fibroblast growth factor 2 (FGF-2) in proteoglycan metabolism, catabolic protease expression, and induction of pro-inflammatory mediators. LfcinB specifically activates ERK1/2, p38 and Akt, but whether these signaling pathways control the expression of LfcinB target genes remained unknown. In this report, we characterized a novel aspect of LfcinB-mediated genetic response in human articular chondrocytes, tissue inhibitor of metalloproteinase 3 (TIMP-3) induction. Inhibition of individual signaling pathways revealed that ERK1/2 functions as the major pathway in TIMP-3 expression, whereas Akt plays a minor role. Further investigation identified Sp1 as a critical transcriptional activator in TIMP-3 regulation, and Sp1 activity is modulated by ERK1/2, not Akt. Comparative quantification indicates that significant downregulation of TIMP-3 occurs in OA chondrocytes, suggesting a beneficial role of LfcinB in OA pathogenesis. Our results collectively provide new insights into the mechanism of action of LfcinB, and support the candidacy of LfcinB as a chondroprotective agent. Copyright © 2013 Elsevier B.V. All rights reserved.

Articular Chondrocytes Express the Receptor for Advanced Glycation End Products

PubMed Central

Loeser, Richard F.; Yammani, Raghunatha R.; Carlson, Cathy S.; Chen, Hong; Cole, Ada; Im, Hee-Jeong; Bursch, Laura S.; Yan, Shi Du

2006-01-01

Objective The receptor for advanced glycation end products (RAGE) binds multiple ligands, including S100 proteins, high mobility group box chromosomal protein 1 (HMGB-1), and AGEs, all of which are present in articular cartilage. Stimulation of RAGE signaling can lead to MAP kinase activation and increased NF-κB activity. The objective of the present study was to determine if chondrocytes express functional RAGE. Methods The presence of chondrocyte RAGE was analyzed by immunohistochemistry using normal and osteoarthritic (OA) cartilage from young and old monkeys and humans, immunoblotting of chondrocyte lysates and human cartilage extracts, and reverse transcription–polymerase chain reaction (RT-PCR) analysis of RNA from chondrocytes treated with interleukin-1 (IL-1) and fibronectin fragments. RAGE signaling was evaluated by stimulating chondrocytes with S100B and HMGB-1 and analyzing for activation of the ERK MAP kinase and NF-κB. The ability of S100B and HMGB-1 to stimulate matrix metalloproteinase 13 (MMP-13) production was also assessed. A pull-down assay using biotin-labeled S100B was used to demonstrate binding to RAGE. Results RAGE was detected in sections of monkey knee cartilage and human knee and ankle cartilage. Increased immunostaining for RAGE was noted in cartilage from older adult monkeys and humans and was further increased in OA tissue. RAGE was also detected by immunoblotting and by RT-PCR, where IL-1β and fibronectin fragments were found to stimulate RAGE expression. Stimulation of chondrocytes with S100B or HMGB-1 increased phosphorylation of the ERK MAP kinase and the p65 subunit of NF-κB and increased the production of MMP-13. This signaling was inhibited in cells pretreated with soluble RAGE, and S100B was shown to bind to chondrocyte RAGE. Conclusion Articular chondrocytes express functional RAGE. The increase in RAGE noted in OA cartilage and the ability of RAGE ligands to stimulate chondrocyte MAP kinase and NF-κB activity and to stimulate MMP-13 production suggests that chondrocyte RAGE signaling could play a role in OA. PMID:16052547

Intra-articular Enzyme Replacement Therapy with rhIDUA is Safe, Well-Tolerated, and Reduces Articular GAG Storage in the Canine Model of Mucopolysaccharidosis Type I

PubMed Central

Wang, Raymond Y; Aminian, Afshin; McEntee, Michael F; Kan, Shih-Hsin; Simonaro, Calogera M; Lamanna, William; Lawrence, Roger; Ellinwood, N. Matthew; Guerra, Catalina; Le, Steven Q; Dickson, Patricia I; Esko, Jeffrey D

2014-01-01

Background Treatment with intravenous enzyme replacement therapy and hematopoietic stem cell transplantation for mucopolysaccharidosis (MPS) type I does not address joint disease, resulting in persistent orthopedic complications and impaired quality of life. A proof-of-concept study was conducted to determine the safety, tolerability, and efficacy of intra-articular recombinant human iduronidase (IA-rhIDUA) enzyme replacement therapy in the canine MPS I model. Methods Four MPS I dogs underwent monthly rhIDUA injections (0.58 mg/joint) into the right elbow and knee for six months. Contralateral elbows and knees concurrently received normal saline. No intravenous rhIDUA therapy was administered. Monthly blood counts, chemistries, anti-rhIDUA antibody titers, and synovial fluid cell counts were measured. Lysosomal storage of synoviocytes and chondrocytes, synovial macrophages and plasma cells were scored at baseline and one month following the final injection. Results All injections were well-tolerated without adverse reactions. One animal required prednisone for spinal cord compression. There were no clinically significant abnormalities in blood counts or chemistries. Circulating anti-rhIDUA antibody titers gradually increased in all dogs except the prednisone-treated dog; plasma cells, which were absent in all baseline synovial specimens, were predominantly found in synovium of rhIDUA-treated joints at study-end. Lysosomal storage in synoviocytes and chondrocytes following 6 months of IA-rhIDUA demonstrated significant reduction compared to tissues at baseline, and saline-treated tissues at study-end. Mean joint synovial GAG levels in IA-rhIDUA joints was 8.62±5.86 μg/mg dry weight and 21.6±10.4 μg/mg dry weight in control joints (60% reduction). Cartilage heparan sulfate was also reduced in the IA-rhIDUA joints (113±39.5 ng/g wet weight) compared to saline-treated joints (142±56.4 ng/g wet weight). Synovial macrophage infiltration, which was present in all joints at baseline, was abolished in rhIDUA-treated joints only. Conclusions Intra-articular rhIDUA is well-tolerated and safe in the canine MPS I animal model. Qualitative and quantitative assessments indicate that IA-rhIDUA successfully reduces tissue and cellular GAG storage in synovium and articular cartilage, including cartilage deep to the articular surface, and eliminates inflammatory macrophages from synovial tissue. PMID:24951454

Role of platelet-rich plasma in articular cartilage injury and disease.

PubMed

Mascarenhas, Randy; Saltzman, Bryan M; Fortier, Lisa A; Cole, Brian J

2015-02-01

Clinical and laboratory research aimed at biological approaches to cartilage repair are currently in high demand due to the poor regenerative capacity of articular cartilage in the setting of a diseased articular environment. Platelet-rich plasma (PRP) takes advantage of supraphysiological concentrations of platelets and their growth factors harbored in α-granules, which together attempt to return the diseased articular cartilage to a preinjury state. The local use of PRP directly at the site of cartilage injury is thought to stimulate a natural healing cascade and accelerate the formation of cartilage repair tissue. This article provides an overview of the basic science behind the use of PRP in the treatment of cartilage injury and disease. Both initial and current examples of the use of intra-articular PRP in clinical human studies are provided. These include the use of PRP either alone or as an augmentation device with various other procedures, including arthroscopic microfracture and cell-free resorbable polyglycolic acid-hyaluronan implantation. Finally, the authors describe some of the potential future roles of PRP in clinical settings based on recent literature. These include Achilles tendon rupture, chronic tendinosis, chronic rotator cuff tendinopathy or tearing, muscle injury, and meniscal repair. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Empirical evaluation of the inter-relationship of articular elements involved in the pathoanatomy of knee osteoarthritis using magnetic resonance imaging.

PubMed

Meredith, Dennis S; Losina, Elena; Neumann, Gesa; Yoshioka, Hiroshi; Lang, Philipp K; Katz, Jeffrey N

2009-10-29

In this cross-sectional study, we conducted a comprehensive assessment of all articular elements that could be measured using knee MRI. We assessed the association of pathological change in multiple articular structures involved in the pathoanatomy of osteoarthritis. Knee MRI scans from patients over 45 years old were assessed using a semi-quantitative knee MRI assessment form. The form included six distinct elements: cartilage, bone marrow lesions, osteophytes, subchondral sclerosis, joint effusion and synovitis. Each type of pathology was graded using an ordinal scale with a value of zero indicating no pathology and higher values indicating increasingly severe levels of pathology. The principal dependent variable for comparison was the mean cartilage disease score (CDS), which captured the aggregate extent of involvement of articular cartilage. The distribution of CDS was compared to the individual and cumulative distributions of each articular element using the Chi-squared test. The correlations between pathological change in the various articular structures were assessed in a Spearman correlation table. Data from 140 patients were available for review. The cohort had a median age of 61 years (range 45-89) and was 61% female. The cohort included a wide spectrum of OA severity. Our analysis showed a statistically significant trend towards pathological change involving more articular elements as CDS worsened (p-value for trend < 0.0001). Comparison of CDS to change in the severity of pathology of individual articular elements showed statistically significant trends towards more severe pathology as CDS worsened for osteophytes (p-value for trend < 0.0001), bone marrow lesions (p = 0.0003), and subchondral sclerosis (p = 0.009), but not joint effusion or synovitis. There was a moderate correlation between cartilage damage, osteophytes and BMLs as well as a moderate correlation between joint effusion and synovitis. However, cartilage damage and osteophytes were only weakly associated with synovitis or joint effusion. Our results support an inter-relationship of multiple articular elements in the pathoanatomy of knee OA. Prospective studies of OA pathogenesis in humans are needed to correlate these findings to clinically relevant outcomes such as pain and function.

Proteomic Analysis of Connexin 43 Reveals Novel Interactors Related to Osteoarthritis*

PubMed Central

Gago-Fuentes, Raquel; Fernández-Puente, Patricia; Megias, Diego; Carpintero-Fernández, Paula; Mateos, Jesus; Acea, Benigno; Fonseca, Eduardo; Blanco, Francisco Javier; Mayan, Maria Dolores

2015-01-01

We have previously reported that articular chondrocytes in tissue contain long cytoplasmic arms that physically connect two distant cells. Cell-to-cell communication occurs through connexin channels termed Gap Junction (GJ) channels, which achieve direct cellular communication by allowing the intercellular exchange of ions, small RNAs, nutrients, and second messengers. The Cx43 protein is overexpressed in several human diseases and inflammation processes and in articular cartilage from patients with osteoarthritis (OA). An increase in the level of Cx43 is known to alter gene expression, cell signaling, growth, and cell proliferation. The interaction of proteins with the C-terminal tail of connexin 43 (Cx43) directly modulates GJ-dependent and -independent functions. Here, we describe the isolation of Cx43 complexes using mild extraction conditions and immunoaffinity purification. Cx43 complexes were extracted from human primary articular chondrocytes isolated from healthy donors and patients with OA. The proteomic content of the native complexes was determined using LC-MS/MS, and protein associations with Cx43 were validated using Western blot and immunolocalization experiments. We identified >100 Cx43-associated proteins including previously uncharacterized proteins related to nucleolar functions, RNA transport, and translation. We also identified several proteins involved in human diseases, cartilage structure, and OA as novel functional Cx43 interactors, which emphasized the importance of Cx43 in the normal physiology and structural and functional integrity of chondrocytes and articular cartilage. Gene Ontology (GO) terms of the proteins identified in the OA samples showed an enrichment of Cx43-interactors related to cell adhesion, calmodulin binding, the nucleolus, and the cytoskeleton in OA samples compared with healthy samples. However, the mitochondrial proteins SOD2 and ATP5J2 were identified only in samples from healthy donors. The identification of Cx43 interactors will provide clues to the functions of Cx43 in human cells and its roles in the development of several diseases, including OA. PMID:25903580

Targeting pro-inflammatory cytokines following joint injury: acute intra-articular inhibition of interleukin-1 following knee injury prevents post-traumatic arthritis

PubMed Central

2014-01-01

Introduction Post-traumatic arthritis (PTA) is a progressive, degenerative response to joint injury, such as articular fracture. The pro-inflammatory cytokines, interleukin 1(IL-1) and tumor necrosis factor alpha (TNF-α), are acutely elevated following joint injury and remain elevated for prolonged periods post-injury. To investigate the role of local and systemic inflammation in the development of post-traumatic arthritis, we targeted both the initial acute local inflammatory response and a prolonged 4 week systemic inflammatory response by inhibiting IL-1 or TNF-α following articular fracture in the mouse knee. Methods Anti-cytokine agents, IL-1 receptor antagonist (IL-1Ra) or soluble TNF receptor II (sTNFRII), were administered either locally via an acute intra-articular injection or systemically for a prolonged 4 week period following articular fracture of the knee in C57BL/6 mice. The severity of arthritis was then assessed at 8 weeks post-injury in joint tissues via histology and micro computed tomography, and systemic and local biomarkers were assessed in serum and synovial fluid. Results Intra-articular inhibition of IL-1 significantly reduced cartilage degeneration, synovial inflammation, and did not alter bone morphology following articular fracture. However, systemic inhibition of IL-1, and local or systemic inhibition of TNF provided no benefit or conversely led to increased arthritic changes in the joint tissues. Conclusion These results show that intra-articular IL-1, rather than TNF-α, plays a critical role in the acute inflammatory phase of joint injury and can be inhibited locally to reduce post-traumatic arthritis following a closed articular fracture. Targeted local inhibition of IL-1 following joint injury may represent a novel treatment option for PTA. PMID:24964765

Basic science and surgical treatment options for articular cartilage injuries of the knee.

PubMed

Tetteh, Elizabeth S; Bajaj, Sarvottam; Ghodadra, Neil S

2012-03-01

The complex structure of articular cartilage allows for diverse knee function throughout range of motion and weight bearing. However, disruption to the structural integrity of the articular surface can cause significant morbidity. Due to an inherently poor regenerative capacity, articular cartilage defects present a treatment challenge for physicians and therapists. For many patients, a trial of nonsurgical treatment options is paramount prior to surgical intervention. In instances of failed conservative treatment, patients can undergo an array of palliative, restorative, or reparative surgical procedures to treat these lesions. Palliative methods include debridement and lavage, while restorative techniques include marrow stimulation. For larger lesions involving subchondral bone, reparative procedures such as osteochondral grafting or autologous chondrocyte implantation are considered. Clinical success not only depends on the surgical techniques but also requires strict adherence to rehabilitation guidelines. The purpose of this article is to review the basic science of articular cartilage and to provide an overview of the procedures currently performed at our institution for patients presenting with symptomatic cartilage lesions.

Dynamic compressive properties of bovine knee layered tissue

NASA Astrophysics Data System (ADS)

Nishida, Masahiro; Hino, Yuki; Todo, Mitsugu

2015-09-01

In Japan, the most common articular disease is knee osteoarthritis. Among many treatment methodologies, tissue engineering and regenerative medicine have recently received a lot of attention. In this field, cells and scaffolds are important, both ex vivo and in vivo. From the viewpoint of effective treatment, in addition to histological features, the compatibility of mechanical properties is also important. In this study, the dynamic and static compressive properties of bovine articular cartilage-cancellous bone layered tissue were measured using a universal testing machine and a split Hopkinson pressure bar method. The compressive behaviors of bovine articular cartilage-cancellous bone layered tissue were examined. The effects of strain rate on the maximum stress and the slope of stress-strain curves of the bovine articular cartilage-cancellous bone layered tissue were discussed.

Transtendon, Double-Row, Transosseous-Equivalent Arthroscopic Repair of Partial-Thickness, Articular-Surface Rotator Cuff Tears

PubMed Central

Dilisio, Matthew F.; Miller, Lindsay R.; Higgins, Laurence D.

2014-01-01

Arthroscopic transtendinous techniques for the arthroscopic repair of partial-thickness, articular-surface rotator cuff tears offer the advantage of minimizing the disruption of the patient's remaining rotator cuff tendon fibers. In addition, double-row fixation of full-thickness rotator cuff tears has shown biomechanical advantages. We present a novel method combining these 2 techniques for transtendon, double-row, transosseous-equivalent arthroscopic repair of partial-thickness, articular-surface rotator cuff tears. Direct visualization of the reduction of the retracted articular tendon layer to its insertion on the greater tuberosity is the key to the procedure. Linking the medial-row anchors and using a double-row construct provide a stable repair that allows early shoulder motion to minimize the risk of postoperative stiffness. PMID:25473606

Transtendon, double-row, transosseous-equivalent arthroscopic repair of partial-thickness, articular-surface rotator cuff tears.

PubMed

Dilisio, Matthew F; Miller, Lindsay R; Higgins, Laurence D

2014-10-01

Arthroscopic transtendinous techniques for the arthroscopic repair of partial-thickness, articular-surface rotator cuff tears offer the advantage of minimizing the disruption of the patient's remaining rotator cuff tendon fibers. In addition, double-row fixation of full-thickness rotator cuff tears has shown biomechanical advantages. We present a novel method combining these 2 techniques for transtendon, double-row, transosseous-equivalent arthroscopic repair of partial-thickness, articular-surface rotator cuff tears. Direct visualization of the reduction of the retracted articular tendon layer to its insertion on the greater tuberosity is the key to the procedure. Linking the medial-row anchors and using a double-row construct provide a stable repair that allows early shoulder motion to minimize the risk of postoperative stiffness.

Investigation the efficacy of intra-articular prolotherapy with erythropoietin and dextrose and intra-articular pulsed radiofrequency on pain level reduction and range of motion improvement in primary osteoarthritis of knee

PubMed Central

Rahimzadeh, Poupak; Imani, Farnad; Faiz, Seyed Hamid Reza; Entezary, Saeed Reza; Nasiri, Ali Akbar; Ziaeefard, Mohsen

2014-01-01

Background: Osteoarthritis is one of the most common diseases and the knee is the most commonly affected joint. Intra-articular prolotherapy is being utilized in acute and chronic pain management setting. This study was designed to compare the efficacy of three methods of intra-articular knee joint therapies with erythropoietin, dextrose, and pulsed radiofrequency. Materials and Methods: After approval by the Ethics Committee and explaining the therapeutic method to volunteers, 70 patients who were suffering from primary knee osteoarthrosis went through one of the treatment methods (erythropoietin, dextrose, and pulsed radiofrequency). The study was double-blind randomized clinical trial performed from December 2012 to July 2013. Patients’ pain level was assessed through the visual analog pain scale (VAS), and range of motion (ROM) was measured by goniometric method. Furthermore, patients’ satisfaction was assessed before and after different treatment methods in weeks 2, 4, and 12. For analysis, Chi-square, one-way ANOVA, and repeated measured ANOVA were utilized. Results: The demographic results among the three groups did not indicate any statistical difference. The mean VAS in erythropoietin group in the 2nd, 4th, and 12th weeks was 3.15 ± 1.08, 3.15 ± 1.08, and 3.5 ± 1.23, respectively (P ≤ 0.005). Knee joint ROM in the erythropoietin group in the 2nd, 4th, and 12th weeks was 124 ± 1.50, 124 ± 1.4, and 123 ± 1.53 respectively (P ≤ 0.005). Satisfaction score in the 12th week in erythropoietin group was extremely satisfied 15%, satisfied 55%, and moderately satisfied 30%, (P = 0.005). No specific side-effects were observed. Conclusion: Intra-articular prolotherapy with erythropoietin was more effective in terms of pain level reduction and ROM improvement compared with dextrose and pulsed radiofrequency. PMID:25422652

Multiparametric MRI Assessment of Human Articular Cartilage Degeneration: Correlation with Quantitative Histology and Mechanical Properties

PubMed Central

Rautiainen, Jari; Nissi, Mikko J.; Salo, Elli-Noora; Tiitu, Virpi; Finnilä, Mikko A.J.; Aho, Olli-Matti; Saarakkala, Simo; Lehenkari, Petri; Ellermann, Jutta; Nieminen, Miika T.

2014-01-01

Purpose To evaluate the sensitivity of quantitative MRI techniques (T1, T1,Gd, T2, continous wave (CW) T1ρ dispersion, adiabatic T1ρ, adiabatic T2ρ, RAFF and inversion-prepared magnetization transfer (MT)) for assessment of human articular cartilage with varying degrees of natural degeneration. Methods Osteochondral samples (n = 14) were obtained from the tibial plateaus of patients undergoing total knee replacement. MRI of the specimens was performed at 9.4 T and the relaxation time maps were evaluated in the cartilage zones. For reference, quantitative histology, OARSI grading and biomechanical measurements were performed and correlated with MRI findings. Results All MRI parameters, except T1,Gd, showed statistically significant differences in tangential and full-thickness ROIs between early and advanced osteoarthritis (OA) groups, as classified by OARSI grading. CW-T1ρ showed significant dispersion in all ROIs and featured classical laminar structure of cartilage with spin-lock powers below 1000 Hz. Adiabatic T1ρ, T2ρ, CW-T1ρ, MT and RAFF correlated strongly with OARSI grade and biomechanical parameters. Conclusion MRI parameters were able to differentiate between early and advanced OA. Furthermore, rotating frame methods, namely adiabatic T1ρ, adiabatic T2ρ, CW-T1ρ and RAFF, as well as MT experiment correlated strongly with biomechanical parameters and OARSI grade, suggesting high sensitivity of the parameters for cartilage degeneration. PMID:25104181

Relationship between magnitude of applied torque in pre-swing phase and gait change for prevention of trip in elderly people.

PubMed

Miyake, Tamon; Tsukune, Mariko; Kobayashi, Yo; Sugano, Shigeki; Fujie, Masakatsu G

2016-08-01

Elderly people are at risk of tripping because of their narrow range of articular motion. To avoid tripping, gait training that improves their range of articular motion would be beneficial. In this study we propose a gait-training robot that applies a torque during the pre-swing phase to achieve this goal. We investigated the relationship between magnitude of applied torque and change in the range of knee-articular motion while walking before and after the application of this torque. We developed a wearable robot and carried out an experiment on human participants in which a motor pulls a string embedded on the robotic frame, applying torque in the pre-swing phase for a period of 20 [s]. Before and after applying torque the participant walked normally for 15 [s] without interference from the robot. We found that knee flexion angle increased after applying the torque if the torque was within the range of approximately 6-8 [Nm]. Therefore, we were able to verify that a new range of knee articular motion can be learned through application of torque.

Reference genes for normalization of gene expression studies in human osteoarthritic articular cartilage.

PubMed

Pombo-Suarez, Manuel; Calaza, Manuel; Gomez-Reino, Juan J; Gonzalez, Antonio

2008-01-29

Assessment of gene expression is an important component of osteoarthritis (OA) research, greatly improved by the development of quantitative real-time PCR (qPCR). This technique requires normalization for precise results, yet no suitable reference genes have been identified in human articular cartilage. We have examined ten well-known reference genes to determine the most adequate for this application. Analyses of expression stability in cartilage from 10 patients with hip OA, 8 patients with knee OA and 10 controls without OA were done with classical statistical tests and the software programs geNorm and NormFinder. Results from the three methods of analysis were broadly concordant. Some of the commonly used reference genes, GAPDH, ACTB and 18S RNA, performed poorly in our analysis. In contrast, the rarely used TBP, RPL13A and B2M genes were the best. It was necessary to use together several of these three genes to obtain the best results. The specific combination depended, to some extent, on the type of samples being compared. Our results provide a satisfactory set of previously unused reference genes for qPCR in hip and knee OA This confirms the need to evaluate the suitability of reference genes in every tissue and experimental situation before starting the quantitative assessment of gene expression by qPCR.

Synoviocyte Derived-Extracellular Matrix Enhances Human Articular Chondrocyte Proliferation and Maintains Re-Differentiation Capacity at Both Low and Atmospheric Oxygen Tensions

PubMed Central

Kean, Thomas J.; Dennis, James E.

2015-01-01

Background Current tissue engineering methods are insufficient for total joint resurfacing, and chondrocytes undergo de-differentiation when expanded on tissue culture plastic. De-differentiated chondrocytes show poor re-differentiation in culture, giving reduced glycosaminoglycan (GAG) and collagen matrix accumulation. To address this, porcine synoviocyte-derived extracellular matrix and low (5%) oxygen tension were assessed for their ability to enhance human articular chondrocyte expansion and maintain re-differentiation potential. Methods Porcine synoviocyte matrices were devitalized using 3 non-detergent methods. These devitalized synoviocyte matrices were compared against tissue culture plastic for their ability to support human chondrocyte expansion. Expansion was further compared at both low (5%), and atmospheric (20%) oxygen tension on all surfaces. Expanded cells then underwent chondrogenic re-differentiation in aggregate culture at both low and atmospheric oxygen tension. Aggregates were assessed for their GAG and collagen content both biochemically and histologically. Results Human chondrocytes expanded twice as fast on devitalized synoviocyte matrix vs. tissue culture plastic, and cells retained their re-differentiation capacity for twice the number of population doublings. There was no significant difference in growth rate between low and atmospheric oxygen tension. There was significantly less collagen type I, collagen type II, aggrecan and more MMP13 expression in cells expanded on synoviocyte matrix vs. tissue culture plastic. There were also significant effects due to oxygen tension on gene expression, wherein there was greater collagen type I, collagen type II, SOX9 and less MMP13 expression on tissue culture plastic compared to synoviocyte matrix. There was a significant increase in GAG, but not collagen, accumulation in chondrocyte aggregates re-differentiated at low oxygen tension over that achieved in atmospheric oxygen conditions. Conclusions Synoviocyte-derived matrix supports enhanced expansion of human chondrocytes such that the chondrocytes are maintained in a state from which they can re-differentiate into a cartilage phenotype after significantly more population doublings. Also, low oxygen tension supports GAG, but not collagen, accumulation. These findings are a step towards the production of a more functional, tissue engineered cartilage. PMID:26075742

Metrology to quantify wear and creep of polyethylene tibial knee inserts.

PubMed

Muratoglu, Orhun K; Perinchief, Rebecca S; Bragdon, Charles R; O'Connor, Daniel O; Konrad, Reto; Harris, William H

2003-05-01

Assessment of damage on articular surfaces of ultrahigh molecular weight polyethylene tibial knee inserts primarily has been limited to qualitative methods, such as visual observation and classification of features such as pitting, delamination, and subsurface cracking. Semiquantitative methods also have been proposed to determine the linear penetration and volume of the scar that forms on articular surfaces of tibial knee inserts. The current authors report a new metrologic method that uses a coordinate measuring machine to quantify the dimensions of this scar. The articular surface of the insert is digitized with the coordinate measuring machine before and after regular intervals of testing on a knee simulator. The volume and linear penetration of the scar are calculated by mathematically taking the difference between the digitized surface maps of the worn and unworn articular surfaces. Three conventional polyethylene tibial knee inserts of a posterior cruciate-sparing design were subjected to five million cycles of normal gait on a displacement-driven knee wear simulator in bovine serum. A metrologic method was used to calculate creep and wear contributions to the scar formation on each tibial plateau. Weight loss of the inserts was determined gravimetrically with the appropriate correction for fluid absorption. The total average wear volume was 43 +/- 9 and 41 +/- 4 mm3 measured by the metrologic and gravimetric methods, respectively. The wear rate averaged 8.3 +/- 0.9 and 8.5 +/- 1.6 mm3 per million cycles measured by the metrologic and gravimetric methods, respectively. These comparisons reflected strong agreement between the metrologic and gravimetric methods.

Cartilage defect repair in horses: Current strategies and recent developments in regenerative medicine of the equine joint with emphasis on the surgical approach.

PubMed

Cokelaere, Stefan; Malda, Jos; van Weeren, René

2016-08-01

Chondral and osteochondral lesions due to injury or other pathology are highly prevalent conditions in horses (and humans) and commonly result in the development of osteoarthritis and progression of joint deterioration. Regenerative medicine of articular cartilage is an emerging clinical treatment option for patients with articular cartilage injury or disease. Functional articular cartilage restoration, however, remains a major challenge, but the field is progressing rapidly and there is an increasing body of supportive clinical and scientific evidence. This review gives an overview of the established and emerging surgical techniques employed for cartilage repair in horses. Through a growing insight in surgical cartilage repair possibilities, surgeons might be more stimulated to explore novel techniques in a clinical setting. Copyright © 2016 Elsevier Ltd. All rights reserved.

Laser biostimulation of articular cartilage: in vitro evaluation

NASA Astrophysics Data System (ADS)

Jia, Yali; Guo, Zhouyi; Yang, Xiaohong; Zeng, Chang-Chun

2004-07-01

In the orthopaedic field, the repair of ariticular cartilage is still a difficult problem, because of the physiological characters of cartilaginous tissues and chondrocytes. To find an effective method of stimulating their regeneration, this in vitro study focuses on the biostimulation of rabbit articular chondrocytes by low-power He-Ne laser. The articular chondrocytes isolated from the cartilage of the medial condyle of the femur of the rabbit were incubated in HamF12 medium. The second passage culture were spread on 24 petri dishes and were irradiated with laser at power density of 2 - 12 mW/cm2 for 6.5 minutes, corresponding to the energy density of 1-6 J/cm2. Laser treatment was performed three times at a 24-hour interval. After lasering, incubation was continued for 24 hours. Non-irradiated cells were kept under the same conditions as the irradiated ones. The cell proliferation activity was evaluated with a XTT colorimetric method. Irradiation of 4 - 6 J/cm2 revealed a considerably higher cell proliferation activity comparing to control cultures. Thereinto, the energy density of 4 and 5 J/cm2 remarkably increased cell growth (P<0.01). The present study showed that a particular laser irradiation stimulates articular chondrocytes proliferation. These findings might be clinically relevant, indicating that low-power laser irradiation treatment is likely to achieve the repair of articular cartilage in clinic.

Transplantation of free tibial periosteal grafts for the repair of articular cartilage defect: An experimental study

PubMed Central

Singh, Ravijot; Chauhan, Vijendra; Chauhan, Neena; Sharma, Sansar

2009-01-01

Background: Articular chondrocytes have got a long lifespan but rarely divides after maturity. Thus, an articular cartilage has a limited capacity for repair. Periosteal grafts have chondrogenic potential and have been used to repair defects in the articular cartilage. The purpose of the present study is to investigate the differentiation of free periosteal grafts in the patellofemoral joint where the cambium layer faces the subchondral bone and to investigate the applicability of periosteal grafts in the reconstruction of articular surfaces. Materials and Methods: The study was carried out over a period of 1 year on 25 adult, male Indian rabbits after obtaining permission from the institutional animal ethical committee. A full-thickness osteochondral defect was created by shaving off the whole articular cartilage of the patella of the left knee. The defect thus created was grafted with free periosteal graft. The patella of the right knee was taken as a control where no grafting was done after shaving off the articular cartilage. The first animal was used to study the normal histology of the patellar articular cartilage and periosteum obtained from the medial surface of tibial condyle. Rest 24 animals were subjected to patellectomy, 4 each at serial intervals of 2, 4, 8, 16, 32 and 48 weeks and the patellar articular surfaces were examined macroscopically and histologically. Results: The grafts got adherent to the underlying patellar articular surface at the end of 4 weeks. Microscopically, graft incorporation could be appreciated at 4 weeks. Mesenchymal cells of the cambium layer were seen differentiating into chondrocytes by the end of 4 weeks in four grafts (100%) and they were arranged in a haphazard manner. Till the end of 8 weeks, the cellular arrangement was mostly wooly. At 16 weeks, one graft (25%) had wooly arrangement of chondrocytes and three grafts (75%) had columnar formation of cells. Same percentage was maintained at 32 weeks. Four grafts (100%) at 48 weeks showed columnar orientation. The control side showed no changes over the shaved off articular surface in all the rabbits. One rabbit at 4 weeks had a dislocation of the patella on the control side. None of the rabbits developed any infection or wound dehiscence. Conclusion: Autologous periosteal graft transplantation can be a promising substitute for articular cartilaginous defects. PMID:19838382

Hyaline cartilage formation and tumorigenesis of implanted tissues derived from human induced pluripotent stem cells.

PubMed

Saito, Taku; Yano, Fumiko; Mori, Daisuke; Kawata, Manabu; Hoshi, Kazuto; Takato, Tsuyoshi; Masaki, Hideki; Otsu, Makoto; Eto, Koji; Nakauchi, Hiromitsu; Chung, Ung-il; Tanaka, Sakae

2015-01-01

Induced pluripotent stem cells (iPSCs) are a promising cell source for cartilage regenerative medicine. Meanwhile, the risk of tumorigenesis should be considered in the clinical application of human iPSCs (hiPSCs). Here, we report in vitro chondrogenic differentiation of hiPSCs and maturation of the differentiated hiPSCs through transplantation into mouse knee joints. Three hiPSC clones showed efficient chondrogenic differentiation using an established protocol for human embryonic stem cells. The differentiated hiPSCs formed hyaline cartilage tissues at 8 weeks after transplantation into the articular cartilage of NOD/SCID mouse knee joints. Although tumors were not observed during the 8 weeks after transplantation, an immature teratoma had developed in one mouse at 16 weeks. In conclusion, hiPSCs are a potent cell source for regeneration of hyaline articular cartilage. However, the risk of tumorigenesis should be managed for clinical application in the future.

History of osteochondral allograft transplantation.

PubMed

Nikolaou, V S; Giannoudis, P V

2017-07-01

Osteochondral defects or injuries represent the most challenging entities to treat, especially when occur to young and active patients. For centuries, it has been recognized that such defects are almost impossible to treat. However, surgeons have never stopped the effort to develop reliable methods to restore articular cartilage and salvage the endangered joint function. Osteochondral allograft transplantation in human was first introduced by Eric Lexer in 1908. Since that era, several pioneers have been worked in the field of osteochondral allotransplantation, presenting and developing the basic research, the methodology and the surgical techniques. Herein we present in brief, the history and the early clinical results of osteochondral allograft transplantation in human. Copyright © 2017 Elsevier Ltd. All rights reserved.

A 3D quantitative comparison of trapezium and trapezoid relative articular and nonarticular surface areas in modern humans and great apes.

PubMed

Tocheri, M W; Razdan, A; Williams, R C; Marzke, M W

2005-11-01

The structure and functions of the modern human hand are critical components of what distinguishes Homo sapiens from the great apes (Gorilla, Pan, and Pongo). In this study, attention is focused on the trapezium and trapezoid, the two most lateral bones of the distal carpal row, in the four extant hominid genera, representing the first time they have been quantified and analyzed together as a morphological-functional complex. Our objective is to quantify the relative articular and nonarticular surface areas of these two bones and to test whether modern humans exhibit significant shape differences from the great apes, as predicted by previous qualitative analyses and the functional demands of differing manipulative and locomotor strategies. Modern humans were predicted to show larger relative first metacarpal and scaphoid surfaces on the trapezium because of the regular recruitment of the thumb during manipulative behaviors; alternatively, great apes were predicted to show larger relative second metacarpal and scaphoid surfaces on the trapezoid because of the functional demands on the hands during locomotor behaviors. Modern humans were also expected to exhibit larger relative mutual joint surfaces between the trapezoid and adjacent carpals than do the great apes because of assumed transverse loads generated by the functional demands of the modern human power grip. Using 3D bone models acquired through laser digitizing, the relative articular and nonarticular areas on each bone are quantified and compared. Multivariate analyses of these data clearly distinguish modern humans from the great apes. In total, the observed differences between modern humans and the great apes support morphological predictions based on the fact that this region of the human wrist is no longer involved in weight-bearing during locomotor behavior and is instead recruited solely for manipulative behaviors. The results provide the beginnings of a 3D comparative standard against which further extant and fossil primate wrist bones can be compared within the contexts of manipulative and locomotor behaviors.

Validity of histopathological grading of articular cartilage from osteoarthritic knee joints

PubMed Central

Ostergaard, K.; Andersen, C.; Petersen, J.; Bendtzen, K.; Salter, D.

1999-01-01

OBJECTIVES—To determine the validity of the histological-histochemical grading system (HHGS) for osteoarthritic (OA) articular cartilage.
METHODS—Human articular cartilage was obtained from macroscopically normal (n = 13) and OA (n = 21) knee joints. Sections of central and peripheral regions of normal samples were produced. Sections of regions containing severe, moderate, and mild OA changes were produced from each OA sample. A total of 89 sections were graded by means of the HHGS (0-14) twice by three observers.
RESULTS—Average scores for regions designated severe (8.64) and moderate (5.83) OA were less than the expected (10-14 and 6-9, respectively) according to the HHGS, whereas average scores for the region designated mild (5.29) OA and central and peripheral regions (2.19) of normal cartilage were higher than expected (2-5 and 0-1, respectively). The HHGS was capable of differentiating between articular cartilage from macroscopically normal and OA joints and between the region designated severe OA and other regions. However, the HHGS did not adequately differentiate between regions designated mild and moderate OA. Values for sensitivity, specificity, and efficiency for all regions varied considerably.
CONCLUSION—The HHGS is valid for normal and severe OA cartilage, but does not permit distinction between mild and moderate OA changes in articular cartilage.

 Keywords: histopathology; osteoarthritis; reliability; validity PMID:10364898

Engineering Lubrication in Articular Cartilage

PubMed Central

McNary, Sean M.; Athanasiou, Kyriacos A.

2012-01-01

Despite continuous progress toward tissue engineering of functional articular cartilage, significant challenges still remain. Advances in morphogens, stem cells, and scaffolds have resulted in enhancement of the bulk mechanical properties of engineered constructs, but little attention has been paid to the surface mechanical properties. In the near future, engineered tissues will be able to withstand and support the physiological compressive and tensile forces in weight-bearing synovial joints such as the knee. However, there is an increasing realization that these tissue-engineered cartilage constructs will fail without the optimal frictional and wear properties present in native articular cartilage. These characteristics are critical to smooth, pain-free joint articulation and a long-lasting, durable cartilage surface. To achieve optimal tribological properties, engineered cartilage therapies will need to incorporate approaches and methods for functional lubrication. Steady progress in cartilage lubrication in native tissues has pushed the pendulum and warranted a shift in the articular cartilage tissue-engineering paradigm. Engineered tissues should be designed and developed to possess both tribological and mechanical properties mirroring natural cartilage. In this article, an overview of the biology and engineering of articular cartilage structure and cartilage lubrication will be presented. Salient progress in lubrication treatments such as tribosupplementation, pharmacological, and cell-based therapies will be covered. Finally, frictional assays such as the pin-on-disk tribometer will be addressed. Knowledge related to the elements of cartilage lubrication has progressed and, thus, an opportune moment is provided to leverage these advances at a critical step in the development of mechanically and tribologically robust, biomimetic tissue-engineered cartilage. This article is intended to serve as the first stepping stone toward future studies in functional tissue engineering of articular cartilage that begins to explore and incorporate methods of lubrication. PMID:21955119

Intra-articular injection of a nutritive mixture solution protects articular cartilage from osteoarthritic progression induced by anterior cruciate ligament transection in mature rabbits: a randomized controlled trial

PubMed Central

Park, Yoo-Sin; Lim, Si-Woong; Lee, Il-Hoon; Lee, Tae-Jin; Kim, Jong-Sung; Han, Jin Soo

2007-01-01

Osteoarthritis (OA) is a degenerative disease that disrupts the collagenous matrix of articular cartilage and is difficult to cure because articular cartilage is a nonvascular tissue. Treatment of OA has targeted macromolecular substitutes for cartilage components, such as hyaluronic acid or genetically engineered materials. However, the goal of the present study was to examine whether intra-articular injection of the elementary nutrients restores the matrix of arthritic knee joints in mature animals. A nutritive mixture solution (NMS) was composed of elementary nutrients such as glucose or dextrose, amino acids and ascorbic acid. It was administered five times (at weeks 6, 8, 10, 13 and 16) into the unilateral anterior cruciate ligament transected knee joints of mature New Zealand White rabbits, and the effect of NMS injection was compared with that of normal saline. OA progression was histopathologically evaluated by haematoxylin and eosin staining, by the Mankin grading method and by scanning electron microscopy at week 19. NMS injection decreased progressive erosion of articular cartilage overall compared with injection of normal saline (P < 0.01), and nms joints exhibited no differences relative to normal cartilage that had not undergone transection of the anterior cruciate ligament, as assessed using the mankin grading method. Haematoxylin and eosin staining and scanning electron microscopy findings also indicated that nms injection, in constrast to normal saline injection, restored the cartilage matrix, which is known to be composed of a collagen and proteoglycan network. thus, nms injection is a potent treatment that significantly retards oa progression, which in turn prevents progressive destruction of joints and functional loss in mature animals. PMID:17257416

Endogenous versus Exogenous Growth Factor Regulation of Articular Chondrocytes

PubMed Central

Shi, Shuiliang; Chan, Albert G.; Mercer, Scott; Eckert, George J.; Trippel, Stephen B.

2014-01-01

Anabolic growth factors that regulate the function of articular chondrocytes are candidates for articular cartilage repair. Such factors may be delivered by pharmacotherapy in the form of exogenous proteins, or by gene therapy as endogenous proteins. It is unknown whether delivery method influences growth factor effectiveness in regulating articular chondrocyte reparative functions. We treated adult bovine articular chondrocytes with exogenous recombinant insulin-like growth factor-I (IGF-I) and transforming growth factor-beta1 (TGF-β1), or with the genes encoding these growth factors for endogenous production. Treatment effects were measured as change in chondrocyte DNA content, glycosaminoglycan production, and aggrecan gene expression. We found that IGF-I stimulated chondrocyte biosynthesis similarly when delivered by either exogenous or endogenous means. In contrast, exogenous TGF-ß1 stimulated these reparative functions, while endogenous TGF-ß1 had little effect. Endogenous TGF-ß1 became more bioactive following activation of the transgene protein product. These data indicate that effective mechanisms of growth factor delivery for articular cartilage repair may differ for different growth factors. In the case of IGF-I, gene therapy or protein therapy appear to be viable options. In contrast, TGF-ß1 gene therapy may be constrained by a limited ability of chondrocytes to convert latent complexes to an active form. PMID:24105960

Glucocorticoid resorption and influence on the hypothalamic‐pituitary‐adrenal axis after intra‐articular treatment of the knee in resting and mobile patients

PubMed Central

Weitoft, T; Rönnblom, L

2006-01-01

Background Studies have shown that intra‐articular glucocorticoid injection treatment for knee synovitis has a better outcome in resting patients than in mobile patients. One reason for this observation might be that rest retards steroid resorption, causing an enhanced local treatment effect. Objectives To study drug resorption and the impact on hormone production in the hypothalamic‐pituitary‐adrenal axis after intra‐articular glucocorticoid administration, with and without postinjection rest. Methods Twenty patients with rheumatoid arthritis and knee synovitis were randomised to either 24 hour bed rest or normal activity after intra‐articular glucocorticoid treatment with 20 mg triamcinolone hexacetonide (THA). Serum levels of THA, cortisol, and adrenocorticotropic hormone (ACTH) were followed during 2 weeks. Results Short term and reversible decreases in serum cortisol and ACTH levels (p<0.001) were seen, without any significant differences between resting and mobile patients. The THA levels increased similarly in both groups, with the median serum peak seen after 8 hours. Conclusion Immobilisation does not appear to retard glucocorticoid resorption after intra‐articular administration. Further studies are therefore needed to clarify the mechanism behind the beneficial effects of rest after intra‐articular glucocorticoid treatment for knee synovitis. PMID:16769782

Use magnetic resonance imaging to assess articular cartilage

PubMed Central

Wang, Yuanyuan; Wluka, Anita E.; Jones, Graeme; Ding, Changhai

2012-01-01

Magnetic resonance imaging (MRI) enables a noninvasive, three-dimensional assessment of the entire joint, simultaneously allowing the direct visualization of articular cartilage. Thus, MRI has become the imaging modality of choice in both clinical and research settings of musculoskeletal diseases, particular for osteoarthritis (OA). Although radiography, the current gold standard for the assessment of OA, has had recent significant technical advances, radiographic methods have significant limitations when used to measure disease progression. MRI allows accurate and reliable assessment of articular cartilage which is sensitive to change, providing the opportunity to better examine and understand preclinical and very subtle early abnormalities in articular cartilage, prior to the onset of radiographic disease. MRI enables quantitative (cartilage volume and thickness) and semiquantitative assessment of articular cartilage morphology, and quantitative assessment of cartilage matrix composition. Cartilage volume and defects have demonstrated adequate validity, accuracy, reliability and sensitivity to change. They are correlated to radiographic changes and clinical outcomes such as pain and joint replacement. Measures of cartilage matrix composition show promise as they seem to relate to cartilage morphology and symptoms. MRI-derived cartilage measurements provide a useful tool for exploring the effect of modifiable factors on articular cartilage prior to clinical disease and identifying the potential preventive strategies. MRI represents a useful approach to monitoring the natural history of OA and evaluating the effect of therapeutic agents. MRI assessment of articular cartilage has tremendous potential for large-scale epidemiological studies of OA progression, and for clinical trials of treatment response to disease-modifying OA drugs. PMID:22870497

Computational aspects in mechanical modeling of the articular cartilage tissue.

PubMed

Mohammadi, Hadi; Mequanint, Kibret; Herzog, Walter

2013-04-01

This review focuses on the modeling of articular cartilage (at the tissue level), chondrocyte mechanobiology (at the cell level) and a combination of both in a multiscale computation scheme. The primary objective is to evaluate the advantages and disadvantages of conventional models implemented to study the mechanics of the articular cartilage tissue and chondrocytes. From monophasic material models as the simplest form to more complicated multiscale theories, these approaches have been frequently used to model articular cartilage and have contributed significantly to modeling joint mechanics, addressing and resolving numerous issues regarding cartilage mechanics and function. It should be noted that attentiveness is important when using different modeling approaches, as the choice of the model limits the applications available. In this review, we discuss the conventional models applicable to some of the mechanical aspects of articular cartilage such as lubrication, swelling pressure and chondrocyte mechanics and address some of the issues associated with the current modeling approaches. We then suggest future pathways for a more realistic modeling strategy as applied for the simulation of the mechanics of the cartilage tissue using multiscale and parallelized finite element method.

Intra-articular temperatures of the knee in sports – An in-vivo study of jogging and alpine skiing

PubMed Central

Becher, Christoph; Springer, Jan; Feil, Sven; Cerulli, Guiliano; Paessler, Hans H

2008-01-01

Background Up to date, no information exists about the intra-articular temperature changes of the knee related to activity and ambient temperature. Methods In 6 healthy males, a probe for intra-articular measurement was inserted into the notch of the right knee. Each subject was jogging on a treadmill in a closed room at 19°C room temperature and skiing in a ski resort at -3°C outside temperature for 60 minutes. In both conditions, temperatures were measured every fifteen minutes intra-articulary and at the skin surface of the knee. A possible influence on joint function and laxity was evaluated before and after activity. Statistical analysis of intra-articular and skin temperatures was done using nonparametric Wilcoxon's sign rank sum test and Mann-Whitney's-U-Test. Results Median intra-articular temperatures increased from 31.4°C before activity by 2.1°C, 4°C, 5.8°C and 6.1°C after 15, 30, 45 and 60 min of jogging (all p ≤ 0.05). Median intra-articular temperatures dropped from 32.2°C before activity by 0.5°C, 1.9°C, 3.6°C and 1.1°C after 15, 30, 45 and 60 min of skiing (all n.s.). After 60 minutes of skiing (jogging), the median intra-articular temperature was 19.6% (8.7%) higher than the skin surface temperature at the knee. Joint function and laxity appeared not to be different before and after activity within both groups. Conclusion This study demonstrates different changes of intra-articular and skin temperatures during sports in jogging and alpine skiing and suggests that changes are related to activity and ambient temperature. PMID:18405365

Muscle-driven finite element simulation of human foot movements.

PubMed

Spyrou, L A; Aravas, N

2012-01-01

This paper describes a finite element scheme for realistic muscle-driven simulation of human foot movements. The scheme is used to simulate human ankle plantar flexion. A three-dimensional anatomically detailed finite element model of human foot and lower leg is developed and the idea of generating natural foot movement based entirely on the contraction of the plantar flexor muscles is used. The bones, ligaments, articular cartilage, muscles, tendons, as well as the rest soft tissues of human foot and lower leg are included in the model. A realistic three-dimensional continuum constitutive model that describes the biomechanical behaviour of muscles and tendons is used. Both the active and passive properties of muscle tissue are accounted for. The materials for bones and ligaments are considered as homogeneous, isotropic and linearly elastic, whereas the articular cartilage and the rest soft tissues (mainly fat) are defined as hyperelastic materials. The model is used to estimate muscle tissue deformations as well as stresses and strains that develop in the lower leg muscles during plantar flexion of the ankle. Stresses and strains that develop in Achilles tendon during such a movement are also investigated.

Annexin A6 interacts with p65 and stimulates NF-κB activity and catabolic events in articular chondrocytes.

PubMed

Campbell, Kirk A; Minashima, Takeshi; Zhang, Ying; Hadley, Scott; Lee, You Jin; Giovinazzo, Joseph; Quirno, Martin; Kirsch, Thorsten

2013-12-01

ANXA6, the gene for annexin A6, is highly expressed in osteoarthritic (OA) articular chondrocytes but not in healthy articular chondrocytes. This study was undertaken to determine whether annexin A6 affects catabolic events in these cells. Articular chondrocytes were isolated from Anxa6-knockout mice, wild-type (WT) mice, and human articular cartilage in which ANXA6 was overexpressed. Cells were treated with interleukin-1β (IL-1β) or tumor necrosis factor α (TNFα), and expression of catabolic genes and activation of NF-κB were determined by real-time polymerase chain reaction and luciferase reporter assay. Anxa6(-/-) and WT mouse knee joints were injected with IL-1β or the medial collateral ligament was transected and partial resection of the medial meniscus was performed to determine the role of Anxa6 in IL-1β-mediated cartilage destruction and OA progression. The mechanism by which Anxa6 stimulates NF-κB activity was determined by coimmunoprecipitation and immunoblot analysis of nuclear and cytoplasmic fractions of IL-1β-treated Anxa6(-/-) and WT mouse chondrocytes for p65 and Anxa6. Loss of Anxa6 resulted in decreased NF-κB activation and catabolic marker messenger RNA (mRNA) levels in IL-1β- or TNFα-treated articular chondrocytes, whereas overexpression of ANXA6 resulted in increased NF-κB activity and catabolic marker mRNA levels. Annexin A6 interacted with p65, and loss of Anxa6 caused decreased nuclear translocation and retention of the active p50/p65 NF-κB complex. Cartilage destruction in Anxa6(-/-) mouse knee joints after IL-1β injection or partial medial meniscectomy was reduced as compared to that in WT mouse joints. Our data define a role of annexin A6 in the modulation of NF-κB activity and in the stimulation of catabolic events in articular chondrocytes. Copyright © 2013 by the American College of Rheumatology.

[Comparison of external fixation with or without limited internal fixation for open knee fractures].

PubMed

Li, K N; Lan, H; He, Z Y; Wang, X J; Yuan, J; Zhao, P; Mu, J S

2018-03-01

Objective: To explore the characteristics and methods of different fixation methods and prevention of open knee joint fracture. Methods: The data of 86 cases of open knee joint fracture admitted from January 2002 to December 2015 in Department of Orthopaedics, Affiliated Hospital of Chengdu University were analyzed retrospectively.There were 65 males and 21 females aged of 38.6 years. There were 38 cases treated with trans articular external fixation alone, 48 cases were in the trans articular external fixation plus auxiliary limited internal fixation group. All the patients were treated according to the same three stages except for different fixation methods. Observation of external fixation and fracture fixation, fracture healing, wound healing and treatment, treatment and related factors of infection control and knee function recovery. χ(2) test was used to analyze data. Results: Eleven patients had primary wound healing, accounting for 12.8%. Seventy-five patients had two wounds healed, accounting for 87.2%. Only 38 cases of trans articular external fixator group had 31 cases of articular surface reduction, accounting for 81.6%; Five cases of trans articular external fixator assisted limited internal fixation group had 5 cases of poor reduction, accounting for 10.4%; There was significant difference between the two groups (χ(2)=44.132, P <0.05). Take a single cross joint external fixation group, a total of 23 cases of patients with infection, accounted for 60.5% of external fixation group; trans articular external fixation assisted limited internal fixation group there were 30 cases of patients with infection, accounting for the assistance of external fixator and limited internal fixation group 62.5%; There was significant difference between the two groups(χ(2)=0.035, P >0.05). Five cases of fracture nonunion cases of serious infection, patients voluntarily underwent amputation. The Lysholm Knee Scale: In the external fixation group, 23 cases were less than 50 points, accounting for 60.5%, 15 cases were more than 50 points, accounting for 39.5%, external fixation and limited internal fixation group 20 cases were less than 50 points, accounting for 41.7%, 28 cases were more than 50 points, accounting for 58.3%; There was significant difference between the two groups(χ(2)=1.279, P >0.05). Conclusions: Prevention and control of infection is a central link in the treatment of open fracture of the knee. Trans articular external fixator plus limited internal fixation is an important measure to treat open fracture of the knee-joint.

3D Printing of Cytocompatible Water-Based Light-Cured Polyurethane with Hyaluronic Acid for Cartilage Tissue Engineering Applications

PubMed Central

Shie, Ming-You; Chang, Wen-Ching; Wei, Li-Ju; Huang, Yu-Hsin; Chen, Chien-Han; Shih, Cheng-Ting; Chen, Yi-Wen; Shen, Yu-Fang

2017-01-01

Diseases in articular cartilages have affected millions of people globally. Although the biochemical and cellular composition of articular cartilages is relatively simple, there is a limitation in the self-repair ability of the cartilage. Therefore, developing strategies for cartilage repair is very important. Here, we report on a new liquid resin preparation process of water-based polyurethane based photosensitive materials with hyaluronic acid with application of the materials for 3D printed customized cartilage scaffolds. The scaffold has high cytocompatibility and is one that closely mimics the mechanical properties of articular cartilages. It is suitable for culturing human Wharton’s jelly mesenchymal stem cells (hWJMSCs) and the cells in this case showed an excellent chondrogenic differentiation capacity. We consider that the 3D printing hybrid scaffolds may have potential in customized tissue engineering and also facilitate the development of cartilage tissue engineering. PMID:28772498

Diverse roles of integrin receptors in articular cartilage.

PubMed

Shakibaei, M; Csaki, C; Mobasheri, A

2008-01-01

Integrins are heterodimeric integral membrane proteins made up of alpha and beta subunits. At least eighteen alpha and eight beta subunit genes have been described in mammals. Integrin family members are plasma membrane receptors involved in cell adhesion and active as intra- and extracellular signalling molecules in a variety of processes including embryogenesis, hemostasis, tissue repair, immune response and metastatic spread of tumour cells. Integrin beta 1 (beta1-integrin), the protein encoded by the ITGB1 gene (also known as CD29 and VLAB), is a multi-functional protein involved in cell-matrix adhesion, cell signalling, cellular defense, cell adhesion, protein binding, protein heterodimerisation and receptor-mediated activity. It is highly expressed in the human body (17.4 times higher than the average gene in the last updated revision of the human genome). The extracellular matrix (ECM) of articular cartilage is a unique environment. Interactions between chondrocytes and the ECM regulate many biological processes important to homeostasis and repair of articular cartilage, including cell attachment, growth, differentiation and survival. The beta1-integrin family of cell surface receptors appears to play a major role in mediating cell-matrix interactions that are important in regulating these fundamental processes. Chondrocyte mechanoreceptors have been proposed to incorporate beta1-integrins and mechanosensitive ion channels which link with key ECM, cytoskeletal and signalling proteins to maintain the chondrocyte phenotype, prevent chondrocyte apoptosis and regulate chondrocyte-specific gene expression. This review focuses on the expression and function of beta1-integrins in articular chondrocytes, its role in the unique biology of these cells and its distribution in cartilage.

Factors affecting wound ooze in total knee replacement

PubMed Central

Butt, U; Ahmad, R; Aspros, D; Bannister, GC

2010-01-01

INTRODUCTION Wound ooze is common following total knee arthroplasty (TKA) and persistent wound infection is a risk factor for infection, and increased length and cost of hospitalisation. PATIENTS AND METHODS We undertook a prospective study to assess the effect of tourniquet time, peri-articular local anaesthesia and surgical approach on wound oozing after TKA. RESULTS The medial parapatellar approach was used in 59 patients (77%) and subvastus in 18 patients (23%). Peri-articular local anaesthesia (0.25% Bupivacaine with 1:1,000,000 adrenalin) was used in 34 patients (44%). The mean tourniquet time was 83 min (range, 38–125 min). We found a significant association between cessation of oozing and peri-articular local anaesthesia (P = 0.003), length of the tourniquet time (P = 0.03) and the subvastus approach (P = 0.01). CONCLUSIONS Peri-articular local anaesthesia, the subvastus approach and shorter tourniquet time were all associated with less wound oozing after total knee arthroplasty. PMID:20836920

Mesenchymal stem-cell potential in cartilage repair: an update

PubMed Central

Mazor, M; Lespessailles, E; Coursier, R; Daniellou, R; Best, T M; Toumi, H

2014-01-01

Articular cartilage damage and subsequent degeneration are a frequent occurrence in synovial joints. Treatment of these lesions is a challenge because this tissue is incapable of quality repair and/or regeneration to its native state. Non-operative treatments endeavour to control symptoms and include anti-inflammatory medications, viscosupplementation, bracing, orthotics and activity modification. Classical surgical techniques for articular cartilage lesions are frequently insufficient in restoring normal anatomy and function and in many cases, it has not been possible to achieve the desired results. Consequently, researchers and clinicians are focusing on alternative methods for cartilage preservation and repair. Recently, cell-based therapy has become a key focus of tissue engineering research to achieve functional replacement of articular cartilage. The present manuscript is a brief review of stem cells and their potential in the treatment of early OA (i.e. articular cartilage pathology) and recent progress in the field. PMID:25353372

Identification of Fibroblast Growth Factor-18 as a Molecule to Protect Adult Articular Cartilage by Gene Expression Profiling*

PubMed Central

Mori, Yoshifumi; Saito, Taku; Chang, Song Ho; Kobayashi, Hiroshi; Ladel, Christoph H.; Guehring, Hans; Chung, Ung-il; Kawaguchi, Hiroshi

2014-01-01

To identify genes that maintain the homeostasis of adult articular cartilage and regenerate its lesions, we initially compared four types of chondrocytes: articular (AA) versus growth plate (AG) cartilage chondrocytes in adult rats, and superficial layer (IS) versus deep layer (ID) chondrocytes of epiphyseal cartilage in infant rats. Microarray analyses revealed that 40 and 186 genes had ≥10-fold higher expression ratios of AA/AG and IS/ID, respectively, and 16 genes showed ≥10-fold of both AA/AG and IS/ID ratios. The results were validated by real-time RT-PCR analysis. Among them, Hoxd1, Fgf18, and Esm1 were expressed more strongly in AA than in IS. Fgf18 was the extracellular and secreted factor that decreased glycosaminoglycan release and depletion from the cartilage, and enhanced proliferation of articular chondrocytes. Fgf18 was strongly expressed in the articular cartilage chondrocytes of adult rats. In a surgical rat osteoarthritis model, a once-weekly injection of recombinant human FGF18 (rhFGF18) given 3 weeks after surgery prevented cartilage degeneration in a dose-dependent manner at 6 and 9 weeks after surgery, with significant effect at 10 μg/week of rhFGF18. As the underlying mechanism, rhFGF18 strongly up-regulated Timp1 expression in the cell and organ cultures, and inhibition of aggrecan release by rhFGF18 was restored by addition of an antibody to Timp1. In conclusion, we have identified Fgf18 as a molecule that protects articular cartilage by gene expression profiling, and the anticatabolic effects may at least partially be mediated by the Timp1 expression. PMID:24577103

Sustained intra-articular release of celecoxib in an equine repeated LPS synovitis model.

PubMed

Cokelaere, Stefan M; Plomp, Saskia G M; de Boef, Esther; de Leeuw, Mike; Bool, Sophie; van de Lest, Chris H A; René van Weeren, P; Korthagen, Nicoline M

2018-05-02

Synovial inflammation is an important characteristic of arthritic disorders like osteoarthritis and rheumatoid arthritis. Orally administered non-steroidal anti-inflammatory drugs (NSAIDs) such as celecoxib are among the most widely prescribed drugs to manage these debilitating diseases. Intra-articular delivery in biodegradable in situ forming hydrogels overcomes adverse systemic effects and prolongs drug retention in the joint. In this study two formulations of celecoxib (40 mg/g and 120 mg/g) in a propyl-capped PCLA-PEG-PCLA triblock copolymer were sequentially evaluated in a multiple LPS challenge equine synovitis model. Intra-articular release and systemic exposure to celecoxib and local changes at joint level were evaluated longitudinally. A single intra-articular injection of the high dose (HCLB)-gel or low dose (LCLB)-gel showed a sustained and controlled intra-articular release in both inflamed and healthy joints together with very low systemic exposure. Synovitis and lameness were moderate respectively very mild in this model due to the low concentration LPS (0.25 ng/joint). Both celecoxib formulations had a mild, transient effect on inflammatory and structural synovial fluid biomarkers but these returned to baseline within one week of administration. The HCLB-gel showed a significant inhibition in peak white blood cell concentration at 8 hours after LPS induction. Elevated levels of celecoxib were observed in the joint for up to 30 days but no overall anti-inflammatory effects could be observed, which was thought to be due to the moderate synovitis. As there were no long-term adverse effects, sustained intra-articular release of celecoxib from in situ forming hydrogels should be evaluated further for its effects on longer-term relief of inflammatory joint pain in humans and animals. Copyright © 2018. Published by Elsevier B.V.

Optimal 3D culture of primary articular chondrocytes for use in the rotating wall vessel bioreactor.

PubMed

Mellor, Liliana F; Baker, Travis L; Brown, Raquel J; Catlin, Lindsey W; Oxford, Julia Thom

2014-08-01

Reliable culturing methods for primary articular chondrocytes are essential to study the effects of loading and unloading on joint tissue at the cellular level. Due to the limited proliferation capacity of primary chondrocytes and their tendency to dedifferentiate in conventional culture conditions, long-term culturing conditions of primary chondrocytes can be challenging. The goal of this study was to develop a suspension culturing technique that not only would retain the cellular morphology, but also maintain the gene expression characteristics of primary articular chondrocytes. Three-dimensional culturing methods were compared and optimized for primary articular chondrocytes in the rotating wall vessel bioreactor, which changes the mechanical culture conditions to provide a form of suspension culture optimized for low shear and turbulence. We performed gene expression analysis and morphological characterization of cells cultured in alginate beads, Cytopore-2 microcarriers, primary monolayer culture, and passaged monolayer cultures using reverse transcription-PCR and laser scanning confocal microscopy. Primary chondrocytes grown on Cytopore-2 microcarriers maintained the phenotypical morphology and gene expression pattern observed in primary bovine articular chondrocytes, and retained these characteristics for up to 9 d. Our results provide a novel and alternative culturing technique for primary chondrocytes suitable for studies that require suspension such as those using the rotating wall vessel bioreactor. In addition, we provide an alternative culturing technique for primary chondrocytes that can impact future mechanistic studies of osteoarthritis progression, treatments for cartilage damage and repair, and cartilage tissue engineering.

Bonding of human meniscal and articular cartilage with photoactive 1,8-naphthalimide dyes

NASA Astrophysics Data System (ADS)

Judy, Millard M.; Nosir, Hany R.; Jackson, Robert W.; Matthews, James Lester; Lewis, David E.; Utecht, Ronald E.; Yuan, Dongwu

1996-05-01

This study focused on meniscal cartilage repair by using the laser-activated photoactive 1,8- naphthalimide dye N,N'-bis-{6-[2-(2-(2- aminoethoxy)ethoxy)ethoxyethyl]amino-1H-benz (de)isoquinolin-1,3(2H)-dion-2- yl}-1,11-diamino-3,6,9-trioxaundecane. Harvested cadaveric human menisci were debrided and carved into strips 1 mm thick, 10 mm long, and 3 mm wide. Each strip was divided into two flaps, the surface painted with photoactive dye, the painted surfaces overlapped, the sample wrapped in Saran film, and the composite sandwiched between two glass slides at a pressure of approximately 3 kg/cm2. The sample then was transilluminated by argon ion laser light of 457.9-nm wavelength at a power density of 200 mW/cm2 with exposure times up to 5 h (3902 J/cm2 energy density). Essentially, the same procedures were performed for human femoral articular cartilage samples. Control experiments were conducted with laser irradiation alone and with dye alone. All the specimens were stored in isotonic saline solution for 2 h after irradiation to ensure hydration. The bond shear-strength was then tested and samples prepared for optical and electron transmission microscopy. Shear strength values of up to 1.8 kg/cm2 for meniscal tissues and 1.2 kg/cm2 for articular cartilaginous tissues were obtained for exposures of 3902 J/cm2. Shear strength values of approximately 0.9 kg/cm2 and 0.4 kg/cm2, respectively, for meniscus and cartilage were obtained with 459 J/cm2 exposure. Dye- and light-only controls exhibited 0 kg/cm2 shear strength values. Microscopy revealed close contact at the bonded surface in the laser-activated, dye-treated-specimens. This study shows that the laser-activated photoactive dyes have the capability of athermally bonding the meniscal and articular cartilage surfaces.

IL-1beta, but not BMP-7 leads to a dramatic change in the gene expression pattern of human adult articular chondrocytes--portraying the gene expression pattern in two donors.

PubMed

Saas, J; Haag, J; Rueger, D; Chubinskaya, S; Sohler, F; Zimmer, R; Bartnik, E; Aigner, T

2006-10-01

Anabolic and catabolic cytokines and growth factors such as BMP-7 and IL-1beta play a central role in controlling the balance between degradation and repair of normal and (osteo)arthritic articular cartilage matrix. In this report, we investigated the response of articular chondrocytes to these factors IL-1beta and BMP-7 in terms of changes in gene expression levels. Large scale analysis was performed on primary human adult articular chondrocytes isolated from two human, independent donors cultured in alginate beads (non-stimulated and stimulated with IL-1beta and BMP-7 for 48 h) using Affymetrix gene chips (oligo-arrays). Biostatistical and bioinformatic evaluation of gene expression pattern was performed using the Resolver software (Rosetta). Part of the results were confirmed using real-time PCR. IL-1beta modulated significantly 909 out of 3459 genes detectable, whereas BMP-7 influenced only 36 out of 3440. BMP-7 induced mainly anabolic activation of chondrocytes including classical target genes such as collagen type II and aggrecan, while IL-1beta, both, significantly modulated the gene expression levels of numerous genes; namely, IL-1beta down-regulated the expression of anabolic genes and induced catabolic genes and mediators. Our data indicate that BMP-7 has only a limited effect on differentiated cells, whereas IL-1beta causes a dramatic change in gene expression pattern, i.e. induced or repressed much more genes. This presumably reflects the fact that BMP-7 signaling is effected via one pathway only (i.e. Smad-pathway) whereas IL-1beta is able to signal via a broad variety of intracellular signaling cascades involving the JNK, p38, NFkB and Erk pathways and even influencing BMP signaling.

Quantifying NMR relaxation correlation and exchange in articular cartilage with time domain analysis

NASA Astrophysics Data System (ADS)

Mailhiot, Sarah E.; Zong, Fangrong; Maneval, James E.; June, Ronald K.; Galvosas, Petrik; Seymour, Joseph D.

2018-02-01

Measured nuclear magnetic resonance (NMR) transverse relaxation data in articular cartilage has been shown to be multi-exponential and correlated to the health of the tissue. The observed relaxation rates are dependent on experimental parameters such as solvent, data acquisition methods, data analysis methods, and alignment to the magnetic field. In this study, we show that diffusive exchange occurs in porcine articular cartilage and impacts the observed relaxation rates in T1-T2 correlation experiments. By using time domain analysis of T2-T2 exchange spectroscopy, the diffusive exchange time can be quantified by measurements that use a single mixing time. Measured characteristic times for exchange are commensurate with T1 in this material and so impacts the observed T1 behavior. The approach used here allows for reliable quantification of NMR relaxation behavior in cartilage in the presence of diffusive fluid exchange between two environments.

* Human Amniotic Mesenchymal Stromal Cells as Favorable Source for Cartilage Repair.

PubMed

Muiños-López, Emma; Hermida-Gómez, Tamara; Fuentes-Boquete, Isaac; de Toro-Santos, Javier; Blanco, Francisco Javier; Díaz-Prado, Silvia María

2017-09-01

Localized trauma-derived breakdown of the hyaline articular cartilage may progress toward osteoarthritis, a degenerative condition characterized by total loss of articular cartilage and joint function. Tissue engineering technologies encompass several promising approaches with high therapeutic potential for the treatment of these focal defects. However, most of the research in tissue engineering is focused on potential materials and structural cues, while little attention is directed to the most appropriate source of cells endowing these materials. In this study, using human amniotic membrane (HAM) as scaffold, we defined a novel static in vitro model for cartilage repair. In combination with HAM, four different cell types, human chondrocytes, human bone marrow-derived mesenchymal stromal cells (hBMSCs), human amniotic epithelial cells, and human amniotic mesenchymal stromal cells (hAMSCs) were assessed determining their therapeutic potential. A chondral lesion was drilled in human cartilage biopsies simulating a focal defect. A pellet of different cell types was implanted inside the lesion and covered with HAM. The biopsies were maintained for 8 weeks in culture. Chondrogenic differentiation in the defect was analyzed by histology and immunohistochemistry. HAM scaffold showed good integration and adhesion to the native cartilage in all groups. Although all cell types showed the capacity of filling the focal defect, hBMSCs and hAMSCs demonstrated higher levels of new matrix synthesis. However, only the hAMSCs-containing group presented a significant cytoplasmic content of type II collagen when compared with chondrocytes. More collagen type I was identified in the new synthesized tissue of hBMSCs. In accordance, hBMSCs and hAMSCs showed better International Cartilage Research Society scoring although without statistical significance. HAM is a useful material for articular cartilage repair in vitro when used as scaffold. In combination with hAMSCs, HAM showed better potential for cartilage repair with similar reparation capacity than chondrocytes.

A Randomized Clinical Trial to Evaluate Two Doses of an Intra-Articular Injection of LMWF-5A in Adults with Pain Due to Osteoarthritis of the Knee

PubMed Central

Bar-Or, David; Salottolo, Kristin M.; Loose, Holli; Phillips, Matthew J.; McGrath, Brian; Wei, Nathan; Borders, James L.; Ervin, John E.; Kivitz, Alan; Hermann, Mark; Shlotzhauer, Tammi; Churchill, Melvin; Slappey, Donald; Clift, Vaughan

2014-01-01

Objective The Low Molecular Weight Fraction of 5% human serum Albumin (LMWF-5A) is being investigated as a treatment for knee pain from osteoarthritis. Methods This was a multicenter randomized, vehicle-controlled, double-blind, parallel study designed to evaluate the safety and efficacy of two doses of an intra-articular injection of LMWF-5A. Patients with symptomatic knee osteoarthritis were randomized 1∶1∶1∶1 to receive a single 4 mL or 10 mL intra-articular knee injection of either LMWF-5A or vehicle control (saline). The primary efficacy endpoint was the difference between treatment groups in the Western Ontario and McMaster Universities (WOMAC) pain change from baseline over 12 weeks. Safety was examined as the incidence and severity of adverse events (AEs). Results A total of 329 patients were randomized and received treatment. LMWF-5A resulted in a significant decrease in pain at 12 weeks compared to vehicle control (−0.93 vs −0.72; estimated difference from control: −0.25, p = 0.004); an injection volume effect was not observed (p = 0.64). The effect of LMWF-5A on pain was even more pronounced in patients with severe knee OA (Kellgren Lawrence Grade IV): the estimated difference from control was −0.42 (p = 0.02). Adverse events were generally mild and were similar in patients who received vehicle control (47%) and LMWF-5A (41%). Conclusions This clinical trial demonstrated that LMWF-5A is safe and effective at providing relief for the pain of moderate to severe OA of the knee over 12 weeks when administered by intra-articular injection into the knee. Trial Registration ClinicalTrials.gov NCT01839331 PMID:24498399

[Meniscoids of the intervertebral joints].

PubMed

Kos, J; Hert, J; Sevcík, P

2002-01-01

A large amount of material was used to study the distribution, location and shape of meniscoids in intervertebral joints of the human spine, from the atlanto-occipital joint to the sacrum, in order to find out how many of intervertebral joints had mobile meniscoids. These might be regarded as possible causes of spinal blockade or other vertebrogenous complaints. The materials provided by the Department of Anatomy and Department of Forensic Medicine at the Faculty of Medicine of Charles University in Pilznen included 20 cadaverous spines from humans aged 20 to 80 years. Access to each joint was provided by dissection of the articular capsule from the lower articular processes of the vertebra situated above. In the orthograde view, all meniscoids were described in terms of shape, size, consistence and location. Their structure was ascertained by histological examination of cross sections stained with haematoxylin and eosin. Meniscoids varying in shape and size were found in all of the intervertebral joints. They were classified by their histological structure as synovial, fat and fibrous meniscoids. The first category was observed frequently, the last only rarely. A total of 29 mobile meniscoids were recorded, most of them in the lumbar spine. Most of the meniscoids present in the cervical spine were of synovial and less frequently of fat types. Meniscoids found in the thoracic spine were poorly developed synovial ones and those present in the lumbar spine were of all types and were also largest in size. The most conspicuous meniscoids were seen in the spines that showed degenerative changes in intervertebral joints. Large fat pads were found in atlanto-occipital and atlanto-axial joints. Mobile meniscoids, most of them present in the lumbar spine (6.4% of all joints.), were connected with the capsule by a thin pedicle and it was possible to move them over a half of the articular surface. Some inter-individual changes were also found; in some spines, the most developed meniscoids were fat pads, in the others, these were synovial meniscoids. Spines of younger individuals showed a predominance of synovial meniscoids with smooth surfaces that arched against the articular cavity. In spines of elderly individuals, meniscoids were rough, in some cases fibrous in structure, and had a lobulated or frayed edge. The shape, location of meniscoids and their presence in every joint indicate their definite role for the spine: they compensate the incongruence of articular surfaces, fill in empty spaces and facilitate spread of synovial fluid during translation movements. Variability in shape, size and location of meniscoids give support to the view that meniscoids developed secondarily in relation to the morphogenesis of articular surfaces and that they are fully adapted to the shape and function of the joint. Mobile meniscoids, particularly fibrous ones, can get wedged between articular surfaces due to a sudden, rush movement (entrapment theory) or can be caught between the edge of an articular surface and the articular capsule attachment (extrapment theory). This situation may result in either mechanical or functional blockade of the spine and a subsequent painful condition due to compression of nerves and reflex contraction of muscles. Direct evidence of such blockade and the validity of either hypothesis can today be provided by magnetic resonance imaging. All intervertebral joints, along the length of spine, possess capsule processes, i.e., meniscoids, which can be classified as synovial, fat and fibrous. Meniscoids are most developed in the lumbar and cervical spine. They serve to compensate for the incongruence of articular surfaces and to fill in empty spaces. Mobile, peduncular meniscoids can, at sudden or non-physiological movements, be caught between articular surfaces and cause spinal blockade and painful conditions. Manipulative treatment is, therefore, justified in indicated cases.

Locating articular cartilage in MR images

NASA Astrophysics Data System (ADS)

Folkesson, Jenny; Dam, Erik; Pettersen, Paola; Olsen, Ole F.; Nielsen, Mads; Christiansen, Claus

2005-04-01

Accurate computation of the thickness of the articular cartilage is of great importance when diagnosing and monitoring the progress of joint diseases such as osteoarthritis. A fully automated cartilage assessment method is preferable compared to methods using manual interaction in order to avoid inter- and intra-observer variability. As a first step in the cartilage assessment, we present an automatic method for locating articular cartilage in knee MRI using supervised learning. The next step will be to fit a variable shape model to the cartilage, initiated at the location found using the method presented in this paper. From the model, disease markers will be extracted for the quantitative evaluation of the cartilage. The cartilage is located using an ANN-classifier, where every voxel is classified as cartilage or non-cartilage based on prior knowledge of the cartilage structure. The classifier is tested using leave-one-out-evaluation, and we found the average sensitivity and specificity to be 91.0% and 99.4%, respectively. The center of mass calculated from voxels classified as cartilage are similar to the corresponding values calculated from manual segmentations, which confirms that this method can find a good initial position for a shape model.

Novel bioadhesive polymers as intra-articular agents: Chondroitin sulfate-cysteine conjugates.

PubMed

Suchaoin, Wongsakorn; Bonengel, Sonja; Griessinger, Julia Anita; Pereira de Sousa, Irene; Hussain, Shah; Huck, Christian W; Bernkop-Schnürch, Andreas

2016-04-01

The aim of this study was to generate and characterize a chondroitin sulfate-cysteine conjugate (CS-cys) as a novel bioadhesive agent for intra-articular use. Mucoadhesive properties of synthesized CS-cys were investigated by rheological measurement of polymer-mucus mixture and rotating cylinder method, while bioadhesive features of CS-cys on porcine articular cartilage were evaluated via tensile studies. Thiolation was achieved by attachment of l-cysteine to CS via amide bond formation mediated by carbodiimide as a coupling reagent. The conjugate exhibited 421.17±35.14 μmol free thiol groups per gram polymer. The reduced CS-cys displayed 675.09±39.67 μmol free thiol groups per gram polymer after disulfide bonds reduction using tris(2-carboxyethyl)phosphine hydrochloride. The increase in dynamic viscosity of thiolated CS due to oxidative disulfide bond formation was demonstrated using capillary viscometer. The combination of CS-cys and mucus led to 4.57-fold increase in dynamic viscosity in comparison with mucus control. Furthermore, adhesion time to porcine mucosa of CS-cys-based test disk was enhanced by 2.48-fold compared to unmodified CS as measured by rotating cylinder method suggesting the interaction between thiomers and mucus gel layer via disulfide bonds formation. Tensile studies of thiolated CS on porcine articular cartilage showed 5.37- and 1.76-fold increase in the total work of adhesion and the maximum detachment force, respectively, in comparison with unmodified CS indicating bioadhesive features of CS-cys. Cytotoxicity of CS-cys was assessed in Caco-2 cells and rat primary articular chondrocytes using MTT and LDH release assay, thereby showing the safety of CS-cys at a concentration of 0.25% (w/v) in Caco-2 cells. Furthermore, 0.1% of CS-cys was found non-toxic to rat primary articular chondrocytes. According to these results, CS-cys provides improved bioadhesive properties that might be useful as an intra-articular agent for treatment of osteoarthritis. Copyright © 2016 Elsevier B.V. All rights reserved.

Customized Fabrication of Osteochondral Tissue for Articular Joint Surface Repair

DTIC Science & Technology

2016-09-01

differentiation cues for chondrogenesis and osteogenesis, by the 3D printing method of projection stereolithography (PSL). We further test the...military medical care costs. Post Traumatic Osteoarthritis, Injury, Articular Cartilage, tissue-engineered, 3D printing , Osteochondral constructs. Major...tissue with the stem cells used. He will also be assisting with the 3D printing of the material. Funding Support: Supported by internal University

Reduction and internal fixation of displaced intra-articular calcaneal fractures with a locking nail: a prospective study of sixty nine cases.

PubMed

Simon, P; Goldzak, M; Eschler, A; Mittlmeier, T

2015-10-01

The best treatment for intra-articular fractures of the calcaneus is still debated. The aims of this study were to determine whether intrafocal reduction of thalamic fractures is effective, to evaluate whether a locking nail is able to maintain reduction of the articular surface and to analyse the functional results of this original method. This prospective study assessed 69 fractures treated with a locking fracture nail in 63 cases and with primary subtalar fusion in six (Calcanail (®), FH). Articular congruity and global reduction of the calcaneus was assessed in all patients by computed tomography (CT) scan three months postoperatively. Functional results were evaluated according to the American Orthopaedic Foot and Ankle Society Ankle-Hindfoot Score (AOFAS-AHS) and all complications recorded. For the 63 fracture nails, the average AOFAS score was 85.9 at a mean final follow-up of 12 months. Only three secondary fusions were performed. For the six comminuted fractures requiring primary fusion, the average AOFAS score was 75.9 at the last follow-up. The posterior intrafocal approach for both reduction and locked nailing of intra-articular calcaneal fractures has been proven as an effective and reliable procedure.

Isotropic morphometry and multicomponent T1 ρ mapping of human knee articular cartilage in vivo at 3T.

PubMed

Baboli, Rahman; Sharafi, Azadeh; Chang, Gregory; Regatte, Ravinder R

2018-05-02

The progressive loss of hyaline articular cartilage due to osteoarthritis (OA) changes the functional and biochemical properties of cartilage. Measuring the T 1 ρ along with the morphological assessment can potentially be used as noninvasive biomarkers in detecting early-stage OA. To correlate the biochemical and morphological data, submillimeter isotropic resolution for both studies is required. To implement a high spatial resolution 3D-isotropic-MRI sequence for simultaneous assessment of morphological and biexponential T 1 ρ relaxometry of human knee cartilage in vivo. Prospective. Ten healthy volunteers with no known inflammation, trauma, or pain in the knee. Standard FLASH sequence and customized Turbo-FLASH sequence to acquire 3D-isotropic-T 1 ρ-weighted images on a 3T MRI scanner. The mean volume and thickness along with mono- and biexponential T 1 ρ relaxations were assessed in the articular cartilage of 10 healthy volunteers. Nonparametric rank-sum tests. Bland-Altman analysis and coefficient of variation. The mean monoexponential T 1 ρ relaxation was 40.7 ± 4.8 msec, while the long and short components were 58.2 ± 3.9 msec and 6.5 ± 0.6 msec, respectively. The mean fractions of long and short T 1 ρ relaxation components were 63.7 ± 5.9% and 36.3 ± 5.9%, respectively. Statistically significant (P ≤ 0.03) differences were observed in the monoexponential and long components between some of the regions of interest (ROIs). No gender differences between biexponential components were observed (P > 0.05). Mean cartilage volume and thickness were 25.9 ± 6.4 cm 3 and 2.2 ± 0.7 mm, respectively. Cartilage volume (P = 0.01) and thickness (P = 0.03) were significantly higher in male than female participants across all ROIs. Bland-Altman analysis showed agreement between two morphological methods with limits of agreement between -1000 mm 3 and +1100 mm 3 for volume, and -0.78 mm and +0.46 mm for thickness, respectively. Simultaneous assessment of morphological and multicomponent T 1 ρ relaxation of knee joint with 0.7 × 0.7 × 0.7 mm isotropic spatial resolution is demonstrated in vivo. Comparison with a standard method showed that the proposed technique is suitable for assessing the volume and thickness of articular cartilage. 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;00:000-000. © 2018 International Society for Magnetic Resonance in Medicine.

Human YKL39 (chitinase 3-like protein 2), an osteoarthritis-associated gene, enhances proliferation and type II collagen expression in ATDC5 cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miyatake, Kazumasa; Tsuji, Kunikazu, E-mail: ktsuji.gcoe@tmd.ac.jp; Yamaga, Mika

Highlights: ► hYKL-39 expression is increased in osteoarthritic articular chondrocytes. ► To examine the molecular functions of hYKL-39 in chondrocytes, we overexpressed hYKL-39 in chondrocytic ATDC5 cells. ► hYKL-39 enhanced proliferation and colony formation in ATDC5 cells. ► hYKL-39 increased type II collagen expression in ATDC5 cells treated with chondrogenic medium. -- Abstract: Human YKL39 (chitinase 3-like protein 2/CHI3L2) is a secreted 39 kDa protein produced by articular chondrocytes and synoviocytes. Recent studies showed that hYKL-39 expression is increased in osteoarthritic articular chondrocytes suggesting the involvement of hYKL-39 in the progression of osteoarthritis (OA). However little is known regarding themore » molecular function of hYKL-39 in joint homeostasis. Sequence analyses indicated that hYKL-39 has significant identity with the human chitotorisidase family molecules, although it is considered that hYKL-39 has no enzymatic activity since it lacks putative chitinase catalytic motif. In this study, to examine the molecular function of hYKL-39 in chondrocytes, we overexpressed hYKL-39 in ATDC5 cells. Here we report that hYKL-39 enhances colony forming activity, cell proliferation, and type II collagen expression in these cells. These data suggest that hYKL-39 is a novel growth and differentiation factor involved in cartilage homeostasis.« less

Analysis of human articular chondrocyte CD44 isoform expression and function in health and disease.

PubMed

Salter, D M; Godolphin, J L; Gourlay, M S; Lawson, M F; Hughes, D E; Dunne, E

1996-08-01

Interactions between articular chondrocytes and components of the extracellular matrix are of potential importance in the normal function of cartilage and in the pathophysiology of arthritis. Little is known of the basis of these interactions, but cell adhesive molecules such as CD44 are likely to be involved. Immunohistology using six well-characterized anti-CD44 monoclonal antibodies demonstrated standard CD44 isoform (CD44H) expression by all chondrocytes in normal and osteoarthrotic (OA) cartilage but absence of the CD44E variant. Polymerase chain reaction (PCR) of reverse transcribed mRNA from monolayer cultures of normal and OA chondrocytes using primer sequences which span the region containing variably spliced exons produced a predominant band representing the standard form of CD44, which lacks the variable exons 6-15 (v1-v10). No product was seen at the expected size of the epithelial variant of CD44 (CD44v8-10). Use of exon-specific primers, however, showed expression of variant exons resulting in multiple minor isoforms. Standard CD44 was also shown to be the predominantly expressed isoform identified by immunoprecipitation, but human articular chondrocytes did not adhere to hyaluronan in vitro. Chondrocyte CD44 may function as an adhesion receptor for other matrix molecules such as fibronectin or collagen.

Chondrocyte heterogeneity: immunohistologically defined variation of integrin expression at different sites in human fetal knees.

PubMed

Salter, D M; Godolphin, J L; Gourlay, M S

1995-04-01

During development and at maturity different forms of cartilage vary in morphology and macromolecular content. This reflects heterogeneity of chondrocyte activity, in part involving differential interactions with the adjacent extracellular matrix via specialized cell surface receptors such as integrins. We undertook an immunohistological study on a series of human fetal knee joints to assess variation in the expression of integrins by chondrocytes and potential matrix ligands in articular, epiphyseal, growth plate, and meniscal cartilage. The results show that articular chondrocytes (beta 1+, beta 5 alpha V+, alpha 1+, alpha 2+/-, alpha 5+, weakly alpha 6+, alpha V+) differed from epiphyseal (beta 1+, beta 5 alpha V+, alpha 1+/-, alpha 2+/-, alpha 5+, alpha 6+, alpha V+) growth plate (beta 1+, beta 5 alpha V+, alpha 1-, alpha 2-, alpha 5+, alpha 6+, alpha V+), and meniscal cells (beta 1+, beta 5 alpha V+, alpha 1+, strongly alpha 2+, alpha 5+, alpha 6+, alpha V+ in expression of integrin subunits. There was no expression of beta 3, beta 4, beta 6, or alpha 3 by chondrocytes. These results differ from previous reports on the expression of integrins by adult articular cartilage, where alpha 2 and alpha 6 are not seen. Variation in distribution of matrix ligands was also seen. Fibronectin, laminin and Type VI collagen were expressed in all cartilages but there was restricted expression of tenascin, ED-A and ED-B fibronectin isoforms (articular cartilage and meniscus), and vitronectin (absent from growth plate cartilage). Regulated expression of integrins by chondrocytes, associated with changes in the pericellular matrix composition, is of potential importance in control of cartilage differentiation and function in health and disease.

INTRA-ARTICULAR NERVE GROWTH FACTOR REGULATES DEVELOPMENT, BUT NOT MAINTENANCE, OF INJURY-INDUCED FACET JOINT PAIN & SPINAL NEURONAL HYPERSENSITIVITY

PubMed Central

Kras, Jeffrey V.; Kartha, Sonia; Winkelstein, Beth A.

2015-01-01

Objective The objective of the current study is to define whether intra-articular nerve growth factor (NGF), an inflammatory mediator that contributes to osteoarthritic pain, is necessary and sufficient for the development or maintenance of injury-induced facet joint pain and its concomitant spinal neuronal hyperexcitability. Method Male Holtzman rats underwent painful cervical facet joint distraction or sham procedures. Mechanical hyperalgesia was assessed in the forepaws, and NGF expression was quantified in the C6/C7 facet joint. An anti-NGF antibody was administered intra-articularly in additional rats immediately or 1 day following facet distraction or sham procedures to block intra-articular NGF and test its contribution to initiation and/or maintenance of facet joint pain and spinal neuronal hyperexcitability. NGF was injected into the bilateral C6/C7 facet joints in separate rats to determine if NGF alone is sufficient to induce these behavioral and neuronal responses. Results NGF expression increases in the cervical facet joint in association with behavioral sensitivity after that joint’s mechanical injury. Intra-articular application of anti-NGF immediately after a joint distraction prevents the development of both injury-induced pain and hyperexcitability of spinal neurons. Yet, intra-articular anti-NGF applied after pain has developed does not attenuate either behavioral or neuronal hyperexcitability. Intra-articular NGF administered to the facet in naïve rats also induces behavioral hypersensitivity and spinal neuronal hyperexcitability. Conclusion Findings demonstrate that NGF in the facet joint contributes to the development of injury-induced joint pain. Localized blocking of NGF signaling in the joint may provide potential treatment for joint pain. PMID:26521746

Decreasing cartilage damage in a rat model of osteoarthritis by intra-articular injection of deoxycholic acid

PubMed Central

Yan, Zhaowei; Xiong, Jianbin; Zhao, Chunyang; Qin, Chenhao; He, Chunyan

2015-01-01

Background: The aim of this experimental study was to evaluate the effect of intra-articular injection of Deoxycholic acid (DCA) on articular cartilage and subchondral bone following induction of knee Osteoarthritis (OA) in a rat model. Methods: Twenty-four Sprague Dawley rats were randomized divided into 4 groups (n = 6). Eighteen of the 24 rats underwent surgical destabilization of the medial meniscus on the right knee joints to induce OA, were divided into 3 groups: DCA 30 mg/kg group, DCA 120 mg/kg group and OA group. The rats in DCA-treated groups were given intra-articular injections of DCA (30 mg/kg or 120 mg/kg) in the operated knees once per 3 days for 42 days. The rats in OA group given intra-articular injections of vehicle alone in the operated knees under the same conditions. The remaining 6 rats (sham-operation group) received sham operations on the right knee joints. 45 days postoperatively, all of the animals were euthanized for macroscopic, histological and radiographic analysis to evaluate the effect of DCA on OA and to determine its potential mechanisms. Results: The results showed that DCA attenuated the severity of OA by reducing macroscopic observation sores for femoral condyles and histological sores for articular cartilage. DCA also significantly decreased bone destruction and erosion of joint evaluated by radiographic examination. Furthermore, DCA could markedly reduce the release of MMP-1, MMP-3 and IL-1β in serum. Conclusions: Intra-articular injection of DCA is beneficial for knee OA. It might repair and protect OA cartilage by delaying cartilage degeneration and impairing the function of inflammatory mediators. These findings highlight DCA might be a useful therapeutic agent for OA. PMID:26309557

Magnetic resonance imaging for diagnosis and assessment of cartilage defect repairs.

PubMed

Marlovits, Stefan; Mamisch, Tallal Charles; Vekszler, György; Resinger, Christoph; Trattnig, Siegfried

2008-04-01

Clinical magnetic resonance imaging (MRI) is the method of choice for the non-invasive evaluation of articular cartilage defects and the follow-up of cartilage repair procedures. The use of cartilage-sensitive sequences and a high spatial-resolution technique enables the evaluation of cartilage morphology even in the early stages of disease, as well as assessment of cartilage repair. Sequences that offer high contrast between articular cartilage and adjacent structures, such as the fat-suppressed, 3-dimensional, spoiled gradient-echo sequence and the fast spin-echo sequence, are accurate and reliable for evaluating intrachondral lesions and surface defects of articular cartilage. These sequences can also be performed together in reasonable examination times. In addition to morphology, new MRI techniques provide insight into the biochemical composition of articular cartilage and cartilage repair tissue. These techniques enable the diagnosis of early cartilage degeneration and help to monitor the effect and outcome of various surgical and non-surgical cartilage repair therapies.

Arthroscopic study of injuries in articular fractures of distal radius extremity

PubMed Central

Araf, Marcelo; Mattar, Rames

2014-01-01

OBJECTIVE: To analyze the incidence of wrist ligament and cartilage associated fractures of the distal radius, through arthroscopy, correlating with AO/ASIF classification. METHODS: Thirty patients aged between 20 and 50 years old, with closed fracture from groups B and C according to AO/ASIF classification were selected. All of them were submitted to wrist arthroscopy to address intra-articular injuries and reduction and osteosynthesis of the fracture. RESULTS: A high incidence of intra-articular injuries was noticed, and 76.6% of them presented injury of the triangular fibrocartilage complex, 36.6% of the intrinsic scapholunate ligament, 6.6% of the intrinsic triquetrolunate ligament, and 33% articular cartilage injury larger than three millimeters. Patients with fractures from type C according to AO/ASIF classification presented a higher incidence of ligament injuries. CONCLUSION: There is no relationship between the presence of chondral injury and the AO/ASIF classification of the fractures in the cases reported in this study. Level of Evidence III, Non Randomized Controlled Trial. PMID:25061421

Intra-articular administration of lidocaine in anaesthetized dogs: pharmacokinetic profile and safety on cardiovascular and nervous systems.

PubMed

Di Salvo, A; Bufalari, A; De Monte, V; Cagnardi, P; Marenzoni, M L; Catanzaro, A; Vigorito, V; Della Rocca, G

2015-08-01

The intra-articular administration of lidocaine is a frequent practice in human orthopaedic surgical procedures, but an eventual absorption of the drug into the bloodstream can lead to toxicity, mainly concerning the central nervous system and the cardiovascular systems. The purpose of this study was to determine the pharmacokinetic profile and the safety, in terms of cardiovascular and CNS toxicity, of lidocaine after intra-articular administration to anesthetized dogs undergoing arthroscopy. Lidocaine 2% was administered to eight dogs before surgery in differing amounts, depending on the volume of the joints involved, and blood samples were taken at predetermined time points. The maximum serum concentration of lidocaine ranged from 0.50 to 3.01 μg/mL (mean ± SD: 2.18 ± 0.91 μg/mL), and the time to reach it was 28.75 ± 15.74 min. No signs of cardiac toxicity were detected during the entire procedure, and possible signs of CNS toxicity were masked by the anaesthesia. However, concentrations reported in literature as responsible for neurotoxicity in dog were achieved in three of eight investigated subjects. Pending further studies, veterinarians should consider the possibility of side effects occurring following the intra-articular administration of local anaesthetics. © 2014 John Wiley & Sons Ltd.

Trabecular trajectory in the articular processes of the human fourth cervical vertebra

PubMed Central

HERRERA, M.; PANCHÓN, A.; PEREZ-BACETE, M.

2001-01-01

The articular processes (AP) of the neural arch have been implicated in weight transmission through the cervical spine. To analyse the mechanism of weight transmission in the AP, we studied the direction of forces within it, in particular, the pattern of trabecular trajectories. Twenty-two AP from C4 vertebrae were studied in anatomical sections, and corresponding photoelastic models from selected sections were constructed and analysed. Anatomical and photoelastic findings show the subarticular spongiosa of the superior articular process (SAP) to be orthogonally arranged with vertical and oblique trabeculae in the direction of compressive forces and additional trabeculae always oriented perpendicular to the former. Vertical and oblique trabeculae are divided into rostral, middle and posterior groups. Rostral and middle trabeculae end in the anterior wall of the SAP and the transitional zone with the pedicle. Posterior trabeculae end in the subarticular spongiosa of the inferior articular process (IAP). The findings relating to trabecular trajectories in the SAP differ from previous descriptions and instead suggest that a part of the weight forces distributed within the AP transmit to the subchondral zone of the IAP. Knowledge of the trajectorial architecture of the AP may contribute to refining finite element analytical models for investigating its weight-bearing function. PMID:11554512

Physiological loading of joints prevents cartilage degradation through CITED2.

PubMed

Leong, Daniel J; Li, Yong H; Gu, Xiang I; Sun, Li; Zhou, Zuping; Nasser, Philip; Laudier, Damien M; Iqbal, Jameel; Majeska, Robert J; Schaffler, Mitchell B; Goldring, Mary B; Cardoso, Luis; Zaidi, Mone; Sun, Hui B

2011-01-01

Both overuse and disuse of joints up-regulate matrix metalloproteinases (MMPs) in articular cartilage and cause tissue degradation; however, moderate (physiological) loading maintains cartilage integrity. Here, we test whether CBP/p300-interacting transactivator with ED-rich tail 2 (CITED2), a mechanosensitive transcriptional coregulator, mediates this chondroprotective effect of moderate mechanical loading. In vivo, hind-limb immobilization of Sprague-Dawley rats up-regulates MMP-1 and causes rapid, histologically detectable articular cartilage degradation. One hour of daily passive joint motion prevents these changes and up-regulates articular cartilage CITED2. In vitro, moderate (2.5 MPa, 1 Hz) intermittent hydrostatic pressure (IHP) treatment suppresses basal MMP-1 expression and up-regulates CITED2 in human chondrocytes, whereas high IHP (10 MPa) down-regulates CITED2 and increases MMP-1. Competitive binding and transcription assays demonstrate that CITED2 suppresses MMP-1 expression by competing with MMP transactivator, Ets-1 for its coactivator p300. Furthermore, CITED2 up-regulation in vitro requires the p38δ isoform, which is specifically phosphorylated by moderate IHP. Together, these studies identify a novel regulatory pathway involving CITED2 and p38δ, which may be critical for the maintenance of articular cartilage integrity under normal physical activity levels.

Perivascular Mesenchymal Stem Cells in Sheep: Characterization and Autologous Transplantation in a Model of Articular Cartilage Repair.

PubMed

Hindle, Paul; Baily, James; Khan, Nusrat; Biant, Leela C; Simpson, A Hamish R; Péault, Bruno

2016-11-01

Previous research has indicated that purified perivascular stem cells (PSCs) have increased chondrogenic potential compared to conventional mesenchymal stem cells (MSCs) derived in culture. This study aimed to develop an autologous large animal model for PSC transplantation and to specifically determine if implanted cells are retained in articular cartilage defects. Immunohistochemistry and fluorescence-activated cell sorting were used to ascertain the reactivity of anti-human and anti-ovine antibodies, which were combined and used to identify and isolate pericytes (CD34 - CD45 - CD146 + ) and adventitial cells (CD34 + CD45 - CD146 - ). The purified cells demonstrated osteogenic, adipogenic, and chondrogenic potential in culture. Autologous ovine PSCs (oPSCs) were isolated, cultured, and efficiently transfected using a green fluorescence protein (GFP) encoding lentivirus. The cells were implanted into articular cartilage defects on the medial femoral condyle using hydrogel and collagen membranes. Four weeks following implantation, the condyle was explanted and confocal laser scanning microscopy demonstrated the presence of oPSCs in the defect repaired with the hydrogel. These data suggest the testability in a large animal of native MSC autologous grafting, thus avoiding possible biases associated with xenotransplantation. Such a setting will be used in priority for indications in orthopedics, at first to model articular cartilage repair.

Navigation-Assisted Total Knee Arthroplasty for Patients with Extra-Articular Deformity

PubMed Central

Rhee, Seung Joon; Seo, Chang Hyo

2013-01-01

Purpose Since the existence of an extra-articular deformity seriously alters the normal geometry and kinetics around the knee joint, difficulties are often encountered in total knee arthroplasty (TKA) using a standard surgical technique. The purpose of this study was to evaluate the usefulness of surgical navigation system as a treatment option for osteoarthritic knees with extra-articular deformity. Materials and Methods The authors retrospectively reviewed medical records of the patients who underwent primary TKA between 2007 and 2012. Knees with preoperative radiography showing an angular deformity within the region from the middle third of the femur to the middle third of the tibia in the ipsilateral limb of the arthritic knees were considered as cases having extra-articular deformity. Thirteen knees of the 13 patients were found to have undergone TKA using a navigation system for osteoarthritis with ipsilateral extra-articular deformity. The hip-knee-ankle angle, Knee Society score (KSS), and range of motion were measured before and after the operation to evaluate the improvement. Results The mean hip-knee-ankle angle in the coronal plane was improved to 0.2°±4.5° in valgus alignment postoperatively. The KSS was improved to 89.6±4.6 points postoperatively at the last follow-up, with over 90% of good and excellent results. The range of motion was improved to 118.5°±10.5° postoperatively. Conclusions Navigation-assisted TKA is a good treatment option of osteoarthritic knees with extra-articular deformity. PMID:24368997

Comparative effectiveness of intra-articular prolotherapy versus peri-articular prolotherapy on pain reduction and improving function in patients with knee osteoarthritis: A randomized clinical trial.

PubMed

Farpour, Hamid Reza; Fereydooni, Farzane

2017-11-01

Osteoarthritis is a common degenerative disease. Prolotherapy is an alternative therapy used in multiple musculoskeletal disorders. To compare the effectiveness of intra-articular dextrose injection versus peri-articular prolotherapy in patients with knee osteoarthritis (KOA). Fifty-two adults with painful primary knee osteoarthritis for at least three months were randomized to intra- and peri-articular injection groups. Prolotherapy was done twice with two week intervals. The outcome measures included the Oxford Knee Scale (OKS), Western Ontario McMaster University Osteoarthritis Index (WOMAC), and Visual Analogue Scale (VAS), which were obtained from patients before the first injection at the base line and after the second injection at the fourth and eighth weeks. There were no statistically significant differences between demographic characteristics; before the injection, pain intensity, OKS, and WOMAC scores were approximately equal between the two groups. After dextrose prolotherapy, VAS, OKS, and WOMAC scores improved from baseline through the fourth and eighth weeks in both groups without any superiority between the two methods of injections (p<0.001). Dextrose prolotherapy either intra- or peri-articular injection resulted in significant improvement, so it could be an inexpensive and effective management of knee osteoarthritis. The study protocol was registered as a clinical trial under registration ID of IRCT2016091229795N1 at the Iranian Registry of Clinical Trials (http://www.irct.ir). The authors received no financial support for the research, authorship, or publication of this article.

Toward patient-specific articular contact mechanics

PubMed Central

Ateshian, Gerard A.; Henak, Corinne R.; Weiss, Jeffrey A.

2015-01-01

The mechanics of contacting cartilage layers is fundamentally important to understanding the development, homeostasis and pathology of diarthrodial joints. Because of the highly nonlinear nature of both the materials and the contact problem itself, numerical methods such as the finite element method are typically incorporated to obtain solutions. Over the course of five decades, we have moved from an initial qualitative understanding of articular cartilage material behavior to the ability to perform complex, three-dimensional contact analysis, including multiphasic material representations. This history includes the development of analytical and computational contact analysis methods that now provide the ability to perform highly nonlinear analyses. Numerical implementations of contact analysis based on the finite element method are rapidly advancing and will soon enable patient-specific analysis of joint contact mechanics using models based on medical image data. In addition to contact stress on the articular surfaces, these techniques can predict variations in strain and strain through the cartilage layers, providing the basis to predict damage and failure. This opens up exciting areas for future research and application to patient-specific diagnosis and treatment planning applied to a variety of pathologies that affect joint function and cartilage homeostasis. PMID:25698236

Glucosamine Activates Autophagy In Vitro and In Vivo

PubMed Central

Caramés, Beatriz; Kiosses, William B.; Akasaki, Yukio; Brinson, Diana C.; Eap, William; Koziol, James; Lotz, Martin K.

2013-01-01

Objectives Aging-associated changes in articular cartilage represent a main Osteoarthritis (OA) risk factor. Autophagy is an essential cellular homeostasis mechanism. Aging-associated or experimental defects in autophagy contribute to organismal and tissue specific aging while enhancement of autophagy may protect against certain aging related pathologies such as OA. The objective of this study was to determine whether glucosamine (GlcN) could activate autophagy. Methods Chondrocytes from normal human articular cartilage were treated with GlcN (0.1-10 mM). Autophagy activation and phosphorylation levels of Akt, FoxO3 and ribosomal protein S6 (prbS6) were determined by Western blotting. Autophagosome formation was analyzed by microscopy. Transgenic reporter mice with green fluorescent protein fused to LC3 (GFP-LC3 mice) were used to test changes in autophagy in response to starvation and GlcN administration. Results GlcN treatment of chondrocytes activated autophagy as indicated by increased of LC3-II levels, formation of LC3 puncta and increased LC3 turnover. This was associated with GlcN-mediated inhibition of Akt, FoxO3 and mTOR pathway. Administration of GlcN to GFP-LC3 mice markedly activated autophagy in articular cartilage. Conclusions GlcN modulates molecular targets of the autophagy pathway in vitro and in vivo and the enhancement of autophagy was mainly dependent on the Akt/FoxO and mTOR pathway. These findings suggest that GlcN is an effective autophagy activator and motivate future studies on its efficacy in modifying aging-related cellular changes and supporting joint health. PMID:23606170

Mechanical testing of hydrogels in cartilage tissue engineering: beyond the compressive modulus.

PubMed

Xiao, Yinghua; Friis, Elizabeth A; Gehrke, Stevin H; Detamore, Michael S

2013-10-01

Injuries to articular cartilage result in significant pain to patients and high medical costs. Unfortunately, cartilage repair strategies have been notoriously unreliable and/or complex. Biomaterial-based tissue-engineering strategies offer great promise, including the use of hydrogels to regenerate articular cartilage. Mechanical integrity is arguably the most important functional outcome of engineered cartilage, although mechanical testing of hydrogel-based constructs to date has focused primarily on deformation rather than failure properties. In addition to deformation testing, as the field of cartilage tissue engineering matures, this community will benefit from the addition of mechanical failure testing to outcome analyses, given the crucial clinical importance of the success of engineered constructs. However, there is a tremendous disparity in the methods used to evaluate mechanical failure of hydrogels and articular cartilage. In an effort to bridge the gap in mechanical testing methods of articular cartilage and hydrogels in cartilage regeneration, this review classifies the different toughness measurements for each. The urgency for identifying the common ground between these two disparate fields is high, as mechanical failure is ready to stand alongside stiffness as a functional design requirement. In comparing toughness measurement methods between hydrogels and cartilage, we recommend that the best option for evaluating mechanical failure of hydrogel-based constructs for cartilage tissue engineering may be tensile testing based on the single edge notch test, in part because specimen preparation is more straightforward and a related American Society for Testing and Materials (ASTM) standard can be adopted in a fracture mechanics context.

MRI-based hip cartilage measures in osteoarthritic and non-osteoarthritic individuals: a systematic review

PubMed Central

Aguilar, Hector N; Battié, Michele C

2017-01-01

Osteoarthritis is a common hip joint disease, involving loss of articular cartilage. The prevalence and prognosis of hip osteoarthritis have been difficult to determine, with various clinical and radiological methods used to derive epidemiological estimates exhibiting significant heterogeneity. MRI-based methods directly visualise hip joint cartilage, and offer potential to more reliably define presence and severity of osteoarthritis, but have been underused. We performed a systematic review of MRI-based estimates of hip articular cartilage in the general population and in patients with established osteoarthritis, using MEDLINE, EMBASE and SCOPUS current to June 2016, with search terms such as ‘hip’, ‘femoral head’, ‘cartilage’, ‘volume’, ‘thickness’, ‘MRI’, etc. Ultimately, 11 studies were found appropriate for inclusion, but they were heterogeneous in osteoarthritis assessment methodology and composition. Overall, the studies consistently demonstrate the reliability and potential clinical utility of MRI-based estimates. However, no longitudinal data or reference values for hip cartilage thickness or volume have been published, limiting the ability of MRI to define or risk-stratify hip osteoarthritis. MRI-based techniques are available to quantify articular cartilage signal, volume, thickness and defects, which could establish the sequence and rate of articular cartilage changes at the hip that yield symptomatic osteoarthritis. However, prevalence and rates of progression of hip osteoarthritis have not been established in any MRI studies in the general population. Future investigations could fill this important knowledge gap using robust MRI methods in population-based cross-sectional and longitudinal studies. PMID:28405471

Articular cartilage generation applying PEG-LA-DM/PEGDM copolymer hydrogels.

PubMed

Zhao, Xing; Papadopoulos, Anestis; Ibusuki, Shinichi; Bichara, David A; Saris, Daniel B; Malda, Jos; Anseth, Kristi S; Gill, Thomas J; Randolph, Mark A

2016-06-03

Injuries to the human native cartilage tissue are particularly problematic because cartilage has little to no ability to heal or regenerate itself. Employing a tissue engineering strategy that combines suitable cell sources and biomimetic hydrogels could be a promising alternative to achieve cartilage regeneration. However, the weak mechanical properties may be the major drawback to use fully degradable hydrogels. Besides, most of the fully degradable hydrogels degrade too fast to permit enough extracellular matrix (ECM) production for neocartilage formation. In this study, we demonstrated the feasibility of neocartilage regeneration using swine articular chondrocytes photoencapsualted into poly (ethylene glycol) dimethacrylate (PEGDM) copolymer hydrogels composed of different degradation profiles: degradable (PEG-LA-DM) and nondegradable (PEGDM) macromers in molar ratios of 50/50, 60/40, 70/30, 80/20, and 90/10. Articular chondrocytes were isolated enzymatically from juvenile Yorkshire swine cartilage. 6 × 10(7) cells cells were added to each milliliter of macromer/photoinitiator (I2959) solution. Nonpolymerized gel containing the cells (100 μL) was placed in cylindrical molds (4.5 mm diameter × 6.5 mm in height). The macromer/photoinitiator/chondrocyte solutions were polymerized using ultraviolet (365 nm) light at 10 mW/cm(2) for 10 mins. Also, an articular cartilaginous ring model was used to examine the capacity of the engineered cartilage to integrate with native cartilage. Samples in the pilot study were collected at 6 weeks. Samples in the long-term experimental groups (60/40 and 70/30) were implanted into nude mice subcutaneously and harvested at 6, 12 and 18 weeks. Additionally, cylindrical constructs that were not implanted used as time zero controls. All of the harvested specimens were examined grossly and analyzed histologically and biochemically. Histologically, the neocartilage formed in the photochemically crosslinked gels resembled native articular cartilage with chondrocytes in lacunae and surrounded by new ECM. Increases in total DNA, glycosaminoglycan, and hydroxyproline were observed over the time periods studied. The neocartilage integrated with existing native cartilage. Articular cartilage generation was achieved using swine articular chondrocytes photoencapsulated in copolymer PEGDM hydrogels, and the neocartilage tissue had the ability to integrate with existing adjacent native cartilage.

Cellular automata model for human articular chondrocytes migration, proliferation and cell death: An in vitro validation.

PubMed

Vaca-González, J J; Gutiérrez, M L; Guevara, J M; Garzón-Alvarado, D A

2017-01-01

Articular cartilage is characterized by low cell density of only one cell type, chondrocytes, and has limited self-healing properties. When articular cartilage is affected by traumatic injuries, a therapeutic strategy such as autologous chondrocyte implantation is usually proposed for its treatment. This approach requires in vitro chondrocyte expansion to yield high cell number for cell transplantation. To improve the efficiency of this procedure, it is necessary to assess cell dynamics such as migration, proliferation and cell death during culture. Computational models such as cellular automata can be used to simulate cell dynamics in order to enhance the result of cell culture procedures. This methodology has been implemented for several cell types; however, an experimental validation is required for each one. For this reason, in this research a cellular automata model, based on random-walk theory, was devised in order to predict articular chondrocyte behavior in monolayer culture during cell expansion. Results demonstrated that the cellular automata model corresponded to cell dynamics and computed-accurate quantitative results. Moreover, it was possible to observe that cell dynamics depend on weighted probabilities derived from experimental data and cell behavior varies according to the cell culture period. Thus, depending on whether cells were just seeded or proliferated exponentially, culture time probabilities differed in percentages in the CA model. Furthermore, in the experimental assessment a decreased chondrocyte proliferation was observed along with increased passage number. This approach is expected to having other uses as in enhancing articular cartilage therapies based on tissue engineering and regenerative medicine.

Coordinate and synergistic effects of extensive treadmill exercise and ovariectomy on articular cartilage degeneration.

PubMed

Miyatake, Kazumasa; Muneta, Takeshi; Ojima, Miyoko; Yamada, Jun; Matsukura, Yu; Abula, Kahaer; Sekiya, Ichiro; Tsuji, Kunikazu

2016-05-31

Although osteoarthritis (OA) is a multifactorial disease, little has been reported regarding the cooperative interaction among these factors on cartilage metabolism. Here we examined the synergistic effect of ovariectomy (OVX) and excessive mechanical stress (forced running) on articular cartilage homeostasis in a mouse model resembling a human postmenopausal condition. Mice were randomly divided into four groups, I: Sham, II: OVX, III: Sham and forced running (60 km in 6 weeks), and IV: OVX and forced running. Histological and immunohistochemical analyses were performed to evaluate the degeneration of articular cartilage and synovitis in the knee joint. Morphological changes of subchondral bone were analyzed by micro-CT. Micro-CT analyses showed significant loss of metaphyseal trabecular bone volume/tissue volume (BV/TV) after OVX as described previously. Forced running increased the trabecular BV/TV in all mice. In the epiphyseal region, no visible alteration in bone morphology or osteophyte formation was observed in any of the four groups. Histological analysis revealed that OVX or forced running respectively had subtle effects on cartilage degeneration. However, the combination of OVX and forced running synergistically enhanced synovitis and articular cartilage degeneration. Although morphological changes in chondrocytes were observed during OA initiation, no signs of bone marrow edema were observed in any of the four experimental groups. We report the coordinate and synergistic effects of extensive treadmill exercise and ovariectomy on articular cartilage degeneration. Since no surgical procedure was performed on the knee joint directly in this model, this model is useful in addressing the molecular pathogenesis of naturally occurring OA.

Comparative analysis of the structure of temporomandibular joint in human and rabbit.

PubMed

Tomasello, Giovanni; Sorce, Alessandra; Mazzola, Margherita; Barone, Rosario; Lo Piccolo, Chiara; Farina, Felicia; Zummo, Giovanni; Carini, Francesco

2017-01-16

In order to increase knowledge on the morphology and structure of the articular disc of the TMJ for a better understanding of the functional role of the same, it proceeded with an investigation on histological samples in the block of 'TMJ and periarticular tissues of adult rabbits and human fetuses at different stage of development.

A Novel Method to Assess Wear Rates of Retrieved Tibial Inserts Following in-vivo Use

NASA Astrophysics Data System (ADS)

Paniogue, Tanille J.

Ultra-high molecular weight polyethylene (UHMWPE) on cobalt chrome is the bearing couple of choice for total knee arthroplasty. The number of patients undergoing total knee arthroplasty has been steadily growing and is projected to continue increasing rapidly in the near future. Many of these patients are younger and more active and therefore need a longer lasting device. However, many of these devices fail prematurely and often the primary reason for failure and ultimately revision is due to wear related issues. Therefore, examining how wear rates of the UHMWPE tibial insert change during in-vivo use can help elucidate the mechanisms of accelerated wear and hopefully aid in finding solutions to combat wear related failures. Different crosslinking treatments have been employed by manufacturers to improve wear resistance of the polyethylene. While this has been shown to be an effective way to reduce wear, crosslinking has led to other issues such as oxidative instability and a decline in mechanical properties. The purpose of this body of work is to examine how changes in oxidation, after in-vivo use, affect wear resistance. A novel testing method was developed to test the native articular surface from retrieved tibial inserts in a laboratory Pin-on-Disk (POD) simulator. The method was validated using short-duration implant articular surfaces and non-articular control pins. In the absence of high surface oxidation or severe surface damage, the articular surface pins had comparable steady state wear rates to their bulk counterparts. Tests of devices with longer in-vivo service show chemical changes consistent with a free-radical mediated oxidation mechanism. Tribological assessment of the articular surfaces shows increasing wear rates as a function of oxidation. While this relationship has been hypothesized in the literature, these experiments represent the first physical demonstration of the phenomenon. The wear mechanism is further explored through infrared spectroscopy, assessment of the wear scar, and documentation of evolution of the contact surfaces in the articulation.

Anterior Inferior Iliac Spine (AIIS) and Subspine Hip Impingement

PubMed Central

Carton, Patrick; Filan, David

2016-01-01

Summary Background Abnormal morphology of the anterior inferior iliac spine (AIIS) and the subspine region of the acetabular rim are increasingly being recognised as a source of symptomatic extra-articular hip impingement. This review article aims to highlight important differences in the pathogenesis, clinical presentation and management of extra-articular hip impingement from both the AIIS and subspine bony regions, and the outcome following surgical intervention. Methods A literature review was undertaken to examine the supporting evidence for AIIS and subspine hip impingement. A narrative account of the Author’s professional experience in this area, including operative technique for arthroscopic correction, is also presented. Results Abnormal morphology of the AIIS and subspine region has been classified using cadaveric, radiological and arthroscopic means; the clinical presentation and operative treatment has been documented in several case series studies. Dual pathology is often present - recognition and treatment of both intra- and extra-articular components are necessary for good postoperative outcome. Conclusions AIIS and sub-spine hip impingement should be considered as distinct pathological entities, which may also co-exist. Symptom relief can be expected following arthroscopic deformity correction with the treatment of concomitant intra-articular pathology. Failure to recognise and treat the extra-articular component may affect postoperative outcome. Level of evidence V. PMID:28066737

Proximal metatarsal articular surface shape and the evolution of a rigid lateral foot in hominins.

PubMed

Proctor, Daniel J

2013-12-01

This study quantifies the proximal articular surface shape of metatarsal (MT) 4 and MT 5 using three-dimensional morphometrics. Humans and apes are compared to test whether they have significantly different shapes that are skeletal correlates to comparative lateral foot function. In addition, shod and unshod humans are compared to test for significant differences in surface shape. The MT 4 fossils OH 8, Stw 628, and AL 333-160, and the MT 5 fossils AL 333-13, AL 333-78, OH 8, and Stw 114/115 are compared with humans and apes to assess whether they bear greater similarities to humans, which would imply a relatively stable lateral foot, or to apes, which would imply a flexible foot with a midfoot break. Apes have a convex curved MT 4 surface, and humans have a flat surface. The MT 4 fossils show greater similarity to unshod humans, suggesting a stable lateral foot. Unshod humans have a relatively flatter MT 4 surface compared with shod humans. There is much overlap in MT 5 shape between humans and apes, with more similarity between humans and Gorilla. The fossil MT 5 surfaces are generally flat, most similar to humans and Gorilla. Because of the high degree of shape overlap between humans and apes, one must use caution in interpreting lateral foot function from the proximal MT 5 surface alone. Copyright © 2013 Elsevier Ltd. All rights reserved.

Edible Bird’s nest extract as a chondro-protective agent for human chondrocytes isolated from osteoarthritic knee: in vitro study

PubMed Central

2013-01-01

Background Osteoarthritis (OA) is a degenerative joint disease that results in the destruction of cartilage. Edible Bird’s Nest (EBN) extract contains important components, which can reduce the progression of osteoarthritis and helps in the regeneration of the cartilage. The present study aimed to investigate the effect of EBN extract on the catabolic and anabolic activities of the human articular chondrocytes (HACs) isolated from the knee joint of patients with OA. Methods A single batch of EBN extract was prepared with hot-water extraction and coded as HMG. HACs were isolated from the knee joint cartilage removed during surgery. The optimum concentration of HMG for HAC cultures was determined using MTT assay. The effect of HMG on the catabolic and anabolic genes’ expression in HACs was measured by real-time PCR. The total amount of prostaglandin E2 (PGE2) production was determined by ELISA method, and the total sulphated glycosaminoglycan (GAGs) production was quantified by 1,9-dimethylmethylene blue (DMMB) assay. Results MTT assay showed 0.50% - 1.00% HMG supplementation promoted HACs proliferation. HMG supplementation was able to reduce the catabolic genes’ expression in cultured HACs such as matrix metalloproteinases (MMP1 & MMP3), Interleukin 1, 6 and 8 (IL-1, IL-6 & IL-8), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Prostaglandin E2 (PGE2) production was significantly reduced in HAC cultures supplemented with HMG. With regard to anabolic activity assessment, type II collagen, Aggrecan and SOX-9 gene expression as well as sGAG production was increased in the HMG supplemented groups. Conclusion Edible Bird’s Nest extract coded as HMG demonstrated chondro-protection ability on human articular chondrocytes in vitro. It reduced catabolic activities and increased cartilage extracellular matrix synthesis. It is concluded that HMG is a potential agent in the treatment of osteoarthritis. PMID:23339380

Intra-articular enzyme replacement therapy with rhIDUA is safe, well-tolerated, and reduces articular GAG storage in the canine model of mucopolysaccharidosis type I.

PubMed

Wang, Raymond Y; Aminian, Afshin; McEntee, Michael F; Kan, Shih-Hsin; Simonaro, Calogera M; Lamanna, William C; Lawrence, Roger; Ellinwood, N Matthew; Guerra, Catalina; Le, Steven Q; Dickson, Patricia I; Esko, Jeffrey D

2014-08-01

Treatment with intravenous enzyme replacement therapy and hematopoietic stem cell transplantation for mucopolysaccharidosis (MPS) type I does not address joint disease, resulting in persistent orthopedic complications and impaired quality of life. A proof-of-concept study was conducted to determine the safety, tolerability, and efficacy of intra-articular recombinant human iduronidase (IA-rhIDUA) enzyme replacement therapy in the canine MPS I model. Four MPS I dogs underwent monthly rhIDUA injections (0.58 mg/joint) into the right elbow and knee for 6 months. Contralateral elbows and knees concurrently received normal saline. No intravenous rhIDUA therapy was administered. Monthly blood counts, chemistries, anti-rhIDUA antibody titers, and synovial fluid cell counts were measured. Lysosomal storage of synoviocytes and chondrocytes, synovial macrophages and plasma cells were scored at baseline and 1 month following the final injection. All injections were well-tolerated without adverse reactions. One animal required prednisone for spinal cord compression. There were no clinically significant abnormalities in blood counts or chemistries. Circulating anti-rhIDUA antibody titers gradually increased in all dogs except the prednisone-treated dog; plasma cells, which were absent in all baseline synovial specimens, were predominantly found in synovium of rhIDUA-treated joints at study-end. Lysosomal storage in synoviocytes and chondrocytes following 6 months of IA-rhIDUA demonstrated significant reduction compared to tissues at baseline, and saline-treated tissues at study-end. Mean joint synovial GAG levels in IA-rhIDUA joints were 8.62 ± 5.86 μg/mg dry weight and 21.6 ± 10.4 μg/mg dry weight in control joints (60% reduction). Cartilage heparan sulfate was also reduced in the IA-rhIDUA joints (113 ± 39.5 ng/g wet weight) compared to saline-treated joints (142 ± 56.4 ng/g wet weight). Synovial macrophage infiltration, which was present in all joints at baseline, was abolished in rhIDUA-treated joints only. Intra-articular rhIDUA is well-tolerated and safe in the canine MPS I animal model. Qualitative and quantitative assessments indicate that IA-rhIDUA successfully reduces tissue and cellular GAG storage in synovium and articular cartilage, including cartilage deep to the articular surface, and eliminates inflammatory macrophages from synovial tissue. The MPS I canine IA-rhIDUA results suggest that clinical studies should be performed to determine if IA-rhIDUA is a viable approach to ameliorating refractory orthopedic disease in human MPS I. Copyright © 2014 Elsevier Inc. All rights reserved.

Performance of new gellan gum hydrogels combined with human articular chondrocytes for cartilage regeneration when subcutaneously implanted in nude mice.

PubMed

Oliveira, J T; Santos, T C; Martins, L; Silva, M A; Marques, A P; Castro, A G; Neves, N M; Reis, R L

2009-10-01

Gellan gum is a polysaccharide that has been recently proposed by our group for cartilage tissue-engineering applications. It is commonly used in the food and pharmaceutical industry and has the ability to form stable gels without the use of harsh reagents. Gellan gum can function as a minimally invasive injectable system, gelling inside the body in situ under physiological conditions and efficiently adapting to the defect site. In this work, gellan gum hydrogels were combined with human articular chondrocytes (hACs) and were subcutaneously implanted in nude mice for 4 weeks. The implants were collected for histological (haematoxylin and eosin and Alcian blue staining), biochemical [dimethylmethylene blue (GAG) assay], molecular (real-time PCR analyses for collagen types I, II and X, aggrecan) and immunological analyses (immunolocalization of collagen types I and II). The results showed a homogeneous cell distribution and the typical round-shaped morphology of the chondrocytes within the matrix upon implantation. Proteoglycans synthesis was detected by Alcian blue staining and a statistically significant increase of proteoglycans content was measured with the GAG assay quantified from 1 to 4 weeks of implantation. Real-time PCR analyses showed a statistically significant upregulation of collagen type II and aggrecan levels in the same periods. The immunological assays suggest deposition of collagen type II along with some collagen type I. The overall data shows that gellan gum hydrogels adequately support the growth and ECM deposition of human articular chondrocytes when implanted subcutaneously in nude mice. Copyright (c) 2009 John Wiley & Sons, Ltd.

Separate Vertical Wirings for the Extra-articular Fractures of the Distal Pole of the Patella.

PubMed

Kim, Young Mo; Yang, Jun Young; Kim, Kyung Cheon; Kang, Chan; Joo, Yong Bum; Lee, Woo Yong; Hwang, Jung Mo

2011-12-01

To evaluate the usefulness of separate vertical wirings for extra-articular fracture of distal pole of patella. We have analyzed the clinical results of 18 cases that underwent separate vertical wirings for extra-articular fracture of distal pole of the patella from March 2005 to March 2010, by using the range of motion and Bostman score. Occurrence of complication was also evaluated. Additionally, by taking simple radiographs, the correlation between the postoperative degree of anterior transposition of bone fragment and the time of bone fusion, preoperative length of bone fragment, and occurrence of comminuted fracture were investigated. It took an average of 13.8 weeks for radiological bone union after separate vertical wiring fixation. Flexion contracture was an average of 0.8 degrees and further flexion was an average of 127.6°, and Bostman score was an average of 27.5 points (excellent in 12 cases, and good in 6 cases). On the first postoperative year, average flexion contracture was 0.6 degrees and further flexion was an average of 136.3°, which exhibited increased joint motion and recovery to normal range of motion, and Bostman score was an average of 28.7 points (excellent in 16 cases, and good in 2 cases). There was no statistically significant difference between the preoperative bone fragment length and presence of comminution, and degree of anterior transposition of bone fragment after fracture union on simple radiograph (p=0.175, p=0.146). We were able to obtain satisfactory clinical results, while preserving the bone fragment by separate vertical wiring fixation for extra-articular fracture of distal pole of patella. Moreover, the method is easy to perform, which is also considered as a useful surgical method for extra-articular fracture of distal pole of patella.

Optimization of Methods for Articular Cartilage Surface Tissue Engineering: Cell Density and Transforming Growth Factor Beta Are Critical for Self-Assembly and Lubricin Secretion.

PubMed

Iwasa, Kenjiro; Reddi, A Hari

2017-07-01

Lubricin/superficial zone protein (SZP)/proteoglycan4 (PRG4) plays an important role in boundary lubrication in articular cartilage. Lubricin is secreted by superficial zone chondrocytes and synoviocytes of the synovium. The specific objective of this investigation is to optimize the methods for tissue engineering of articular cartilage surface. The aim of this study is to investigate the effect of cell density on the self-assembly of superficial zone chondrocytes and lubricin secretion as a functional assessment. Superficial zone chondrocytes were cultivated as a monolayer at low, medium, and high densities. Chondrocytes at the three different densities were treated with transforming growth factor beta (TGF-β)1 twice a week or daily, and the accumulated lubricin in the culture medium was analyzed by immunoblots and quantitated by enzyme-linked immunosorbent assay (ELISA). Cell numbers in low and medium densities were increased by TGF-β1; whereas cell numbers in high-density cell cultures were decreased by twice-a-week treatment of TGF-β1. On the other hand, the cell numbers were maintained by daily TGF-β treatment. Immunoblots and quantitation of lubricin by ELISA analysis indicated that TGF-β1 stimulated lubricin secretion by superficial zone chondrocytes at all densities with twice-a-week TGF-β treatment. It is noteworthy that the daily treatment of TGF-β1 increased lubricin much higher compared with twice-a-week treatment. These data demonstrate that daily treatment is optimal for the TGF-β1 response in a higher density of monolayer cultures. These findings have implications for self-assembly of surface zone chondrocytes of articular cartilage for application in tissue engineering of articular cartilage surface.

Intra-articular Implantation of Mesenchymal Stem Cells, Part 1

PubMed Central

Kraeutler, Matthew J.; Mitchell, Justin J.; Chahla, Jorge; McCarty, Eric C.; Pascual-Garrido, Cecilia

2017-01-01

Osteoarthritis (OA) after a partial or total meniscectomy procedure is a common pathology. Because of the high incidence of meniscectomy in the general population, as well as the significant burden of knee OA, there is increasing interest in determining methods for delaying postmeniscectomy OA. Biological therapies, including mesenchymal stem cells (MSCs), induced pluripotent stem cells (iPSCs), and platelet-rich plasma (PRP), have been proposed as possible therapies that could delay OA in this and other settings. Several studies in various animal models have evaluated the effect of injecting MSCs into the knee joints of animals with OA induced either by meniscal excision with or without anterior cruciate ligament transection. When compared with control groups receiving injections without progenitor cells, short-term benefits in the experimental groups have been reported. In human subjects, there are limited data to determine the effect of biological therapies for use in delaying or preventing the onset of OA after a meniscectomy procedure. The purpose of this review is to highlight the findings in the presently available literature on the use of intra-articular implantation of MSCs postmeniscectomy and to offer suggestions for future research with the goal of delaying or treating early OA postmeniscectomy with MSCs. PMID:28203597

Optimization of a chondrogenic medium through the use of factorial design of experiments.

PubMed

Enochson, Lars; Brittberg, Mats; Lindahl, Anders

2012-12-01

The standard culture system for in vitro cartilage research is based on cells in a three-dimensional micromass culture and a defined medium containing the chondrogenic key growth factor, transforming growth factor (TGF)-β1. The aim of this study was to optimize the medium for chondrocyte micromass culture. Human chondrocytes were cultured in different media formulations, designed with a factorial design of experiments (DoE) approach and based on the standard medium for redifferentiation. The significant factors for the redifferentiation of the chondrocytes were determined and optimized in a two-step process through the use of response surface methodology. TGF-β1, dexamethasone, and glucose were significant factors for differentiating the chondrocytes. Compared to the standard medium, TGF-β1 was increased 30%, dexamethasone reduced 50%, and glucose increased 22%. The potency of the optimized medium was validated in a comparative study against the standard medium. The optimized medium resulted in micromass cultures with increased expression of genes important for the articular chondrocyte phenotype and in cultures with increased glycosaminoglycan/DNA content. Optimizing the standard medium with the efficient DoE method, a new medium that gave better redifferentiation for articular chondrocytes was determined.

ASB Clinical Biomechanics Award Paper 2010: Virtual Pre-Operative Reconstruction Planning for Comminuted Articular Fractures

PubMed Central

Thomas, Thaddeus P.; Anderson, Donald D.; Willis, Andrew R.; Liu, Pengcheng; Marsh, J. Lawrence; Brown, Thomas D.

2010-01-01

Background Highly comminuted intra-articular fractures are complex and difficult injuries to treat. Once emergent care is rendered, the definitive treatment objective is to restore the original anatomy while minimizing surgically induced trauma. Operations that use limited or percutaneous approaches help preserve tissue vitality, but reduced visibility makes reconstruction more difficult. A pre-operative plan of how comminuted fragments would best be re-positioned to restore anatomy helps in executing a successful reduction. Methods In this study, methods for virtually reconstructing a tibial plafond fracture were developed and applied to clinical cases. Building upon previous benchtop work, novel image analysis techniques and puzzle solving algorithms were developed for clinical application. Specialty image analysis tools were used to segment the fracture fragment geometries from CT data. The original anatomy was then restored by matching fragment native (periosteal and subchondral) bone surfaces to an intact template, generated from the uninjured contralateral limb. Findings Virtual reconstructions obtained for ten tibial plafond fracture cases had average alignment errors of 0.39 (0.5 standard deviation) mm. In addition to precise reduction planning, 3D puzzle solutions can help identify articular deformities and bone loss. Interpretation The results from this study indicate that 3D puzzle solving provides a powerful new tool for planning the surgical reconstruction of comminuted articular fractures. PMID:21215501

Treatment of Displaced Intra-articular Calcaneal Fractures by Intramedullary Nail. Preliminary Report.

PubMed

Falis, Mirosław; Pyszel, Krystian

2016-03-23

Open reduction and plate stabilisation is a recognised method of treatment of intra-articular calcaneal fractures. The surgical approach to the calcaneal bone used in these procedures is associated with a high risk of complications. The aim of this paper is to present the author's experience with a new surgical method and analyse early outcomes of the treatment of calcaneal fractures by Calcanail intramedullary nailing. The study encompassed 17 patients (5 women and 12 men) with 18 calcaneal fractures (5 in the right foot and 13 in the left foot). The mean age of the patients was 47 years (range: 22-68 years). The mean time between the injury and surgery was 6 days (range: 3-14 days). The mean duration of follow-up was 12 months (range: 6-18 months). The fractures were classified according to the system presented by Guy Utheza. Bone union was achieved in all patients within 12 weeks of surgery. No infectious complications were observed. The mean AOFAS score was 82/100. Mean Bohler's angle was -3 degrees pre-operatively and +29 degrees post-operatively. 1. The use of Calcanail intramedullary nailing in the treatment of displaced intra-articular fractures is a minimally invasive procedure associated with a low risk of complications. 2. The innovative posterior approach allows for the intrafocal reduction of an articular surface fracture through the prepared intramedullary canal.

Bi-articular Knee-Ankle-Foot Exoskeleton Produces Higher Metabolic Cost Reduction than Weight-Matched Mono-articular Exoskeleton.

PubMed

Malcolm, Philippe; Galle, Samuel; Derave, Wim; De Clercq, Dirk

2018-01-01

The bi-articular m. gastrocnemius and the mono-articular m. soleus have different and complementary functions during walking. Several groups are starting to use these biological functions as inspiration to design prostheses with bi-articular actuation components to replace the function of the m. gastrocnemius. Simulation studies indicate that a bi-articular configuration and spring that mimic the m. gastrocnemius could be beneficial for orthoses or exoskeletons. Our aim was to test the effect of a bi-articular and spring configuration that mimics the m. gastrocnemius and compare this to a no-spring and mono-articular configuration. We tested nine participants during walking with knee-ankle-foot exoskeletons with dorsally mounted pneumatic muscle actuators. In the bi-articular plus spring condition the pneumatic muscles were attached to the thigh segment with an elastic cord. In the bi-articular no-spring condition the pneumatic muscles were also attached to the thigh segment but with a non-elastic cord. In the mono-articular condition the pneumatic muscles were attached to the shank segment. We found the highest reduction in metabolic cost of 13% compared to walking with the exoskeleton powered-off in the bi-articular plus spring condition . Possible explanations for this could be that the exoskeleton delivered the highest total positive work in this condition at the ankle and the knee and provided more assistance during the isometric phase of the biological plantarflexors. As expected we found that the bi-articular conditions reduced m. gastrocnemius EMG more than the mono-articular condition but this difference was not significant. We did not find that the mono-articular condition reduces the m. soleus EMG more than the bi-articular conditions . Knowledge of specific effects of different exoskeleton configurations on metabolic cost and muscle activation could be useful for providing customized assistance for specific gait impairments.

Bi-articular Knee-Ankle-Foot Exoskeleton Produces Higher Metabolic Cost Reduction than Weight-Matched Mono-articular Exoskeleton

PubMed Central

Malcolm, Philippe; Galle, Samuel; Derave, Wim; De Clercq, Dirk

2018-01-01

The bi-articular m. gastrocnemius and the mono-articular m. soleus have different and complementary functions during walking. Several groups are starting to use these biological functions as inspiration to design prostheses with bi-articular actuation components to replace the function of the m. gastrocnemius. Simulation studies indicate that a bi-articular configuration and spring that mimic the m. gastrocnemius could be beneficial for orthoses or exoskeletons. Our aim was to test the effect of a bi-articular and spring configuration that mimics the m. gastrocnemius and compare this to a no-spring and mono-articular configuration. We tested nine participants during walking with knee-ankle-foot exoskeletons with dorsally mounted pneumatic muscle actuators. In the bi-articular plus spring condition the pneumatic muscles were attached to the thigh segment with an elastic cord. In the bi-articular no-spring condition the pneumatic muscles were also attached to the thigh segment but with a non-elastic cord. In the mono-articular condition the pneumatic muscles were attached to the shank segment. We found the highest reduction in metabolic cost of 13% compared to walking with the exoskeleton powered-off in the bi-articular plus spring condition. Possible explanations for this could be that the exoskeleton delivered the highest total positive work in this condition at the ankle and the knee and provided more assistance during the isometric phase of the biological plantarflexors. As expected we found that the bi-articular conditions reduced m. gastrocnemius EMG more than the mono-articular condition but this difference was not significant. We did not find that the mono-articular condition reduces the m. soleus EMG more than the bi-articular conditions. Knowledge of specific effects of different exoskeleton configurations on metabolic cost and muscle activation could be useful for providing customized assistance for specific gait impairments. PMID:29551959

A review of extra-articular prosthetic stabilization of the cranial cruciate ligament-deficient stifle.

PubMed

Tonks, C A; Lewis, D D; Pozzi, A

2011-01-01

Extra-articular prosthetic stabilization techniques have been used as a method of stabilization of the cranial cruciate ligament (CrCL)-deficient stifle for decades. During extra-articular prosthetic stabilization, the prosthesis is anchored to the femur and tibia, and tensioned in the attempt to resolve femorotibial instability. The position of the anchor points of the prosthesis is crucial for restoring a normal range of joint motion and mitigating alterations in prosthesis tension during motion. Recently developed techniques offer several innovations with potential advantages such as bone-to-bone fixation, prosthetic materials with better mechanical properties, and improved isometry of the anchor points. Whether these innovations provide clinically superior results to the traditional techniques such as lateral circumfabellar-tibial suture techniques has yet to be determined.

Optical characterization of porcine articular cartilage using a polarimetry technique with differential Mueller matrix formulism.

PubMed

Chang, Ching-Min; Lo, Yu-Lung; Tran, Nghia-Khanh; Chang, Yu-Jen

2018-03-20

A method is proposed for characterizing the optical properties of articular cartilage sliced from a pig's thighbone using a Stokes-Mueller polarimetry technique. The principal axis angle, phase retardance, optical rotation angle, circular diattenuation, diattenuation axis angle, linear diattenuation, and depolarization index properties of the cartilage sample are all decoupled in the proposed analytical model. Consequently, the accuracy and robustness of the extracted results are improved. The glucose concentration, collagen distribution, and scattering properties of samples from various depths of the articular cartilage are systematically explored via an inspection of the related parameters. The results show that the glucose concentration and scattering effect are both enhanced in the superficial region of the cartilage. By contrast, the collagen density increases with an increasing sample depth.

Mechanical Testing of Hydrogels in Cartilage Tissue Engineering: Beyond the Compressive Modulus

PubMed Central

Xiao, Yinghua; Friis, Elizabeth A.; Gehrke, Stevin H.

2013-01-01

Injuries to articular cartilage result in significant pain to patients and high medical costs. Unfortunately, cartilage repair strategies have been notoriously unreliable and/or complex. Biomaterial-based tissue-engineering strategies offer great promise, including the use of hydrogels to regenerate articular cartilage. Mechanical integrity is arguably the most important functional outcome of engineered cartilage, although mechanical testing of hydrogel-based constructs to date has focused primarily on deformation rather than failure properties. In addition to deformation testing, as the field of cartilage tissue engineering matures, this community will benefit from the addition of mechanical failure testing to outcome analyses, given the crucial clinical importance of the success of engineered constructs. However, there is a tremendous disparity in the methods used to evaluate mechanical failure of hydrogels and articular cartilage. In an effort to bridge the gap in mechanical testing methods of articular cartilage and hydrogels in cartilage regeneration, this review classifies the different toughness measurements for each. The urgency for identifying the common ground between these two disparate fields is high, as mechanical failure is ready to stand alongside stiffness as a functional design requirement. In comparing toughness measurement methods between hydrogels and cartilage, we recommend that the best option for evaluating mechanical failure of hydrogel-based constructs for cartilage tissue engineering may be tensile testing based on the single edge notch test, in part because specimen preparation is more straightforward and a related American Society for Testing and Materials (ASTM) standard can be adopted in a fracture mechanics context. PMID:23448091

Sonographically guided posteromedial approach for intra-articular knee injections: a safe, accurate, and efficient method.

PubMed

Tresley, Jonathan; Jose, Jean

2015-04-01

Osteoarthritis of the knee can be a debilitating and extremely painful condition. In patients who desire to postpone knee arthroplasty or in those who are not surgical candidates, percutaneous knee injection therapies have the potential to reduce pain and swelling, maintain joint mobility, and minimize disability. Published studies cite poor accuracy of intra-articular knee joint injections without imaging guidance. We present a sonographically guided posteromedial approach to intra-articular knee joint injections with 100% accuracy and no complications in a consecutive series of 67 patients undergoing subsequent computed tomographic or magnetic resonance arthrography. Although many other standard approaches are available, a posteromedial intra-articular technique is particularly useful in patients with a large body habitus and theoretically allows for simultaneous aspiration of Baker cysts with a single sterile preparation and without changing the patient's position. The posteromedial technique described in this paper is not compared or deemed superior to other standard approaches but, rather, is presented as a potentially safe and efficient alternative. © 2015 by the American Institute of Ultrasound in Medicine.

Articular cartilage endurance and resistance to osteoarthritic changes require transcription factor Erg.

PubMed

Ohta, Yoichi; Okabe, Takahiro; Larmour, Colleen; Di Rocco, Agnese; Maijenburg, Marijke W; Phillips, Amanda; Speck, Nancy A; Wakitani, Shigeyuki; Nakamura, Takashi; Yamada, Yoshihiko; Enomoto-Iwamoto, Motomi; Pacifici, Maurizio; Iwamoto, Masahiro

2015-10-01

To determine whether and how the transcription factor Erg participates in the genesis, establishment, and maintenance of articular cartilage. Floxed Erg mice were mated with Gdf5-Cre mice to generate conditional mutants lacking Erg in their joints. Joints of mutant and control mice were subjected to morphologic and molecular characterization and also to experimental surgically induced osteoarthritis (OA). Gene expression, promoter reporter assays, and gain- and loss-of-function in vitro tests were used to characterize molecular mechanisms of Erg action. Conditional Erg ablation did not elicit obvious changes in limb joint development and overall phenotype in juvenile mice. However, as mice aged, joints of mutant mice degenerated spontaneously and exhibited clear OA-like phenotypic defects. Joints in juvenile mutant mice were more sensitive to surgically induced OA and became defective sooner than operated joints in control mice. Global gene expression data and other studies identified parathyroid hormone-related protein (PTHrP) and lubricin as possible downstream effectors and mediators of Erg action in articular chondrocytes. Reporter assays using control and mutated promoter-enhancer constructs indicated that Erg acted on Ets DNA binding sites to stimulate PTHrP expression. Erg was up-regulated in severely affected areas in human OA articular cartilage but remained barely appreciable in areas of less affected cartilage. The study shows for the first time that Erg is a critical molecular regulator of the endurance of articular cartilage during postnatal life and that Erg can mitigate spontaneous and experimental OA. Erg appears to do this through regulating expression of PTHrP and lubricin, factors known for their protective roles in joints. © 2015, American College of Rheumatology.

Distribution of Endo180 receptor and ligand in developing articular cartilage.

PubMed

Howard, M J; Chambers, M G; Mason, R M; Isacke, C M

2004-01-01

To investigate the expression of a novel member of the mannose receptor family, Endo180 (also known as uPARAP), and the distribution of Endo180 ligand(s) in the articular cartilage and growth plate of normal CBA mice and STR/ort mice, a well characterized model of spontaneous osteoarthritis. A polyclonal anti-Endo180 antibody was used to determine receptor expression. The Endo180 extracellular domain fused to a human immunoglobulin Fc tail was used to detect ligand. Endo180 receptor was strongly expressed in chondrocytes both in vitro and throughout the articular cartilage of young CBA and STR/ort mice. Expression decreased in older animals. In STR/ort mice with osteoarthritic lesions, no upregulation of Endo180 was detected. In the developing growth plate, Endo180 was expressed strongly by the proliferating chondrocytes. In contrast, Endo180 ligand was detected most strongly in hypertrophic zone of the growth plate and only at low levels in articular cartilage. In cultured chondrocytes, Endo180 was localized on the cell surface and in intracellular vesicles. Constitutively recycling endocytic receptors function to internalize ligand from the extracellular milieu and the ability of Endo180 to bind both glycosylated ligands and collagens suggests a role in extracellular matrix remodeling. Expression of Endo180 in articular cartilage chondrocytes of young, but not old, mice and the reciprocal expression of Endo180 and its ligands in the growth plate suggest that this receptor is involved in cartilage development but not in cartilage homeostasis. In addition, our data indicates that Endo180 does not appear to play a role in the development or progression of murine osteoarthritis.

Osteoarthritis-derived chondrocytes are a potential source of multipotent progenitor cells for cartilage tissue engineering

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oda, Tomoyuki; Sakai, Tadahiro; Hiraiwa, Hideki

The natural healing capacity of damaged articular cartilage is poor, rendering joint surface injuries a prime target for regenerative medicine. While autologous chondrocyte or mesenchymal stem cell (MSC) implantation can be applied to repair cartilage defects in young patients, no appropriate long-lasting treatment alternative is available for elderly patients with osteoarthritis (OA). Multipotent progenitor cells are reported to present in adult human articular cartilage, with a preponderance in OA cartilage. These facts led us to hypothesize the possible use of osteoarthritis-derived chondrocytes as a cell source for cartilage tissue engineering. We therefore analyzed chondrocyte- and stem cell-related markers, cell growthmore » rate, and multipotency in OA chondrocytes (OACs) and bone marrow-derived MSCs, along with normal articular chondrocytes (ACs) as a control. OACs demonstrated similar phenotype and proliferation rate to MSCs. Furthermore, OACs exhibited multilineage differentiation ability with a greater chondrogenic differentiation ability than MSCs, which was equivalent to ACs. We conclude that chondrogenic capacity is not significantly affected by OA, and OACs could be a potential source of multipotent progenitor cells for cartilage tissue engineering. - Highlights: • Osteoarthritis chondrocytes (OACs) have multilineage differentiation capacity. • Articular chondrocytes (ACs) and OACs have similar gene expression profiles. • OACs have high chondrogenic potential. • OACs could be a cell resource for cartilage tissue engineering.« less

Osteoarthritic human chondrocytes proliferate in 3D co-culture with mesenchymal stem cells in suspension bioreactors.

PubMed

Khurshid, Madiha; Mulet-Sierra, Aillette; Adesida, Adetola; Sen, Arindom

2018-03-01

Osteoarthritis (OA) is a painful disease, characterized by progressive surface erosion of articular cartilage. The use of human articular chondrocytes (hACs) sourced from OA patients has been proposed as a potential therapy for cartilage repair, but this approach is limited by the lack of scalable methods to produce clinically relevant quantities of cartilage-generating cells. Previous studies in static culture have shown that hACs co-cultured with human mesenchymal stem cells (hMSCs) as 3D pellets can upregulate proliferation and generate neocartilage with enhanced functional matrix formation relative to that produced from either cell type alone. However, because static culture flasks are not readily amenable to scale up, scalable suspension bioreactors were investigated to determine if they could support the co-culture of hMSCs and OA hACs under serum-free conditions to facilitate clinical translation of this approach. When hACs and hMSCs (1:3 ratio) were inoculated at 20,000 cells/ml into 125-ml suspension bioreactors and fed weekly, they spontaneously formed 3D aggregates and proliferated, resulting in a 4.75-fold increase over 16 days. Whereas the apparent growth rate was lower than that achieved during co-culture as a 2D monolayer in static culture flasks, bioreactor co-culture as 3D aggregates resulted in a significantly lower collagen I to II mRNA expression ratio and more than double the glycosaminoglycan/DNA content (5.8 vs. 2.5 μg/μg). The proliferation of hMSCs and hACs as 3D aggregates in serum-free suspension culture demonstrates that scalable bioreactors represent an accessible platform capable of supporting the generation of clinical quantities of cells for use in cell-based cartilage repair. Copyright © 2017 John Wiley & Sons, Ltd.

Hyaluronan suppresses lidocaine-induced apoptosis of human chondrocytes in vitro by inhibiting the p53-dependent mitochondrial apoptotic pathway

PubMed Central

Lee, Yoon-Jin; Kim, Soo A; Lee, Sang-Han

2016-01-01

Aim: Intra-articular injection of local anesthetics (LAs) is a common procedure for therapeutic purposes. However, LAs have been found toxic to articular cartilage, and hyaluronan may attenuate this toxicity. In this study we investigated whether hyaluronan attenuated lidocaine-induced chondrotoxicity, and if so, to elucidate the underlying mechanisms. Methods: Human chondrocyte cell line SW1353 and newly isolated murine chondrocytes were incubated in culture medium containing hyaluronan and/or lidocaine for 72 h. Cell viability was evaluated using MTT assay. Cell apoptosis was detected with DAPI staining, caspase 3/7 activity assay and flow cytometry. Cell cycle distributions, ROS levels and mitochondrial membrane potential (ΔΨm) were determined using flow cytometry. The expression of p53 and p53-regulated gene products was measured with Western blotting. Results: Lidocaine (0.005%−0.03%) dose-dependently decreased the viability of SW1353 cells. This local anesthetic (0.015%, 0.025%) induced apoptosis, G2/M phase arrest and loss of ΔΨm, and markedly increased ROS production in SW1353 cells. Hyaluronan (50−800 μg/mL) alone did not affect the cell viability, but co-treatment with hyaluronan (200 μg/mL) significantly attenuated lidocaine-induced apoptosis and other abnormalities in SW1353 cells. Furthermore, co-treatment with lidocaine and hyaluronan significantly decreased the levels of p53 and its transcription targets Bax and p21 in SW1353 cells, although treatment with lidocaine alone did not significantly change these proteins. Similar results were obtained in ex vivo cultured murine chondrocytes. Conclusion: Hyaluronan suppresses lidocaine-induced apoptosis of human chondrocytes in vitro through inhibiting the p53-dependent mitochondrial apoptotic pathway. PMID:27041463

Treatment of subtalar calcanean fractures using trans-osseous limited lateral approach.

PubMed

Ragab, Abdelaleem H; Mubark, Islam M; Nagi, Ahmed M; Abdelnaby, Mohamed Aly

2014-01-01

Calcaneal fractures are the most common fractures of the tarsal bones. The majority of these fractures are produced by axial force like a fall from a height. Controversy still exists on the best line of treatment. This study is to evaluate the results of trans-osseous limited lateral approach as a minimally invasive surgical treatment of the displaced intra-articular calcaneal fractures. The study included forty two patients (46 feet) with displaced intra-articular calcaneal fractures admitted to El-Hadra University Hospital. They were treated by trans-osseous open reduction of subtalar joint and internal fixation by k-wires consuming the trans-osseous limited lateral approach. Out of 42 patients, 36 pateints (85.7%) were males. Using calcaneal fracture scoring system, the mean score was 67.55+17.35. Satisfactory results were found in 26 patients (61.9%), while 16 patients (38.1%) had unsatisfactory results. There was significant relationship between classification of the fracture and the final results (the more the grade of the fracture, the worse the final score) (x 2 =5.914, p=0.05). The value of calcaneal angles were significantly improved after surgery including bohler angle (p=0.0001), gissane angle (p=0.0001), calcaneal pitch angle (p=0.001) and calcaneofibular space (p=0.0021). 1. Trans-osseous limited lateral approach is an effective method for management of intra articular calcaneal fractures. 2. Anatomical reduction for intra articular calcaneal fractures is essential. 3. Functional outcome of intra articular calcaneal fractures depends upon the initial damage of the articular cartilage. 4. There is a need for multi-center prospective randomized study for accurate assessment of the results of operative management of intra articular calcaneal fractures involving pre and post-operative CT for assessment of reduction and using a rational scoring system and a long period of follow up.

Locking Compression Plate in Distal Femoral Intra-Articular Fractures: Our Experience

PubMed Central

Kiran Kumar, G. N.; Sharma, Gaurav; Farooque, Kamran; Sharma, Vijay; Ratan, Ratnav; Yadav, Sanjay; Lakhotia, Devendra

2014-01-01

Background. Intra-articular fractures of distal femur present a huge surgical challenge. The aim of this study is to evaluate functional outcome, fracture healing, and the complications of distal femoral intra-articular fractures using locking compression plates. Material and Methods. We reviewed 46 distal femoral fractures treated with distal femoral locking compression plates between 2009 to 2012. There were 36 men and 10 women with mean age of 35 years (range 20–72). More than half of the patients were of type C3 (AO classification) and had been caused by high energy trauma with associated injuries. Results. 2 patients were lost to follow-up. Of the remaining 44 patients, the mean follow-up period was 25 months (range 18–36). The mean time for radiological union was 12 weeks (range 10–18) except 2 patients which had gone for nonunion. At the latest follow up ROM >120° is noted in 32 patients, 90–120 in 10 patients, and 70–90 in 2 patients. 38 patients (86%) had good/excellent outcome. Conclusion. Use of standard lateral approach for simple intra-articular distal femoral fractures (C1) and transarticular/minimally invasive techniques for complex intra-articular fractures (C2/C3) results in improved exposure of the knee joint and better union rates with low incidence of bone grafting. PMID:27355064

Partial articular-sided rotator cuff tears: in situ repair versus tear completion prior to repair.

PubMed

Sethi, Paul M; Rajaram, Arun; Obopilwe, Elifho; Mazzocca, Augustus D

2013-06-01

Uncertainty exists over the ideal surgical treatment method for partial articular-sided rotator cuff tears, with options ranging from debridement to in situ repair to tear completion prior to repair. The purpose of this study was to determine whether in situ repair was a viable biomechanical treatment option compared with tear completion prior to repair of partial articular-sided rotator cuff tears. Fourteen fresh-frozen cadaveric shoulders were dissected. Partial articular-sided tears were created and repaired using in situ repair or tear completion prior to the repair. Strain and displacement were measured at 45°, 60°, and 90° of glenohumeral abduction. Testing was performed with a load of 100 N applied for 30 cycles. Data from the biomechanical testing displayed 4 conditions that showed improved characteristics of in situ repair over completion and repair: bursal-sided strain anteriorly at 45°, bursal-sided strain anteriorly at 90°, bursal-sided displacement anteriorly at 45°, and bursal-sided displacement anteriorly at 90°. The data indicate that in situ repair is a viable biomechanical treatment option compared with tear completion prior to repair of partial articular-sided rotator cuff tears. When clinically appropriate, the in situ repair may offer some biomechanical advantages, with lower strain and displacement observed on the bursal side compared with tear completion prior to repair. Copyright 2013, SLACK Incorporated.

Gene Expression in Human Meniscal Tears has Limited Association with Early Degenerative Changes in Knee Articular Cartilage

PubMed Central

Brophy, Robert H.; Sandell, Linda J.; Cheverud, James M.; Rai, Muhammad Farooq

2018-01-01

Purpose/Aim Meniscus tears are a common injury to the knee associated with the development of osteoarthritis. Gene expression in the injured meniscus may be associated with early degeneration in the articular cartilage. The purpose of this study was to test the hypothesis that gene expression in meniscus tears is associated with early degenerative changes in the articular cartilage at the time of partial meniscectomy. Materials and Methods Torn meniscus was removed at the time of partial meniscectomy in 63 patients without radiographic osteoarthritis. Meniscal mRNA expression was measured by quantitative PCR for multiple molecular markers of osteoarthritis and cartilage homeostasis. The presence of early degenerative changes in the knee was recorded by X-ray (N=63), magnetic resonance imaging (MRI, N=48) and arthroscopy (N=63). Gene expression was tested for correlation with the presence/absence of degenerative changes after adjusting for age, sex and body mass index. Results Overall gene expression varied significantly with degenerative changes based on X-ray (P=0.047) and MRI (P=0.018). The linear combination of gene variation was also significant. However, only adiponectin (ADIPOQ) (P=0.015) was expressed at a significantly lower level in patients with chondrosis on MRI while the expression of ADIPOQ (P=0.035) and resistin (RETN) (P=0.017) was higher in patients with early degenerative changes on X-ray. Conclusions There is an overall association of gene expression in meniscal tears to early degenerative changes in the knee, but only a limited number of specific genes demonstrate this relationship. The roles of adiponectin and resistin in knee injury and osteoarthritis deserve further study. PMID:27435997

Evaluation of degenerative changes in articular cartilage of osteoarthritis by Raman spectroscopy

NASA Astrophysics Data System (ADS)

Oshima, Yusuke; Ishimaru, Yasumitsu; Kiyomatsu, Hiroshi; Hino, Kazunori; Miura, Hiromasa

2018-02-01

Osteoarthritis (OA) is a very common joint disease in the aging population. Main symptom of OA is accompanied by degenerative changes of articular cartilage. Cartilage contains mostly type II collagen and proteoglycans, so it is difficult to access the quality and morphology of cartilage tissue in situ by conventional diagnostic tools (X-ray, MRI and echography) directly or indirectly. Raman spectroscopy is a label-free technique which enables to analyze molecular composition in degenerative cartilage. In this proposal, we aim to develop Raman spectroscopic system for the quality assessment of articular cartilage during arthroscopic surgery. Toward this goal, we are focusing on the proteoglycan content and collagen fiber alignment in cartilage matrix which may be associated with degenerative changes in OA, and we designed an original Raman device for remote sensing during arthroscopic surgery. In this project, we define the grading system for cartilage defect based on Raman spectroscopy, and we complete the evaluation of the Raman probing system which makes it possible to detect early stage of degenerative cartilage as a novel tool for OA diagnosis using human subject.

Development of body weight support gait training system using antagonistic bi-articular muscle model.

PubMed

Shibata, Yoshiyuki; Imai, Shingo; Nobutomo, Tatsuya; Miyoshi, Tasuku; Yamamoto, Shin-Ichiroh

2010-01-01

The purpose of this study is to develop a body weight support gait training system for stroke and spinal cord injury. This system consists of a powered orthosis, treadmill and equipment of body weight support. Attachment of the powered orthosis is able to fit subject who has difference of body size. This powered orthosis is driven by pneumatic McKibben actuator. Actuators are arranged as pair of antagonistic bi-articular muscle model and two pairs of antagonistic mono-articular muscle model like human musculoskeletal system. Part of the equipment of body weight support suspend subject by wire harness, and body weight of subject is supported continuously by counter weight. The powered orthosis is attached equipment of body weight support by parallel linkage, and movement of the powered orthosis is limited at sagittal plane. Weight of the powered orthosis is compensated by parallel linkage with gas-spring. In this study, we developed system that has orthosis powered by pneumatic McKibben actuators and equipment of body weight support. We report detail of our developed body weight support gait training system.

PRP and Articular Cartilage: A Clinical Update

PubMed Central

Rossi, Roberto; Castoldi, Filippo; Michielon, Gianni

2015-01-01

The convincing background of the recent studies, investigating the different potentials of platelet-rich plasma, offers the clinician an appealing alternative for the treatment of cartilage lesions and osteoarthritis. Recent evidences in literature have shown that PRP may be helpful both as an adjuvant for surgical treatment of cartilage defects and as a therapeutic tool by intra-articular injection in patients affected by osteoarthritis. In this review, the authors introduce the trophic and anti-inflammatory properties of PRP and the different products of the available platelet concentrates. Then, in a complex scenario made of a great number of clinical variables, they resume the current literature on the PRP applications in cartilage surgery as well as the use of intra-articular PRP injections for the conservative treatment of cartilage degenerative lesions and osteoarthritis in humans, available as both case series and comparative studies. The result of this review confirms the fascinating biological role of PRP, although many aspects yet remain to be clarified and the use of PRP in a clinical setting has to be considered still exploratory. PMID:26075244

Sulforaphane represses matrix-degrading proteases and protects cartilage from destruction in vitro and in vivo.

PubMed

Davidson, Rose K; Jupp, Orla; de Ferrars, Rachel; Kay, Colin D; Culley, Kirsty L; Norton, Rosemary; Driscoll, Clare; Vincent, Tonia L; Donell, Simon T; Bao, Yongping; Clark, Ian M

2013-12-01

Sulforaphane (SFN) has been reported to regulate signaling pathways relevant to chronic diseases. The aim of this study was to investigate the impact of SFN treatment on signaling pathways in chondrocytes and to determine whether sulforaphane could block cartilage destruction in osteoarthritis. Gene expression, histone acetylation, and signaling of the transcription factors NF-E2-related factor 2 (Nrf2) and NF-κB were examined in vitro. The bovine nasal cartilage explant model and the destabilization of the medial meniscus (DMM) model of osteoarthritis in the mouse were used to assess chondroprotection at the tissue and whole-animal levels. SFN inhibited cytokine-induced metalloproteinase expression in primary human articular chondrocytes and in fibroblast-like synovial cells. SFN acted independently of Nrf2 and histone deacetylase activity to regulate metalloproteinase expression in human articular chondrocytes but did mediate prolonged activation of JNK and p38 MAPK. SFN attenuated NF-κB signaling at least through inhibition of DNA binding in human articular chondrocytes, with decreased expression of several NF-κB-dependent genes. Compared with cytokines alone, SFN (10 μM) abrogated cytokine-induced destruction of bovine nasal cartilage at both the proteoglycan and collagen breakdown levels. An SFN-rich diet (3 μmoles/day SFN versus control chow) decreased the arthritis score in the DMM model of osteoarthritis in the mouse, with a concurrent block of early DMM-induced gene expression changes. SFN inhibits the expression of key metalloproteinases implicated in osteoarthritis, independently of Nrf2, and blocks inflammation at the level of NF-κB to protect against cartilage destruction in vitro and in vivo. © The Authors. Arthritis & Rheumatism is published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology.

Improvement of arthroscopic cartilage stiffness probe using amorphous diamond coating.

PubMed

Töyräs, Juha; Korhonen, Rami K; Voutilainen, Tanja; Jurvelin, Jukka S; Lappalainen, Reijo

2005-04-01

During arthroscopic evaluation of articular cartilage unstable contact and even slipping of the measurement instrument on the tissue surface may degrade the reproducibility of the measurement. The main aim of the present study was to achieve more stable contact by controlling the friction between articular cartilage surface and the arthroscopic cartilage stiffness probe (Artscan 200, Artscan Oy, Helsinki, Finland) using amorphous diamond (AD) coating. In order to obtain surfaces with different average roughnesses (R(a)), polished stainless steel disks were coated with AD by using the filtered pulsed arc-discharge (FPAD) method. Dynamic coefficient of friction (mu) between the articular cartilage (n = 8) and the coated plates along one non-coated plate was then determined. The friction between AD and cartilage could be controlled over a wide range (mu = 0.027-0.728, p < 0.05, Wilcoxon test) by altering the roughness. Possible deterioration of cartilage was investigated by measuring surface roughness after friction tests and comparing it with the roughness of the adjacent, untested samples (n = 8). Importantly, even testing with the roughest AD (R(a) = 1250 nm) did not damage articular surface. On the basis of the friction measurements, a proper AD coating was selected for the stiffness probe. The performance of coated and non-coated probe was compared by measuring bovine osteochondral samples (n = 22) with both instruments. The reproducibility of the stiffness measurements was significantly better with the AD-coated probe (CV% = 4.7) than with the uncoated probe (CV% = 8.2). To conclude, AD coating can be used to safely control dynamic friction with articular surface. Sufficient friction between articular surface and reference plate of the arthroscopic probe improves significantly reproducibility of the stiffness measurements. (c) 2005 Wiley Periodicals, Inc.

Extension of knee immobilization delays recovery of histological damages in the anterior cruciate ligament insertion and articular cartilage in rabbits.

PubMed

Mutsuzaki, Hirotaka; Nakajima, Hiromi; Sakane, Masataka

2018-01-01

[Purpose] To investigate the influence of knee immobilization period on recovery of histological damages in the anterior cruciate ligament (ACL) insertion and articular cartilage in rabbits. This knowledge is important for determining the appropriate rehabilitation approach for patients with ligament injuries, fracture, disuse atrophy, and degenerative joint disease. [Materials and Methods] Forty-eight male Japanese white rabbits were divided equally into the remobilization and control groups. The remobilization group had the right knee surgically immobilized, and was divided equally into four subgroups according to the duration of immobilization (1, 2, 4 and 8 weeks). After the immobilization was removed, the rabbits moved freely for 8 weeks. The control group underwent sham operation and followed the same time course as the remobilization group. The chondrocyte apoptosis rate and chondrocyte proliferation rate in the ACL insertion and articular cartilage were analyzed after remobilization. [Results] In the ACL insertion, the remobilization group had a higher chondrocyte apoptosis rate than the control group after 8 weeks of immobilization, and a lower chondrocyte proliferation rate than the control group after 4 and 8 weeks of immobilization. In the articular cartilage, the remobilization group had a lower chondrocyte proliferation rate than the control group after 8 weeks of immobilization. After 8 weeks of remobilization, the ACL insertion and articular cartilage are not completely recovered after 4 and 8 weeks of immobilization, respectively. [Conclusion] Our results suggest that 8 weeks of remobilization will result in recovery of the ACL insertion after 2 weeks of knee immobilization, and recovery of the articular cartilage after 4 weeks of knee immobilization. If 8 weeks of immobilization occurs, a remobilization duration of more than 8 weeks may be necessary.

[Osteosynthesis of distal radius fractures by by flexible intramedullary nailing (Geneva experience)].

PubMed

Flisch, C W; Della Santa, D R

1998-01-01

In 1949 Leslie Rush described a new method of management of Colles' fractures by means of a rigid medullary nail. Claude Py in 1969 followed this concept but used two flexible intramedullary pins. After briefly recalling the biomechanical principle and operating technique, the authors outline their series of 39 extra- and intra-articular fractures (10 males and 29 females) operated between March 1995 and April 1996 with an average follow-up of 6.5 months (1.5-14.5 months). The radiological and functional results are discussed: 55% of the cases showed good anatomical reduction whereas 59% achieved a satisfactory functional result. The advantage of this operating technique lies in its simplicity. Nevertheless, considerable experience is necessary owing to the relatively high complication rate (secondary displacement, tendon or nerve lesions, reflex sympathetic dystrophy). However, this method requires only a limited amount of time and remains a good indication for extra-articular and simple articular fractures. In the case of severe posterior comminution, the use of cancellous bone graft can help to prevent secondary dorsal impaction and its repercussion on distal radio-ulnar function.

Nasal chondrocyte-based engineered autologous cartilage tissue for repair of articular cartilage defects: an observational first-in-human trial.

PubMed

Mumme, Marcus; Barbero, Andrea; Miot, Sylvie; Wixmerten, Anke; Feliciano, Sandra; Wolf, Francine; Asnaghi, Adelaide M; Baumhoer, Daniel; Bieri, Oliver; Kretzschmar, Martin; Pagenstert, Geert; Haug, Martin; Schaefer, Dirk J; Martin, Ivan; Jakob, Marcel

2016-10-22

Articular cartilage injuries have poor repair capacity, leading to progressive joint damage, and cannot be restored predictably by either conventional treatments or advanced therapies based on implantation of articular chondrocytes. Compared with articular chondrocytes, chondrocytes derived from the nasal septum have superior and more reproducible capacity to generate hyaline-like cartilage tissues, with the plasticity to adapt to a joint environment. We aimed to assess whether engineered autologous nasal chondrocyte-based cartilage grafts allow safe and functional restoration of knee cartilage defects. In a first-in-human trial, ten patients with symptomatic, post-traumatic, full-thickness cartilage lesions (2-6 cm 2 ) on the femoral condyle or trochlea were treated at University Hospital Basel in Switzerland. Chondrocytes isolated from a 6 mm nasal septum biopsy specimen were expanded and cultured onto collagen membranes to engineer cartilage grafts (30 × 40 × 2 mm). The engineered tissues were implanted into the femoral defects via mini-arthrotomy and assessed up to 24 months after surgery. Primary outcomes were feasibility and safety of the procedure. Secondary outcomes included self-assessed clinical scores and MRI-based estimation of morphological and compositional quality of the repair tissue. This study is registered with ClinicalTrials.gov, number NCT01605201. The study is ongoing, with an approved extension to 25 patients. For every patient, it was feasible to manufacture cartilaginous grafts with nasal chondrocytes embedded in an extracellular matrix rich in glycosaminoglycan and type II collagen. Engineered tissues were stable through handling with forceps and could be secured in the injured joints. No adverse reactions were recorded and self-assessed clinical scores for pain, knee function, and quality of life were improved significantly from before surgery to 24 months after surgery. Radiological assessments indicated variable degrees of defect filling and development of repair tissue approaching the composition of native cartilage. Hyaline-like cartilage tissues, engineered from autologous nasal chondrocytes, can be used clinically for repair of articular cartilage defects in the knee. Future studies are warranted to assess efficacy in large controlled trials and to investigate an extension of indications to early degenerative states or to other joints. Deutsche Arthrose-Hilfe. Copyright © 2016 Elsevier Ltd. All rights reserved.

Accuracy of acromioclavicular joint injections.

PubMed

Wasserman, Bradley R; Pettrone, Sarah; Jazrawi, Laith M; Zuckerman, Joseph D; Rokito, Andrew S

2013-01-01

Injection to the acromioclavicular (AC) joint can be both diagnostic and therapeutic. The purpose of this study was to evaluate the accuracy of in vivo AC joint injections. Case series; Level of evidence, 4. Thirty patients with pain localized to the AC joint were injected with 1 mL of 1% lidocaine and 0.5 mL of radiographic contrast material (Isovue). Radiographs of the AC joint were taken after the injection. Each radiograph was reviewed by a musculoskeletal radiologist and graded as intra-articular, extra-articular, or partially intra-articular. Of the 30 injections performed, 13 (43.3%) were intra-articular, 7 (23.3%) were partially articular, and 10 (33.3%) were extra-articular. When the intra-articular and the partially articular groups were combined, 20 patients (66.7%) had some contrast dye in the AC joint. This study demonstrates that despite the relatively superficial location of the AC joint, the clinical accuracy of AC joint injections remains relatively low.

T1ρ MR Imaging of Human Musculoskeletal System

PubMed Central

Wang, Ligong; Regatte, Ravinder R.

2014-01-01

Magnetic resonance imaging (MRI) offers the direct visualization of human musculoskeletal (MSK) system, especially all diarthrodial tissues including cartilage, bone, menisci, ligaments, tendon, hip, synovium etc. Conventional MR imaging techniques based on T1- and T2-weighted, proton density (PD) contrast are inconclusive in quantifying early biochemically degenerative changes in MSK system in general and articular cartilage in particular. In recent years, quantitative MR parameter mapping techniques have been used to quantify the biochemical changes in articular cartilage with a special emphasis on evaluating joint injury, cartilage degeneration, and soft tissue repair. In this article, we will focus on cartilage biochemical composition, basic principles of T1ρ MR imaging, implementation of T1ρ pulse sequences, biochemical validation, and summarize the potential applications of T1ρ MR imaging technique in MSK diseases including osteoarthritis (OA), anterior cruciate ligament (ACL) injury, and knee joint repair. Finally, we will also review the potential advantages, challenges, and future prospects of T1ρ MR imaging for widespread clinical translation. PMID:24935818

99Tcm-labelled polyclonal human immunoglobulin G scintigraphy before and after intra-articular knee injection of triamcinolone hexacetonide in patients with rheumatoid arthritis.

PubMed

de Bois, M H; Arndt, J W; Tak, P P; Kluin, P M; van der Velde, E A; Pauwels, E K; Breedveld, F C

1993-10-01

The ability of 99Tcm-labelled polyclonal human immunoglobulin G (99Tcm-IgG) scintigraphy to monitor intra-individual variation in arthritis activity was studied in seven patients with rheumatoid arthritis (RA). These patients were treated with an intra-articular injection of 20 mg triamcinolone hexacetonide. The results of semiquantitative 99Tcm-IgG scintigraphy were compared with the degree of joint swelling and the histological changes observed in synovial biopsies before and 14 days after the injection. In all seven patients the local treatment resulted in a decreased arthritis activity of the treated knee as measured clinically or histologically. This decrease was parallelled, in all patients except one, by a lower uptake of 99Tcm-IgG after the injection when compared to uptake prior to treatment. This study shows that 99Tcm-IgG scintigraphy is able to reflect intra-individual variations in arthritis activity in patients with RA.

Synthesis and Preclinical Characterization of a Cationic Iodinated Imaging Contrast Agent (CA4+) and Its Use for Quantitative Computed Tomography of Ex Vivo Human Hip Cartilage.

PubMed

Stewart, Rachel C; Patwa, Amit N; Lusic, Hrvoje; Freedman, Jonathan D; Wathier, Michel; Snyder, Brian D; Guermazi, Ali; Grinstaff, Mark W

2017-07-13

Contrast agents that go beyond qualitative visualization and enable quantitative assessments of functional tissue performance represent the next generation of clinically useful imaging tools. An optimized and efficient large-scale synthesis of a cationic iodinated contrast agent (CA4+) is described for imaging articular cartilage. Contrast-enhanced CT (CECT) using CA4+ reveals significantly greater agent uptake of CA4+ in articular cartilage compared to that of similar anionic or nonionic agents, and CA4+ uptake follows Donnan equilibrium theory. The CA4+ CECT attenuation obtained from imaging ex vivo human hip cartilage correlates with the glycosaminoglycan content, equilibrium modulus, and coefficient of friction, which are key indicators of cartilage functional performance and osteoarthritis stage. Finally, preliminary toxicity studies in a rat model show no adverse events, and a pharmacokinetics study documents a peak plasma concentration 30 min after dosing, with the agent no longer present in vivo at 96 h via excretion in the urine.

T₁ρ MRI of human musculoskeletal system.

PubMed

Wang, Ligong; Regatte, Ravinder R

2015-03-01

Magnetic resonance imaging (MRI) offers the direct visualization of the human musculoskeletal (MSK) system, especially all diarthrodial tissues including cartilage, bone, menisci, ligaments, tendon, hip, synovium, etc. Conventional MRI techniques based on T1 - and T2 -weighted, proton density (PD) contrast are inconclusive in quantifying early biochemically degenerative changes in MSK system in general and articular cartilage in particular. In recent years, quantitative MR parameter mapping techniques have been used to quantify the biochemical changes in articular cartilage, with a special emphasis on evaluating joint injury, cartilage degeneration, and soft tissue repair. In this article we focus on cartilage biochemical composition, basic principles of T1ρ MRI, implementation of T1ρ pulse sequences, biochemical validation, and summarize the potential applications of the T1ρ MRI technique in MSK diseases including osteoarthritis (OA), anterior cruciate ligament (ACL) injury, and knee joint repair. Finally, we also review the potential advantages, challenges, and future prospects of T1ρ MRI for widespread clinical translation. © 2014 Wiley Periodicals, Inc.

[Subchondral drilling method combined with gum-bletilla complex to repair articular cartilage defects].

PubMed

Huang, Yong; Wang, Xin-Ling; Qiu, Heng; Xiao, Yi-Cheng; Wu, Zong-Hong; Xu, Jian

2018-02-01

Two types(A model and B model) of articular cartilage defect models were prepared by using adult New Zealand white rabbits. A model group was applied by drilling without through subchondral bone, whose right joint was repaired by composite scaffolds made by seed cell, gum-bletilla as well as Pluronic F-127, and left side was blank control. B model group was applied by subchondral drilling method, whose right joint was repaired by using composite scaffolds made by gum-bletilla and Pluronic F-127 without seed cells, and left side was blank control. Autogenous contrast was used in both model types. In addition, another group was applied with B model type rabbits, which was repaired with artificial complex material of Pluronic F-127 in both joint sides. 4, 12 and 24 weeks after operation, the animals were sacrificed and the samples were collected from repaired area for staining with HE, typeⅡcollagen immunohistochemical method, Alcian blue, and toluidine blue, and then were observed with optical microscope. Semi-quantitative scores were graded by referring to Wakitanis histological scoring standard to investigate the histomorphology of repaired tissue. Hyaline cartilage repairing was achieved in both Group A and Group B, with satisfactory results. There were no significant differences on repairing effects for articular cartilage defects between composite scaffolds made by seed cell, gum-bletilla and Pluronic F-127, and the composite scaffolds made by gum-bletilla and Pluronic F-127 without seed cell. Better repairing effects for articular cartilage defects were observed in groups with use of gum-bletilla, indicating that gum-bletilla is a vital part in composite scaffolds material. Copyright© by the Chinese Pharmaceutical Association.

Application of a Three-Dimensional Poroelastic BEM to Modeling the Biphasic Mechanics of Cell-Matrix Interactions in Articular Cartilage (REVISION)

PubMed Central

Haider, Mansoor A.; Guilak, Farshid

2009-01-01

Articular cartilage exhibits viscoelasticity in response to mechanical loading that is well described using biphasic or poroelastic continuum models. To date, boundary element methods (BEMs) have not been employed in modeling biphasic tissue mechanics. A three dimensional direct poroelastic BEM, formulated in the Laplace transform domain, is applied to modeling stress relaxation in cartilage. Macroscopic stress relaxation of a poroelastic cylinder in uni-axial confined compression is simulated and validated against a theoretical solution. Microscopic cell deformation due to poroelastic stress relaxation is also modeled. An extended Laplace inversion method is employed to accurately represent mechanical responses in the time domain. PMID:19851478

Application of a Three-Dimensional Poroelastic BEM to Modeling the Biphasic Mechanics of Cell-Matrix Interactions in Articular Cartilage (REVISION).

PubMed

Haider, Mansoor A; Guilak, Farshid

2007-06-15

Articular cartilage exhibits viscoelasticity in response to mechanical loading that is well described using biphasic or poroelastic continuum models. To date, boundary element methods (BEMs) have not been employed in modeling biphasic tissue mechanics. A three dimensional direct poroelastic BEM, formulated in the Laplace transform domain, is applied to modeling stress relaxation in cartilage. Macroscopic stress relaxation of a poroelastic cylinder in uni-axial confined compression is simulated and validated against a theoretical solution. Microscopic cell deformation due to poroelastic stress relaxation is also modeled. An extended Laplace inversion method is employed to accurately represent mechanical responses in the time domain.

Depth-varying density and organization of chondrocytes in immature and mature bovine articular cartilage assessed by 3d imaging and analysis.

PubMed

Jadin, Kyle D; Wong, Benjamin L; Bae, Won C; Li, Kelvin W; Williamson, Amanda K; Schumacher, Barbara L; Price, Jeffrey H; Sah, Robert L

2005-09-01

Articular cartilage is a heterogeneous tissue, with cell density and organization varying with depth from the surface. The objectives of the present study were to establish a method for localizing individual cells in three-dimensional (3D) images of cartilage and quantifying depth-associated variation in cellularity and cell organization at different stages of growth. Accuracy of nucleus localization was high, with 99% sensitivity relative to manual localization. Cellularity (million cells per cm3) decreased from 290, 310, and 150 near the articular surface in fetal, calf, and adult samples, respectively, to 120, 110, and 50 at a depth of 1.0 mm. The distance/angle to the nearest neighboring cell was 7.9 microm/31 degrees , 7.1 microm/31 degrees , and 9.1 microm/31 degrees for cells at the articular surface of fetal, calf, and adult samples, respectively, and increased/decreased to 11.6 microm/31 degrees , 12.0 microm/30 degrees , and 19.2 microm/25 degrees at a depth of 0.7 mm. The methodologies described here may be useful for analyzing the 3D cellular organization of cartilage during growth, maturation, aging, degeneration, and regeneration.

Depth-varying density and organization of chondrocytes in immature and mature bovine articular cartilage assessed by 3d imaging and analysis

NASA Technical Reports Server (NTRS)

Jadin, Kyle D.; Wong, Benjamin L.; Bae, Won C.; Li, Kelvin W.; Williamson, Amanda K.; Schumacher, Barbara L.; Price, Jeffrey H.; Sah, Robert L.

2005-01-01

Articular cartilage is a heterogeneous tissue, with cell density and organization varying with depth from the surface. The objectives of the present study were to establish a method for localizing individual cells in three-dimensional (3D) images of cartilage and quantifying depth-associated variation in cellularity and cell organization at different stages of growth. Accuracy of nucleus localization was high, with 99% sensitivity relative to manual localization. Cellularity (million cells per cm3) decreased from 290, 310, and 150 near the articular surface in fetal, calf, and adult samples, respectively, to 120, 110, and 50 at a depth of 1.0 mm. The distance/angle to the nearest neighboring cell was 7.9 microm/31 degrees , 7.1 microm/31 degrees , and 9.1 microm/31 degrees for cells at the articular surface of fetal, calf, and adult samples, respectively, and increased/decreased to 11.6 microm/31 degrees , 12.0 microm/30 degrees , and 19.2 microm/25 degrees at a depth of 0.7 mm. The methodologies described here may be useful for analyzing the 3D cellular organization of cartilage during growth, maturation, aging, degeneration, and regeneration.

[Histologic assessment of tissue healing of hyaline cartilage by use of semiquantitative evaluation scale].

PubMed

Vukasović, Andreja; Ivković, Alan; Jezek, Davor; Cerovecki, Ivan; Vnuk, Drazen; Kreszinger, Mario; Hudetz, Damir; Pećina, Marko

2011-01-01

Articular cartilage is an avascular and aneural tissue lacking lymph drainage, hence its inability of spontaneous repair following injury. Thus, it offers an interesting model for scientific research. A number of methods have been suggested to enhance cartilage repair, but none has yet produced significant success. The possible application of the aforementioned methods has brought about the necessity to evaluate their results. The objective of this study was to analyze results of a study of the effects of the use of TGF-beta gene transduced bone marrow clot on articular cartilage defects using ICRS visual histological assessment scale. The research was conducted on 28 skeletally mature sheep that were randomly assigned to four groups and surgically inflicted femoral chondral defects. The articular surfaces were then treated with TGF-beta1 gene transduced bone marrow clot (TGF group), GFP transduced bone marrow clot (GFP group), untransduced bone marrow clot (BM group) or left untreated (NC group). The analysis was performed by visual examination of cartilage samples and results were obtained using ICRS visual histological assessment scale. The results were subsequently subjected to statistical assessment using Kruskal-Wallis and Mann-Whitney tests. Kruskal-Wallis test yielded statistically significant difference with respect to cell distribution. Mann-Whitney test showed statistically significant difference between TGF and NC groups (P = 0.002), as well as between BM and NC groups (P = 0.002 with Bonferroni correction). Twenty-six of the twenty-eight samples were subjected to histologic and subsequent statistical analysis; two were discarded due to faulty histology technique. Our results indicated a level of certainty as to the positive effect of TGF-beta1 gene transduced bone marrow clot in restoration of articular cartilage defects. However, additional research is necessary in the field. One of the significant drawbacks on histologic assessment of cartilage samples were the errors in histologic preparation, for which some samples had to be discarded and significantly impaired the analytical quality of the others. Defects of structures surrounding the articular cartilage, e.g., subchondral bone or connective tissue, might also impair the quality of histologic analysis. Additional analyses, i.e. polarizing microscopy should be performed to determine the degree of integration of the newly formed tissue with the surrounding cartilage. The semiquantitative ICRS scale, although of great practical value, has limitations as to the objectivity of the assessment, taking into account the analytical ability of the evaluator, as well as the accuracy of semiquantitative analysis in comparison to the methods of quantitative analysis. Overall results of histologic analysis indicated that the application of TGF-beta1 gene transduced bone marrow clot could have measurable clinical effects on articular cartilage repair. The ICRS visual histological assessment scale is a valuable analytical method for cartilage repair evaluation. In this respect, further analyses of the method value would be of great importance.

[The role of the human microbiom in the pathogenesis of rheumatoid arthritis - a literature review].

PubMed

Krajewska-Włodarczyk, Magdalena

Rheumatoid arthritis is a chronic, progressive, autoimmune disease with numerous articular, extra-articular and systemic manifestations. The cause of rheumatoid arthritis is multifactorial including genetic and environmental factors. Recent advantages in sequencing techniques have allowed the deep characterization of the human microbiota. Available evidence confirms the existence of an association between dysbiosis and rheumatoid arthritis but it still remains unclear whether alterations in the microbiome are a pathogenic cause or an effect of autoimmune disease. In patients with rheumatoid arthritis the most supported association between disease and microbiota is with the oral dysbiosis usually observed in patients with periodontitis. Given the strong variability and abundance of microbes living in close relation with human host, it becomes a difficult task to define what should be considered the favorable microbiome. There is need for broader studies to establish how the human microbiome contributes to disease susceptibility, and to characterize the role of microbial diversity in the pathogenesis of rheumatoid arthritis, disease manifestation, and progression. The identification of dysbiosis specific for rheumatoid arthritis and the understanding of the dynamic interaction between microbiota and their host may help in establishing an individualized management for each patient with rheumatoid arthritis, and achieve a better efficacy of the therapy.

Physical articular examination in the activity of rheumatoid arthritis: a systematic review of the literature : Systematic review of the literature regarding physical examination in rheumatoid arthritis.

PubMed

Medina, Yimy F; Ruíz-Gaviria, Rafael Eduardo; Buitrago-Lopez, Adriana; Villota, Catalina

2018-06-01

To summarize evidence concerning the articular examination needed to determine rheumatoid arthritis (RA) activity (follow-up or control) via a systematic review. A search of Medline, Embase, Lilacs, SciELO, the Web of Science, the National Technical Reports Library, and the reference lists of relevant studies through March 2017 was conducted using a systematic methodology to identify studies of patients with RA older than 18 years in which a detailed description of the physical examination or a description of the components of the articular examination was provided. Of 8322 references, 74 studies were included according to the selection criteria, and 6 references were ultimately included at the end of the review. Most of the included studies (n = 5) were associated with a moderate risk of bias. There was great variability among the studies and the articular examination methods used. Some studies presented the examination with a complete specification of the technique (n = 2), the consensus of rheumatologists (n = 2), or training through audiovisual materials and face-to-face courses (n = 2), but none of the studies explicitly showed the technique by which the physical examination was performed. Despite the importance of the clinical evaluation and physical examination of patients with RA for diagnosis, prognosis, clinimetrics, and follow-up, evidence concerning how to perform the articular examination is scarce.

“Soft that molds the hard:” Geometric morphometry of lateral atlantoaxial joints focusing on the role of cartilage in changing the contour of bony articular surfaces

PubMed Central

Prasad, Prashant Kumar; Salunke, Pravin; Sahni, Daisy; Kalra, Parveen

2017-01-01

Purpose: The existing literature on lateral atlantoaxial joints is predominantly on bony facets and is unable to explain various C1-2 motions observed. Geometric morphometry of facets would help us in understanding the role of cartilages in C1-2 biomechanics/kinematics. Objective: Anthropometric measurements (bone and cartilage) of the atlantoaxial joint and to assess the role of cartilages in joint biomechanics. Materials and Methods: The authors studied 10 cadaveric atlantoaxial lateral joints with the articular cartilage in situ and after removing it, using three-dimensional laser scanner. The data were compared using geometric morphometry with emphasis on surface contours of articulating surfaces. Results: The bony inferior articular facet of atlas is concave in both sagittal and coronal plane. The bony superior articular facet of axis is convex in sagittal plane and is concave (laterally) and convex medially in the coronal plane. The bony articulating surfaces were nonconcordant. The articular cartilages of both C1 and C2 are biconvex in both planes and are thicker than the concavities of bony articulating surfaces. Conclusion: The biconvex structure of cartilage converts the surface morphology of C1-C2 bony facets from concave on concavo-convex to convex on convex. This reduces the contact point making the six degrees of freedom of motion possible and also makes the joint gyroscopic. PMID:29403249

Juxta-articular Plate Fixation in Distal Radius Intra-articular Fractures with Accompanying Volar Free Fragments beyond the Watershed Line

PubMed Central

Lee, Jun-Ku; Lee, Soo-Hyun; Sim, Young-Suk; Kim, Tae-Ho; Baek, Eugene

2018-01-01

Background Although distal radius fractures (DRF) are common fractures, intra-articular comminuted DRF with volar free fragments are uncommon. There is considerable difficulty in the fixation of free fragments beyond the watershed line using the existing volar locking plate. We aimed to examine the efficacy and potential complications associated with the use of juxta-articular volar plates in intra-articular DRF accompanied by free fragments beyond the watershed line. Methods The patients were enrolled in a consecutive manner between 2007 and 2016. In cases of DRF with free fragments beyond the watershed line, we employed a 2.4-mm small fragment juxta-articular volar locking compression plate using a volar Henry approach. A total of 32 patients were included in this study. There were 15 males and 17 females with a mean age of 52.3 years (range, 33 to 69 years). The mean follow-up period was 14.5 months (range, 10 to 24 months). Preoperative radiographs and three-dimensional computed tomography images were used to analyze fracture patterns and assess the free fragments beyond the watershed line. The mean number of free fracture fragments beyond the watershed line was 2.33. Plain radiographs of immediate postoperative and last follow-up were used to confirm fracture union, incongruence, radial height, volar tilt, radial inclination, and arthritic changes. For functional assessment, we measured grip strength, range of motion (ROM), modified Mayo wrist score (MMWS) and determined Disabilities of Arm, Shoulder and Hand (DASH) scores at the last follow-up. Postoperative complications were monitored during the follow-up period. Results All patients obtained sound union without significant complications. At the last follow-up, 16 cases presented with an articular step-off of more than 1 mm (mean, 1.10 mm). The mean MMWS was 76.3 (range, 55 to 90), mean DASH score was 15.38 (range, 9 to 22), mean visual analogue scale score for pain was 1.2 and mean grip strength was 75.5% of the opposite side. The mean ROM was 74.3° for volar flexion and 71.5° for dorsiflexion. Conclusions In cases of intra-articular DRF with free fragments beyond the watershed line, a volar approach with use of a juxtaarticular plate provided favorable outcomes without significant complications. PMID:29854335

A randomized controlled trial of nonoperative treatment versus open reduction and internal fixation for stable, displaced, partial articular fractures of the radial head: the RAMBO trial

PubMed Central

2014-01-01

Background The choice between operative or nonoperative treatment is questioned for partial articular fractures of the radial head that have at least 2 millimeters of articular step-off on at least one radiograph (defined as displaced), but less than 2 millimeter of gap between the fragments (defined as stable) and that are not associated with an elbow dislocation, interosseous ligament injury, or other fractures. These kinds of fractures are often classified as Mason type-2 fractures. Retrospective comparative studies suggest that operative treatment might be better than nonoperative treatment, but the long-term results of nonoperative treatment are very good. Most experts agree that problems like reduced range of motion, painful crepitation, nonunion or bony ankylosis are infrequent with both nonoperative and operative treatment of an isolated displaced partial articular fracture of the radial head, but determining which patients will have problems is difficult. A prospective, randomized comparison would help minimize bias and determine the balance between operative and nonoperative risks and benefits. Methods/Design The RAMBO trial (Radial Head – Amsterdam – Amphia – Boston - Others) is an international prospective, randomized, multicenter trial. The primary objective of this study is to compare patient related outcome defined by the ‘Disabilities of Arm, Shoulder and Hand (DASH) score’ twelve months after injury between operative and nonoperative treated patients. Adult patients with partial articular fractures of the radial head that comprise at least 1/3rd of the articular surface, have ≥ 2 millimeters of articular step-off but less than 2 millimeter of gap between the fragments will be enrolled. Secondary outcome measures will be the Mayo Elbow Performance Index (MEPI), the Oxford Elbow Score (OES), pain intensity through the ‘Numeric Rating Scale’, range of motion (flexion arc and rotational arc), radiographic appearance of the fracture (heterotopic ossification, radiocapitellar and ulnohumeral arthrosis, fracture healing, and signs of implant loosening or breakage) and adverse events (infection, nerve injury, secondary interventions) after one year. Discussion The successful completion of this trial will provide evidence on the best treatment for stable, displaced, partial articular fractures of the radial head. Trial registration The trial is registered at the Dutch Trial Register: NTR3413. PMID:24885637

Dual Contrast CT Method Enables Diagnostics of Cartilage Injuries and Degeneration Using a Single CT Image.

PubMed

Saukko, Annina E A; Honkanen, Juuso T J; Xu, Wujun; Väänänen, Sami P; Jurvelin, Jukka S; Lehto, Vesa-Pekka; Töyräs, Juha

2017-12-01

Cartilage injuries may be detected using contrast-enhanced computed tomography (CECT) by observing variations in distribution of anionic contrast agent within cartilage. Currently, clinical CECT enables detection of injuries and related post-traumatic degeneration based on two subsequent CT scans. The first scan allows segmentation of articular surfaces and lesions while the latter scan allows evaluation of tissue properties. Segmentation of articular surfaces from the latter scan is difficult since the contrast agent diffusion diminishes the image contrast at surfaces. We hypothesize that this can be overcome by mixing anionic contrast agent (ioxaglate) with bismuth oxide nanoparticles (BINPs) too large to diffuse into cartilage, inducing a high contrast at the surfaces. Here, a dual contrast method employing this mixture is evaluated by determining the depth-wise X-ray attenuation profiles in intact, enzymatically degraded, and mechanically injured osteochondral samples (n = 3 × 10) using a microCT immediately and at 45 min after immersion in contrast agent. BiNPs were unable to diffuse into cartilage, producing high contrast at articular surfaces. Ioxaglate enabled the detection of enzymatic and mechanical degeneration. In conclusion, the dual contrast method allowed detection of injuries and degeneration simultaneously with accurate cartilage segmentation using a single scan conducted at 45 min after contrast agent administration.

Operative treatment of intra-articular calcaneal fractures with calcaneal plates and its complications

PubMed Central

Rak, Vaclav; Ira, Daniel; Masek, Michal

2009-01-01

Background: In a retrospective study we analysed intra-articular calcaneal fracture treatment by comparing results and complications related to fracture stabilization with nonlocking calcaneal plates and locking compression plates. Materials and Methods: We performed 76 osteosynthesis (67 patients) of intra-articular calcaneal fractures using the standard extended lateral approach from February 2004 to October 2007. Forty-two operations using nonlocking calcaneal plates (group A) were performed during the first three years, and 34 calcaneal fractures were stabilized using locking compression plates (group B) in 2007. In the Sanders type IV fractures, reconstruction of the calcaneal shape was attempted. Depending on the type of late complication, we performed subtalar arthroscopy in six cases, arthroscopically assisted subtalar distraction bone block arthrodesis in six cases, and plate removal with lateral-wall decompression in five cases. The patients were evaluated by the AOFAS Ankle-Hindfoot Scale. Results: Wound healing complications were 7/42 (17%) in group A and 1/34 (3%) in group B. No patient had deep osseous infection or foot rebound compartment syndrome. Preoperative size of Böhler's angle correlated with postoperative clinical results in both groups. There were no late complications necessitating corrective procedure or arthroscopy until December 2008 in Group B. All late complications ccurred in Group A. The overall results according to the AOFAS Ankle Hindfoot Scale were good or excellent in 23/42 (55%) in group A and in 30/34 (85%) in group B. Conclusion: Open reduction and internal fixation of intra-articular calcaneal fractures has become a standard surgical method. Fewer complications and better results related to treatment with locking compression plates confirmed in comparison to nonlocking ones were noted for all Sanders types of intra-articular calcaneal fractures. Age and Sanders type IV fractures are not considered to be the contraindications to surgery. PMID:19838350

Visualization of the extra-articular portion of the long head of the biceps tendon during intra-articular shoulder arthroscopy.

PubMed

Festa, Anthony; Allert, Jesse; Issa, Kimona; Tasto, James P; Myer, Jonathan J

2014-11-01

To quantify the amount of the extra-articular long head of the biceps tendon (LHBT) seen during intra-articular shoulder arthroscopy by pulling the tendon into the joint with a probe through an anterior portal while viewing through a standard posterior portal. Intra-articular shoulder arthroscopy was performed on 10 forequarter cadaveric specimens. The extra-articular portion of the LHBT was evaluated by pulling the tendon into the joint with an arthroscopic probe inserted through an anterior portal. The tendon was marked at the pulley insertion on the humerus with a vascular clip before and after the tendon was pulled into the joint. An open deltopectoral approach was performed, and the amount of extra-articular tendon visualized was calculated as an absolute amount and in relation to nearby anatomic structures. An additional 1.9 cm (range, 1.4 to 2.6 cm) of extra-articular LHBT was viewed by pulling the tendon into the joint with an arthroscopic probe through an anterior portal during shoulder arthroscopy. This represented 30.8% of the extra-articular portion of the tendon, 47.7% of tendon in the bicipital groove, and 76.3% of the tendon that lies under the area from the pulley insertion to the distal edge of the transverse humeral ligament. During intra-articular shoulder arthroscopy, the extra-articular portion of the LHBT is incompletely visualized by pulling the tendon into the joint with a probe placed through an anterior portal while viewing through a standard posterior portal. An additional extra-articular portion of the LHBT may be viewed by pulling the tendon into the joint with an arthroscopic probe during shoulder arthroscopy. Copyright © 2014 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Cartilage Repair With Autologous Bone Marrow Mesenchymal Stem Cell Transplantation: Review of Preclinical and Clinical Studies.

PubMed

Yamasaki, Shinya; Mera, Hisashi; Itokazu, Maki; Hashimoto, Yusuke; Wakitani, Shigeyuki

2014-10-01

Clinical trials of various procedures, including bone marrow stimulation, mosaicplasty, and autologous chondrocyte implantation, have been explored to treat articular cartilage defects. However, all of them have some demerits. We focused on autologous culture-expanded bone marrow mesenchymal stem cells (BMSC), which can proliferate without losing their capacity for differentiation. First, we transplanted BMSC into the defective articular cartilage of rabbit and succeeded in regenerating osteochondral tissue. We then applied this transplantation in humans. Our previous reports showed that treatment with BMSC relieves the clinical symptoms of chondral defects in the knee and elbow joint. We investigated the efficacy of BMSC for osteoarthritic knee treated with high tibial osteotomy, by comparing 12 BMSC-transplanted patients with 12 cell-free patients. At 16-month follow-up, although the difference in clinical improvement between both groups was not significant, the arthroscopic and histological grading score was better in the cell-transplanted group. At the over 10-year follow-up, Hospital for Special Surgery knee scores improved to 76 and 73 in the BMSC-transplanted and cell-free groups, respectively, which were better than preoperative scores. Additionally, neither tumors nor infections were observed in all patients, and in the clinical study, we have never observed hypertrophy of repaired tissue, thereby guaranteeing the clinical safety of this therapy. Although we have never observed calcification above the tidemark in rabbit model and human histologically, the repair cartilage was not completely hyaline cartilage. To elucidate the optimum conditions for cell therapy, other stem cells, culture conditions, growth factors, and gene transfection methods should be explored.

Techniques of Force and Pressure Measurement in the Small Joints of the Wrist.

PubMed

Schreck, Michael J; Kelly, Meghan; Canham, Colin D; Elfar, John C

2018-01-01

The alteration of forces across joints can result in instability and subsequent disability. Previous methods of force measurements such as pressure-sensitive films, load cells, and pressure-sensing transducers have been utilized to estimate biomechanical forces across joints and more recent studies have utilized a nondestructive method that allows for assessment of joint forces under ligamentous restraints. A comprehensive review of the literature was performed to explore the numerous biomechanical methods utilized to estimate intra-articular forces. Methods of biomechanical force measurements in joints are reviewed. Methods such as pressure-sensitive films, load cells, and pressure-sensing transducers require significant intra-articular disruption and thus may result in inaccurate measurements, especially in small joints such as those within the wrist and hand. Non-destructive methods of joint force measurements either utilizing distraction-based joint reaction force methods or finite element analysis may offer a more accurate assessment; however, given their recent inception, further studies are needed to improve and validate their use.

Mathematics as a Conduit for Translational Research in Post-Traumatic Osteoarthritis

PubMed Central

Ayati, Bruce P.; Kapitanov, Georgi I.; Coleman, Mitchell C.; Anderson, Donald D.; Martin, James A.

2016-01-01

Biomathematical models offer a powerful method of clarifying complex temporal interactions and the relationships among multiple variables in a system. We present a coupled in silico biomathematical model of articular cartilage degeneration in response to impact and/or aberrant loading such as would be associated with injury to an articular joint. The model incorporates fundamental biological and mechanical information obtained from explant and small animal studies to predict post-traumatic osteoarthritis (PTOA) progression, with an eye toward eventual application in human patients. In this sense, we refer to the mathematics as a “conduit of translation”. The new in silico framework presented in this paper involves a biomathematical model for the cellular and biochemical response to strains computed using finite element analysis. The model predicts qualitative responses presently, utilizing system parameter values largely taken from the literature. To contribute to accurate predictions, models need to be accurately parameterized with values that are based on solid science. We discuss a parameter identification protocol that will enable us to make increasingly accurate predictions of PTOA progression using additional data from smaller scale explant and small animal assays as they become available. By distilling the data from the explant and animal assays into parameters for biomathematical models, mathematics can translate experimental data to clinically relevant knowledge. PMID:27653021

[Research progress of articular cartilage scaffold for tissue engineering].

PubMed

Liu, Qingyu; Wang, Fuyou; Yang, Liu

2012-10-01

To review the research progress of articular cartilage scaffold materials and look into the future development prospects. Recent literature about articular cartilage scaffold for tissue engineering was reviewed, and the results from experiments and clinical application about natural and synthetic scaffold materials were analyzed. The design of articular cartilage scaffold for tissue engineering is vital to articular cartilage defects repair. The ideal scaffold can promote the progress of the cartilage repair, but the scaffold materials still have their limitations. It is necessary to pay more attention to the research of the articular cartilage scaffold, which is significant to the repair of cartilage defects in the future.

Mapping the articular contact area of the long head of the biceps tendon on the humeral head.

PubMed

Morris, Brent J; Byram, Ian R; Lathrop, Ray A; Dunn, Warren R; Kuhn, John E

2014-01-01

The purpose of this investigation was to calculate the contact surface area of the long head of the biceps (LHB) in neutral position and abduction. We sought to determine whether the LHB articulates with the humeral head in a consistent pattern comparing articular contact area in neutral position and abduction. Eleven fresh frozen matched cadaveric shoulders were analyzed. The path of the biceps tendon on the articular surface of the humeral head and the total articular surface were digitized using a MicronTracker 2 H3-60 three-dimensional optical tracker. Contact surface area was significantly less in abduction than in neutral position (P = 0.002) with a median ratio of 41% (36%, 47.5%). Ratios of contact area in neutral position to full articular surface area were consistent between left and right shoulders (rho = 1, P = 0.017) as were ratios of abduction area to full articular surface area (rho = 0.97, P = 0.005). The articular contact surface area is significantly greater in neutral position than abduction. The ratios of articular contact surface areas to total humeral articular surface areas have a narrow range and are consistent between left and right shoulders of the same cadaver.

Tribological changes in the articular cartilage of a human femoral head with avascular necrosis.

PubMed

Seo, Eun-Min; Shrestha, Suman K; Duong, Cong-Truyen; Sharma, Ashish Ranjan; Kim, Tae-Woo; Vijayachandra, Ayyappan; Thompson, Mark S; Cho, Myung Guk; Park, Sungchan; Kim, Kwanghoon; Park, Seonghun; Lee, Sang-Soo

2015-06-29

The present study evaluated the tribological properties of the articular cartilage surface of the human femoral head with postcollapse stage avascular necrosis (AVN) using atomic force microscopy. The cartilage surface in the postcollapse stage AVN of the femoral head was reported to resemble those of disuse conditions, which suggests that the damage could be reversible and offers the possibilities of success of head-sparing surgeries. By comparing the tribological properties of articular cartilage in AVN with that of osteoarthritis, the authors intended to understand the cartilage degeneration mechanism and reversibility of AVN. Human femoral heads with AVN were explanted from the hip replacement surgery of four patients (60-83 years old). Nine cylindrical cartilage samples (diameter, 5 mm and height, 0.5 mm) were sectioned from the weight-bearing areas of the femoral head with AVN, and the cartilage surface was classified according to the Outerbridge Classification System (AVN0, normal; AVN1, softening and swelling; and AVN2, partial thickness defect and fissuring). Tribological properties including surface roughness and frictional coefficients and histochemistry including Safranin O and lubricin staining were compared among the three groups. The mean surface roughness Rq values of AVN cartilage increased significantly with increasing Outerbridge stages: Rq = 137 ± 26 nm in AVN0, Rq = 274 ± 49 nm in AVN1, and Rq = 452 ± 77 nm in AVN2. Significant differences in Rq were observed among different Outerbridge stages in all cases (p < 0.0001). The frictional coefficients (μ) also increased with increasing Outerbridge stages. The frictional coefficient values were μ = 0.115 ± 0.034 in AVN0, μ = 0.143 ± 0.025 in AVN1, and μ = 0.171 ± 0.039 in AVN2. Similarly to the statistical analysis of surface roughness, significant statistical differences were detected between different Outerbridge stages in all cases (p < 0.05). Both surface roughness and frictional coefficient of cartilage, which were linearly correlated, increased with increasing Outerbridge stages in postcollapse AVN. The underlying mechanism of these results can be related to proteoglycan loss within the articular cartilage that is also observed in osteoarthritis. With regard to the tribological properties, the cartilage degeneration mechanism in AVN was similar to that of osteoarthritis without reversibility.

Simultaneous Treatment with Subcutaneous Injection of Golimumab and Intra-articular Injection of Triamcinolone Acetonide (K-Method) in Patients with Rheumatoid Arthritis Undergoing Switching of Biologics: Retrospective Case–Control Study

PubMed Central

Kanbe, Katsuaki; Chiba, Junji; Inoue, Yasuo; Taguchi, Masashi; Yabuki, Akiko; Deguchi, Tomohiko

2016-01-01

BACKGROUND Tight control of severe rheumatoid arthritis (RA) in patients with high disease activity, even when using biologics, is sometimes difficult using a treat-to-target strategy. Switching from one biologic to another is associated with lower efficacy than that in treatment-naive cases. We developed the K-method that involves simultaneous treatment with golimumab and intra-articular joint injection of triamcinolone acetonide (TA) in patients undergoing switching of biologics. We performed this retrospective case–control study to investigate the efficacy of achieving an immediate treatment response using the K-method. METHODS This study involved 20 patients with RA (control group, 10 patients; K-method group, 10 patients). Patients in the control group were switched to golimumab from other biologics without intra-articular injection of TA. The K-method involved injection of 1 mL of TA (40 mg/mL) and 2 mL of 1% lidocaine hydrochloride into swollen or painful joints on the same day as golimumab treatment. A quick response one day after treatment was compared between the two groups according to the disease activity score 28 based on C-reactive protein (DAS28 CRP), clinical disease activity index (CDAI), simplified disease activity index (SDAI), European League Against Rheumatism (EULAR) response, and remission rate. These parameters were investigated for 24 weeks. RESULTS The K-method group showed significant improvements in DAS28 CRP, CDAI, and SDAI at one day, 12 weeks, and 24 weeks compared with the control group. The number of swollen and tender joints and the patient and doctor global visual analog scale scores were also significantly different between the two groups. The remission rates based on DAS28 CRP were 30% at one day, 50% at 12 weeks, and 60% at 24 weeks in the K-method group. The EULAR good/moderate response rates were 80% at one day, 90% at 12 weeks, and 90% at 24 weeks in the K-method group; however, these rates were only 10%, 40%, and 40%, respectively, in the control group. No adverse events occurred in either group. CONCLUSION Simultaneous treatment with biologics and intra-articular injection of TA is useful for cases involving switching of biologics for RA. This strategy is safe and practical for RA treatment. PMID:27081319

[Technique and value of direct MR arthrography applying articular distraction].

PubMed

Becce, Fabio; Wettstein, Michael; Guntern, Daniel; Mouhsine, Elyazid; Palhais, Nuno; Theumann, Nicolas

2010-02-24

Direct MR arthrography has a better diagnostic accuracy than MR imaging alone. However, contrast material is not always homogeneously distributed in the articular space. Lesions of cartilage surfaces or intra-articular soft tissues can thus be misdiagnosed. Concomitant application of axial traction during MR arthrography leads to articular distraction. This enables better distribution of contrast material in the joint and better delineation of intra-articular structures. Therefore, this technique improves detection of cartilage lesions. Moreover, the axial stress applied on articular structures may reveal lesions invisible on MR images without traction. Based on our clinical experience, we believe that this relatively unknown technique is promising and should be further developed.

Benefits of Ilizarov automated bone distraction for nerves and articular cartilage in experimental leg lengthening

PubMed Central

Shchudlo, Nathalia; Varsegova, Tatyana; Stupina, Tatyana; Shchudlo, Michael; Saifutdinov, Marat; Yemanov, Andrey

2017-01-01

AIM To determine peculiarities of tissue responses to manual and automated Ilizarov bone distraction in nerves and articular cartilage. METHODS Twenty-nine dogs were divided in two experimental groups: Group M - leg lengthening with manual distraction (1 mm/d in 4 steps), Group A - automated distraction (1 mm/d in 60 steps) and intact group. Animals were euthanized at the end of distraction, at 30th day of fixation in apparatus and 30 d after the fixator removal. M-responses in gastrocnemius and tibialis anterior muscles were recorded, numerical histology of peroneal and tibialis nerves and knee cartilage semi-thin sections, scanning electron microscopy and X-ray electron probe microanalysis were performed. RESULTS Better restoration of M-response amplitudes in leg muscles was noted in A-group. Fibrosis of epineurium with adipocytes loss in peroneal nerve, subperineurial edema and fibrosis of endoneurium in some fascicles of both nerves were noted only in M-group, shares of nerve fibers with atrophic and degenerative changes were bigger in M-group than in A-group. At the end of experiment morphometric parameters of nerve fibers in peroneal nerve were comparable with intact nerve only in A-group. Quantitative parameters of articular cartilage (thickness, volumetric densities of chondrocytes, percentages of isogenic clusters and empty cellular lacunas, contents of sulfur and calcium) were badly changed in M-group and less changed in A-group. CONCLUSION Automated Ilizarov distraction is more safe method of orthopedic leg lengthening than manual distraction in points of nervous fibers survival and articular cartilage arthrotic changes. PMID:28979852

3-D segmentation of articular cartilages by graph cuts using knee MR images from osteoarthritis initiative

NASA Astrophysics Data System (ADS)

Shim, Hackjoon; Lee, Soochan; Kim, Bohyeong; Tao, Cheng; Chang, Samuel; Yun, Il Dong; Lee, Sang Uk; Kwoh, Kent; Bae, Kyongtae

2008-03-01

Knee osteoarthritis is the most common debilitating health condition affecting elderly population. MR imaging of the knee is highly sensitive for diagnosis and evaluation of the extent of knee osteoarthritis. Quantitative analysis of the progression of osteoarthritis is commonly based on segmentation and measurement of articular cartilage from knee MR images. Segmentation of the knee articular cartilage, however, is extremely laborious and technically demanding, because the cartilage is of complex geometry and thin and small in size. To improve precision and efficiency of the segmentation of the cartilage, we have applied a semi-automated segmentation method that is based on an s/t graph cut algorithm. The cost function was defined integrating regional and boundary cues. While regional cues can encode any intensity distributions of two regions, "object" (cartilage) and "background" (the rest), boundary cues are based on the intensity differences between neighboring pixels. For three-dimensional (3-D) segmentation, hard constraints are also specified in 3-D way facilitating user interaction. When our proposed semi-automated method was tested on clinical patients' MR images (160 slices, 0.7 mm slice thickness), a considerable amount of segmentation time was saved with improved efficiency, compared to a manual segmentation approach.

Mesenchymal Stem Cells in Oriented PLGA/ACECM Composite Scaffolds Enhance Structure-Specific Regeneration of Hyaline Cartilage in a Rabbit Model

PubMed Central

Guo, Weimin; Zheng, Xifu; Zhang, Weiguo; Chen, Mingxue; Wang, Zhenyong; Hao, Chunxiang; Huang, Jingxiang; Yuan, Zhiguo; Zhang, Yu; Wang, Mingjie; Peng, Jiang; Wang, Aiyuan; Wang, Yu; Sui, Xiang; Xu, Wenjing

2018-01-01

Articular cartilage lacks a blood supply and nerves. Hence, articular cartilage regeneration remains a major challenge in orthopedics. Decellularized extracellular matrix- (ECM-) based strategies have recently received particular attention. The structure of native cartilage exhibits complex zonal heterogeneity. Specifically, the development of a tissue-engineered scaffold mimicking the aligned structure of native cartilage would be of great utility in terms of cartilage regeneration. Previously, we fabricated oriented PLGA/ACECM (natural, nanofibrous, articular cartilage ECM) composite scaffolds. In vitro, we found that the scaffolds not only guided seeded cells to proliferate in an aligned manner but also exhibited high biomechanical strength. To detect whether oriented cartilage regeneration was possible in vivo, we used mesenchymal stem cell (MSC)/scaffold constructs to repair cartilage defects. The results showed that cartilage defects could be completely regenerated. Histologically, these became filled with hyaline cartilage and subchondral bone. Moreover, the aligned structure of cartilage was regenerated and was similar to that of native tissue. In conclusion, the MSC/scaffold constructs enhanced the structure-specific regeneration of hyaline cartilage in a rabbit model and may be a promising treatment strategy for the repair of human cartilage defects. PMID:29666653

Morphology of sustentaculum tali: Biomechanical importance and correlation with angular dimensions of the talus.

PubMed

Mahato, Niladri Kumar

2011-12-01

The talus and the calcaneus share the bulk of load transmitted from the leg to the skeleton of the foot. The present study analyses the inter-relationship between the superior articular surface and the angular dimensions of the talus with the morphology of the sustentaculum tali. Identification of possible relationships between different angular parameters of the talus morphology and the sustentaculum tali in context of load transmission through the foot. One articular surface and three angular parameters at the junction of the head and the body were measured from dried human talar bones. Corresponding calcaneal samples were measured for four dimensions at the sustentaculum tali. Correlation and regression statistical values between parameters were worked out and analysed. Several parameters within the talus demonstrated significant correlations amongst themselves. The neck vertical angle showed a strong correlation with the articulating surface area below the head of the talus. The inter-relationship between articular and angular parameters within the talus demonstrates strong correlation for certain parameters. Data presented in the study may be helpful to adjust calcaneal and talar screw placement techniques, prosthesis designing and bio-mechanical studies at this important region. Copyright © 2011 Elsevier Ltd. All rights reserved.

Stem cells and other innovative intra-articular therapies for osteoarthritis: what does the future hold?

PubMed Central

2012-01-01

Osteoarthritis (OA), the most common type of arthritis in the world, is associated with suffering due to pain, productivity loss, decreased mobility and quality of life. Systemic therapies available for OA are mostly symptom modifying and have potential gastrointestinal, renal, hepatic, and cardiac side effects. BMC Musculoskeletal Disorders recently published a study showing evidence of reparative effects demonstrated by homing of intra-articularly injected autologous bone marrow stem cells in damaged cartilage in an animal model of OA, along with clinical and radiographic benefit. This finding adds to the growing literature showing the potential benefit of intra-articular (IA) bone marrow stem cells. Other emerging potential IA therapies include IL-1 receptor antagonists, conditioned autologous serum, botulinum toxin, and bone morphogenetic protein-7. For each of these therapies, trial data in humans have been published, but more studies are needed to establish that they are safe and effective. Several additional promising new OA treatments are on the horizon, but challenges remain to finding safe and effective local and systemic therapies for OA. Please see related article: http://www.biomedcentral.com/1471-2474/12/259 PMID:22551396

Mesenchymal Stem Cells in Oriented PLGA/ACECM Composite Scaffolds Enhance Structure-Specific Regeneration of Hyaline Cartilage in a Rabbit Model.

PubMed

Guo, Weimin; Zheng, Xifu; Zhang, Weiguo; Chen, Mingxue; Wang, Zhenyong; Hao, Chunxiang; Huang, Jingxiang; Yuan, Zhiguo; Zhang, Yu; Wang, Mingjie; Peng, Jiang; Wang, Aiyuan; Wang, Yu; Sui, Xiang; Xu, Wenjing; Liu, Shuyun; Lu, Shibi; Guo, Quanyi

2018-01-01

Articular cartilage lacks a blood supply and nerves. Hence, articular cartilage regeneration remains a major challenge in orthopedics. Decellularized extracellular matrix- (ECM-) based strategies have recently received particular attention. The structure of native cartilage exhibits complex zonal heterogeneity. Specifically, the development of a tissue-engineered scaffold mimicking the aligned structure of native cartilage would be of great utility in terms of cartilage regeneration. Previously, we fabricated oriented PLGA/ACECM (natural, nanofibrous, articular cartilage ECM) composite scaffolds. In vitro, we found that the scaffolds not only guided seeded cells to proliferate in an aligned manner but also exhibited high biomechanical strength. To detect whether oriented cartilage regeneration was possible in vivo, we used mesenchymal stem cell (MSC)/scaffold constructs to repair cartilage defects. The results showed that cartilage defects could be completely regenerated. Histologically, these became filled with hyaline cartilage and subchondral bone. Moreover, the aligned structure of cartilage was regenerated and was similar to that of native tissue. In conclusion, the MSC/scaffold constructs enhanced the structure-specific regeneration of hyaline cartilage in a rabbit model and may be a promising treatment strategy for the repair of human cartilage defects.

Rutin protects rat articular chondrocytes against oxidative stress induced by hydrogen peroxide through SIRT1 activation.

PubMed

Na, Ji-Young; Song, Kibbeum; Kim, Sokho; Kwon, Jungkee

2016-05-13

The progressive degeneration and ossification of articular chondrocytes are main symptoms in the pathogenesis of osteoarthritis (OA). Several flavonoids may provide an adjunctive alternative for the management of moderate OA in humans. Rutin, a natural flavone derivative (quercetin-3-rhamnosylglucoside), is well known for its potent anti-inflammatory and anti-oxidant properties against oxidative stress. However, the protective function of rutin related to OA, which is characterized by deterioration of articular cartilage, remains unclear. The present study investigated the protective effects of rutin, an activator of silent information regulator 1 (SIRT1), involved in the inhibition of NF-κB/MAPK signaling pathway in hydrogen peroxide (H2O2)-induced oxidative stress in rat chondrocytes. SIRT1 activation by rutin attenuated levels of inflammatory cytokines and NF-κB/MAPK signaling, whereas the inhibition of SIRT1 by sirtinol counteracted the beneficial effects of rutin in H2O2-treated chondrocytes. The findings of these studies suggested the potential involvement of SIRT1 in the pathogenesis of OA, and indicated that rutin is a possible therapeutic option for OA. Copyright © 2016 Elsevier Inc. All rights reserved.

Prediction of the articular eminence shape in a patient with unilateral hypoplasia of the right mandibular ramus before and after distraction osteogenesis-A simulation study.

PubMed

de Zee, Mark; Cattaneo, Paolo M; Svensson, Peter; Pedersen, Thomas K; Melsen, Birte; Rasmussen, John; Dalstra, Michel

2009-05-29

The aim of this work was to predict the shape of the articular eminence in a patient with unilateral hypoplasia of the right mandibular ramus before and after distraction osteogenesis (DO). Using a patient-specific musculoskeletal model of the mandible the hypothesis that the observed differences in this patient in the left and right articular eminence inclinations were consistent with minimisation of joint loads was tested. Moreover, a prediction was made of the final shape of the articular eminence after DO when the expected remodelling has reached a steady state. The individual muscle forces and the average TMJ loading were computed for each combination of articular eminence angles both before and after DO. This exhaustive parameter study provides a full overview of average TMJ loading depending on the angles of the articular eminences. Before DO the parameter study resulted in different articular eminence inclinations between left and right sides consistent with patient data obtained from CT scans, indicating that in this patient the articular eminence shapes result from minimisation of joint loads. The simulation model predicts development of almost equal articular eminence shapes after DO. The same tendency was observed in cone beam CT scans (NewTom) of the patient taken 6.5 years after surgery.

Rheumatoid arthritis (RA)-specific autoantibodies in patients with interstitial lung disease and absence of clinically apparent articular RA.

PubMed

Gizinski, Alison M; Mascolo, Margherita; Loucks, Jennifer L; Kervitsky, Alma; Meehan, Richard T; Brown, Kevin K; Holers, V Michael; Deane, Kevin D

2009-05-01

The purpose of this study was to identify rheumatoid arthritis (RA)-related autoantibodies in subjects with interstitial lung disease (ILD) and no articular findings of RA, supporting the hypothesis that RA-related autoimmunity may be generated in non-articular sites, such as the lung. This was a retrospective chart review utilizing clinic databases of patients with ILD to identify cases with lung disease, RA-related autoantibody positivity, and no clinical evidence of articular RA. Four patients with ILD, RF, and anti-CCP positivity and no articular findings of RA were identified. All four patients were male with a mean age at time of diagnosis of ILD of 70 years old. All had a history of smoking. Three patients died within 2 years of diagnosis of ILD and never developed articular symptoms consistent with RA; the final case met full criteria for articular RA several months after stopping immunosuppressive treatment for ILD. RF and anti-CCP can be present in smokers with ILD without clinical evidence of articular RA and in one case symptomatic ILD and autoantibody positivity preceded the development of articular RA. These findings suggest that RA-specific autoimmunity may be generated due to immunologic interactions in the lung and may be related to environmental factors such as smoking.

Mesenchyme-specific knockout of ESET histone methyltransferase causes ectopic hypertrophy and terminal differentiation of articular chondrocytes.

PubMed

Lawson, Kevin A; Teteak, Colin J; Zou, Junhui; Hacquebord, Jacques; Ghatan, Andrew; Zielinska-Kwiatkowska, Anna; Fernandes, Russell J; Chansky, Howard A; Yang, Liu

2013-11-08

The exact molecular mechanisms governing articular chondrocytes remain unknown in skeletal biology. In this study, we have found that ESET (an ERG-associated protein with a SET domain, also called SETDB1) histone methyltransferase is expressed in articular cartilage. To test whether ESET regulates articular chondrocytes, we carried out mesenchyme-specific deletion of the ESET gene in mice. ESET knock-out did not affect generation of articular chondrocytes during embryonic development. Two weeks after birth, there was minimal qualitative difference at the knee joints between wild-type and ESET knock-out animals. At 1 month, ectopic hypertrophy, proliferation, and apoptosis of articular chondrocytes were seen in the articular cartilage of ESET-null animals. At 3 months, additional signs of terminal differentiation such as increased alkaline phosphatase activity and an elevated level of matrix metalloproteinase (MMP)-13 were found in ESET-null cartilage. Staining for type II collagen and proteoglycan revealed that cartilage degeneration became progressively worse from 2 weeks to 12 months at the knee joints of ESET knock-out mutants. Analysis of over 14 pairs of age- and sex-matched wild-type and knock-out mice indicated that the articular chondrocyte phenotype in ESET-null mutants is 100% penetrant. Our results demonstrate that expression of ESET plays an essential role in the maintenance of articular cartilage by preventing articular chondrocytes from terminal differentiation and may have implications in joint diseases such as osteoarthritis.

What lies beneath: sub-articular long bone shape scaling in eutherian mammals and saurischian dinosaurs suggests different locomotor adaptations for gigantism.

PubMed

Bonnan, Matthew F; Wilhite, D Ray; Masters, Simon L; Yates, Adam M; Gardner, Christine K; Aguiar, Adam

2013-01-01

Eutherian mammals and saurischian dinosaurs both evolved lineages of huge terrestrial herbivores. Although significantly more saurischian dinosaurs were giants than eutherians, the long bones of both taxa scale similarly and suggest that locomotion was dynamically similar. However, articular cartilage is thin in eutherian mammals but thick in saurischian dinosaurs, differences that could have contributed to, or limited, how frequently gigantism evolved. Therefore, we tested the hypothesis that sub-articular bone, which supports the articular cartilage, changes shape in different ways between terrestrial mammals and dinosaurs with increasing size. Our sample consisted of giant mammal and reptile taxa (i.e., elephants, rhinos, sauropods) plus erect and non-erect outgroups with thin and thick articular cartilage. Our results show that eutherian mammal sub-articular shape becomes narrow with well-defined surface features as size increases. In contrast, this region in saurischian dinosaurs expands and remains gently convex with increasing size. Similar trends were observed in non-erect outgroup taxa (monotremes, alligators), showing that the trends we report are posture-independent. These differences support our hypothesis that sub-articular shape scales differently between eutherian mammals and saurischian dinosaurs. Our results show that articular cartilage thickness and sub-articular shape are correlated. In mammals, joints become ever more congruent and thinner with increasing size, whereas archosaur joints remained both congruent and thick, especially in sauropods. We suggest that gigantism occurs less frequently in mammals, in part, because joints composed of thin articular cartilage can only become so congruent before stress cannot be effectively alleviated. In contrast, frequent gigantism in saurischian dinosaurs may be explained, in part, by joints with thick articular cartilage that can deform across large areas with increasing load.

What Lies Beneath: Sub-Articular Long Bone Shape Scaling in Eutherian Mammals and Saurischian Dinosaurs Suggests Different Locomotor Adaptations for Gigantism

PubMed Central

Bonnan, Matthew F.; Wilhite, D. Ray; Masters, Simon L.; Yates, Adam M.; Gardner, Christine K.; Aguiar, Adam

2013-01-01

Eutherian mammals and saurischian dinosaurs both evolved lineages of huge terrestrial herbivores. Although significantly more saurischian dinosaurs were giants than eutherians, the long bones of both taxa scale similarly and suggest that locomotion was dynamically similar. However, articular cartilage is thin in eutherian mammals but thick in saurischian dinosaurs, differences that could have contributed to, or limited, how frequently gigantism evolved. Therefore, we tested the hypothesis that sub-articular bone, which supports the articular cartilage, changes shape in different ways between terrestrial mammals and dinosaurs with increasing size. Our sample consisted of giant mammal and reptile taxa (i.e., elephants, rhinos, sauropods) plus erect and non-erect outgroups with thin and thick articular cartilage. Our results show that eutherian mammal sub-articular shape becomes narrow with well-defined surface features as size increases. In contrast, this region in saurischian dinosaurs expands and remains gently convex with increasing size. Similar trends were observed in non-erect outgroup taxa (monotremes, alligators), showing that the trends we report are posture-independent. These differences support our hypothesis that sub-articular shape scales differently between eutherian mammals and saurischian dinosaurs. Our results show that articular cartilage thickness and sub-articular shape are correlated. In mammals, joints become ever more congruent and thinner with increasing size, whereas archosaur joints remained both congruent and thick, especially in sauropods. We suggest that gigantism occurs less frequently in mammals, in part, because joints composed of thin articular cartilage can only become so congruent before stress cannot be effectively alleviated. In contrast, frequent gigantism in saurischian dinosaurs may be explained, in part, by joints with thick articular cartilage that can deform across large areas with increasing load. PMID:24130690

Caudal articular process dysplasia of thoracic vertebrae in neurologically normal French bulldogs, English bulldogs, and Pugs: Prevalence and characteristics.

PubMed

Bertram, Simon; Ter Haar, Gert; De Decker, Steven

2018-02-20

The aims of this study were to evaluate the prevalence and anatomical characteristics of thoracic caudal articular process dysplasia in French bulldogs, English bulldogs and Pugs presenting for problems unrelated to spinal disease. In this retrospective cross-sectional study, computed tomography scans of the thoracic vertebral column of these three breeds were reviewed for the presence and location of caudal articular process hypoplasia and aplasia, and compared between breeds. A total of 271 dogs met the inclusion criteria: 108 French bulldogs, 63 English bulldogs, and 100 Pugs. A total of 70.4% of French bulldogs, 84.1% of English bulldogs, and 97.0% of Pugs showed evidence of caudal articular process dysplasia. Compared to French and English bulldogs, Pugs showed a significantly higher prevalence of caudal articular process aplasia, but also a lower prevalence of caudal articular process hypoplasia, a higher number of affected vertebrae per dog and demonstrated a generalized and bilateral spatial pattern more frequently. Furthermore, Pugs showed a significantly different anatomical distribution of caudal articular process dysplasia along the vertebral column, with a high prevalence of caudal articular process aplasia between T10 and T13. This area was almost completely spared in French and English bulldogs. As previously suggested, caudal articular process dysplasia is a common finding in neurologically normal Pugs but this also seems to apply to French and English bulldogs. The predisposition of clinically relevant caudal articular process dysplasia in Pugs is possibly not only caused by the higher prevalence of caudal articular process dysplasia, but also by breed specific anatomical characteristics. © 2018 American College of Veterinary Radiology.

Synergistic effects of intravenous and intra-articular tranexamic acid on reducing hemoglobin loss in revision total knee arthroplasty: a prospective, randomized, controlled study.

PubMed

Yuan, Xiangwei; Wang, Jiaxing; Wang, Qiaojie; Zhang, Xianlong

2018-04-01

Tranexamic acid decreases blood loss in primary total knee arthroplasty, and no related prospective randomized clinical trials have been conducted to evaluate the effectiveness and safety of tranexamic acid in revision total knee arthroplasty. Thus, we conducted this work to evaluate the synergistic effects of intravenous plus intra-articular tranexamic acid on reducing hemoglobin loss compared with intra-articular tranexamic acid alone in revision total knee arthroplasty. This prospective, controlled study randomized 96 patients undergoing revision total knee arthroplasty into two groups: an intravenous plus intra-articular tranexamic acid group (48 patients who received 20 mg/kg intravenous tranexamic acid and 3.0 g intra-articular tranexamic acid); and an intra-articular tranexamic acid alone group (48 patients who received the same intravenous volume of normal saline and 3.0 g intra-articular tranexamic acid). The primary outcome was hemoglobin loss. Secondary outcomes included the volume of drain output, the percentage of patients who received transfusions, the number of units transfused, and thromboembolic events. The baseline data, preoperative hemoglobin, and tourniquet time were similar in both groups. There was significantly less hemoglobin loss in the intravenous plus intra-articular tranexamic acid group compared with the intra-articular tranexamic acid alone group (2.7 ± 0.6 g/dL and 3.7 ± 0.7 g/dL; p < 0.001). Compared with the intra-articular tranexamic acid alone group, the intravenous plus intra-articular tranexamic acid group also had significantly less drain output, fewer patients who received transfusions, and fewer units transfused (all p < 0.05). There were no significant differences in thromboembolic events in the two groups during the 3-month follow-up. Compared with intra-articular tranexamic acid alone, combined intravenous plus intra-articular tranexamic acid significantly reduced hemoglobin loss and the need for transfusion without an apparent increase in thromboembolic events in patients who underwent revision total knee arthroplasty. © 2018 AABB.

Local adherent technique for transplanting mesenchymal stem cells as a potential treatment of cartilage defect.

PubMed

Koga, Hideyuki; Shimaya, Masayuki; Muneta, Takeshi; Nimura, Akimoto; Morito, Toshiyuki; Hayashi, Masaya; Suzuki, Shiro; Ju, Young-Jin; Mochizuki, Tomoyuki; Sekiya, Ichiro

2008-01-01

Current cell therapy for cartilage regeneration requires invasive procedures, periosteal coverage and scaffold use. We have developed a novel transplantation method with synovial mesenchymal stem cells (MSCs) to adhere to the cartilage defect. For ex vivo analysis in rabbits, the cartilage defect was faced upward, filled with synovial MSC suspension, and held stationary for 2.5 to 15 minutes. The number of attached cells was examined. For in vivo analysis in rabbits, an autologous synovial MSC suspension was placed on the cartilage defect, and the position was maintained for 10 minutes to adhere the cells to the defect. For the control, either the same cell suspension was injected intra-articularly or the defects were left empty. The three groups were compared macroscopically and histologically. For ex vivo analysis in humans, in addition to the similar experiment in rabbits, the expression and effects of neutralizing antibodies for adhesion molecules were examined. Ex vivo analysis in rabbits demonstrated that the number of attached cells increased in a time-dependent manner, and more than 60% of cells attached within 10 minutes. The in vivo study showed that a large number of transplanted synovial MSCs attached to the defect at 1 day, and the cartilage defect improved at 24 weeks. The histological score was consistently better than the scores of the two control groups (same cell suspension injected intra-articularly or defects left empty) at 4, 12, and 24 weeks. Ex vivo analysis in humans provided similar results to those in rabbits. Intercellular adhesion molecule 1-positive cells increased between 1 minute and 10 minutes, and neutralizing antibodies for intercellular adhesion molecule 1, vascular cell adhesion molecule 1 and activated leukocyte-cell adhesion molecule inhibited the attachment. Placing MSC suspension on the cartilage defect for 10 minutes resulted in adherence of >60% of synovial MSCs to the defect, and promoted cartilage regeneration. This adherent method makes it possible to adhere MSCs with low invasion, without periosteal coverage, and without a scaffold.

Analgesia after ACL reconstruction: Hamstring donor-site injection versus intra-articular local anaesthetic injection.

PubMed

Sonnery-Cottet, B; Saithna, A; Azeem, A; Choudja, E; Pic, J B; Cabaton, J; Thaunat, M

2017-04-01

The purpose of this study was to compare hamstring donor-site injection versus intra-articular injection of a local anaesthetic for analgesia after anterior cruciate ligament (ACL) reconstruction. The two methods provide similar pain relief. 158 consecutive patients undergoing ACL hamstring tendon graft reconstruction (semi-tendinosus/gracilis [STG] or four-stranded semi-tendinosus [ST4]) during two periods in 2015 were included. Peripheral nerve block was not performed. At the end of surgery, 20mL of ropivacaine 7.5mg/mL was injected, intra-articularly during the early period (n=79) and into the hamstring donor site during the second period (n=79). Post-operative pain was evaluated subjectively by the patients using a visual analogue scale (VAS). We recorded patient demographics, concomitant surgical procedures, VAS pain scores, rescue analgesic use, time to discharge, and patient satisfaction. VAS pain score, side effects, and patient satisfaction were also recorded during a phone interview on the day after surgery (D1). Mean VAS pain scores were not significantly different between the two groups immediately after surgery (D0) or on D1 (D0: intra-articular, 2.08 and donor site, 1.88; Mann-Whitney P=0.6). Neither were the groups significantly different for rescue analgesic use, patient satisfaction, or quadriceps activation. The same local anaesthetic provides similar pain relief when injected intra-articularly or into the hamstring donor site after hamstring tendon ACL reconstruction (STG or ST4). III, prospective case-control study. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Chronic In Vivo Load Alteration Induces Degenerative Changes in the Rat Tibiofemoral Joint

PubMed Central

Roemhildt, M. L.; Beynnon, B. D.; Gauthier, A. E.; Gardner-Morse, M.; Ertem, F.; Badger, G. J.

2012-01-01

Objective We investigated the relationship between the magnitude and duration of sustained compressive load alteration and the development of degenerative changes in the rat tibiofemoral joint. Methods A varus loading device was attached to the left hind limb of mature rats to apply increased compression to the medial compartment and decreased compression to the lateral compartment of the tibiofemoral joint of either 0% or 100% body weight for 0, 6 or 20 weeks. Compartment-specific assessment of the tibial plateaus included biomechanical measures (articular cartilage aggregate modulus, permeability and Poisson’s ratio, and subchondral bone modulus) and histological assessments (articular cartilage, calcified cartilage, and subchondral bone thicknesses, degenerative scoring parameters, and articular cartilage cellularity). Results Increased compression in the medial compartment produced significant degenerative changes consistent with the development of osteoarthritis including a progressive decrease in cartilage aggregate modulus (43% and 77% at 6 and 20 weeks), diminished cellularity (38% and 51% at 6 and 20 weeks), and increased histological degeneration. At 20 weeks, medial compartment articular cartilage thickness deceased 30% while subchondral bone thickness increased 32% and subchondral bone modulus increased 99%. Decreased compression in the lateral compartment increased calcified cartilage thickness, diminished region-specific subchondral bone thickness and revealed trends for reduced cellularity and decreased articular cartilage thickness at 20 weeks. Conclusions Altered chronic joint loading produced degenerative changes consistent with those observed clinically with the development of osteoarthritis and may replicate the slow development of non-traumatic osteoarthritis in which mechanical loads play a primary etiological role. PMID:23123358

Oral administration of undenatured native chicken type II collagen (UC-II) diminished deterioration of articular cartilage in a rat model of osteoarthritis (OA).

PubMed

Bagi, C M; Berryman, E R; Teo, S; Lane, N E

2017-12-01

The aim of this study was to determine the ability of undenatured native chicken type II collagen (UC-II) to prevent excessive articular cartilage deterioration in a rat model of osteoarthritis (OA). Twenty male rats were subjected to partial medial meniscectomy tear (PMMT) surgery to induce OA. Immediately after the surgery 10 rats received vehicle and another 10 rats oral daily dose of UC-II at 0.66 mg/kg for a period of 8 weeks. In addition 10 naïve rats were used as an intact control and another 10 rats received sham surgery. Study endpoints included a weight-bearing capacity of front and hind legs, serum biomarkers of bone and cartilage metabolism, analyses of subchondral and cancellous bone at the tibial epiphysis and metaphysis, and cartilage pathology at the medial tibial plateau using histological methods. PMMT surgery produced moderate OA at the medial tibial plateau. Specifically, the deterioration of articular cartilage negatively impacted the weight bearing capacity of the operated limb. Immediate treatment with the UC-II preserved the weight-bearing capacity of the injured leg, preserved integrity of the cancellous bone at tibial metaphysis and limited the excessive osteophyte formation and deterioration of articular cartilage. Study results demonstrate that a clinically relevant daily dose of UC-II when applied immediately after injury can improve the mechanical function of the injured knee and prevent excessive deterioration of articular cartilage. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Development of a Novel Large Animal Model to Evaluate Human Dental Pulp Stem Cells for Articular Cartilage Treatment.

PubMed

Fernandes, Tiago Lazzaretti; Shimomura, Kazunori; Asperti, Andre; Pinheiro, Carla Cristina Gomes; Caetano, Heloísa Vasconcellos Amaral; Oliveira, Claudia Regina G C M; Nakamura, Norimasa; Hernandez, Arnaldo José; Bueno, Daniela Franco

2018-05-04

Chondral lesion is a pathology with high prevalence, reaching as much as 63% of general population and 36% among athletes. The ability of human Dental Pulp Stem Cells (DPSCs) to differentiate into chondroblasts in vitro suggests that this stem cell type may be useful for tissue bioengineering. However, we have yet to identify a study of large animal models in which DPSCs were used to repair articular cartilage. Therefore, this study aimed to describe a novel treatment for cartilage lesion with DPSCs on a large animal model. Mesenchymal stem cells (MSC) were obtained from deciduous teeth and characterized by flow cytometry. DPSCs were cultured and added to a collagen type I/III biomaterial composite scaffold. Brazilian miniature pig (BR-1) was used. A 6-mm diameter, full-thickness chondral defect was created in each posterior medial condyle. The defects were covered with scaffold alone or scaffold + DPSCs on the contralateral side. Animals were euthanized 6 weeks post-surgery. Cartilage defects were analyzed macroscopically and histology according to modified O'Driscoll scoring system. Flow cytometry confirmed characterization of DPSCs as MSCs. Macroscopic and histological findings suggested that this time period was reasonable for evaluating cartilage repair. To our knowledge, this study provides the first description of an animal model using DPSCs to study the differentiation of hyaline articular cartilage in vivo. The animals tolerated the procedure well and did not show clinical or histological rejection of the DPSCs, reinforcing the feasibility of this descriptive miniature pig model for pre-clinical studies.

Cartilage constructs engineered from chondrocytes overexpressing IGF-I improve the repair of osteochondral defects in a rabbit model.

PubMed

Madry, H; Kaul, G; Zurakowski, D; Vunjak-Novakovic, G; Cucchiarini, M

2013-04-16

Tissue engineering combined with gene therapy is a promising approach for promoting articular cartilage repair. Here, we tested the hypothesis that engineered cartilage with chondrocytes overexpressing a human insulin-like growth factor I (IGF-I) gene can enhance the repair of osteochondral defects, in a manner dependent on the duration of cultivation. Genetically modified chondrocytes were cultured on biodegradable polyglycolic acid scaffolds in dynamic flow rotating bioreactors for either 10 or 28 d. The resulting cartilaginous constructs were implanted into osteochondral defects in rabbit knee joints. After 28 weeks of in vivo implantation, immunoreactivity to ß-gal was detectable in the repair tissue of defects that received lacZ constructs. Engineered cartilaginous constructs based on IGF-I-overexpressing chondrocytes markedly improved osteochondral repair compared with control (lacZ) constructs. Moreover, IGF-I constructs cultivated for 28 d in vitro significantly promoted osteochondral repair vis-à-vis similar constructs cultivated for 10 d, leading to significantly decreased osteoarthritic changes in the cartilage adjacent to the defects. Hence, the combination of spatially defined overexpression of human IGF-I within a tissue-engineered construct and prolonged bioreactor cultivation resulted in most enhanced articular cartilage repair and reduction of osteoarthritic changes in the cartilage adjacent to the defect. Such genetically enhanced tissue engineering provides a versatile tool to evaluate potential therapeutic genes in vivo and to improve our comprehension of the development of the repair tissue within articular cartilage defects. Insights gained with additional exploration using this model may lead to more effective treatment options for acute cartilage defects.

CARTILAGE CONSTRUCTS ENGINEERED FROM CHONDROCYTES OVEREXPRESSING IGF-I IMPROVE THE REPAIR OF OSTEOCHONDRAL DEFECTS IN A RABBIT MODEL

PubMed Central

Madry, Henning; Kaul, Gunter; Zurakowski, David; Vunjak-Novakovic, Gordana; Cucchiarini, Magali

2015-01-01

Tissue engineering combined with gene therapy is a promising approach for promoting articular cartilage repair. Here, we tested the hypothesis that engineered cartilage with chondrocytes over expressing a human insulin-like growth factor I (IGF-I) gene can enhance the repair of osteochondral defects, in a manner dependent on the duration of cultivation. Genetically modified chondrocytes were cultured on biodegradable polyglycolic acid scaffolds in dynamic flow rotating bioreactors for either 10 or 28 d. The resulting cartilaginous constructs were implanted into osteochondral defects in rabbit knee joints. After 28 weeks of in vivo implantation, immunoreactivity to ß-gal was detectable in the repair tissue of defects that received lacZ constructs. Engineered cartilaginous constructs based on IGF-I-over expressing chondrocytes markedly improved osteochondral repair compared with control (lacZ) constructs. Moreover, IGF-I constructs cultivated for 28 d in vitro significantly promoted osteochondral repair vis-à-vis similar constructs cultivated for 10 d, leading to significantly decreased osteoarthritic changes in the cartilage adjacent to the defects. Hence, the combination of spatially defined overexpression of human IGF-I within a tissue-engineered construct and prolonged bioreactor cultivation resulted in most enhanced articular cartilage repair and reduction of osteoarthritic changes in the cartilage adjacent to the defect. Such genetically enhanced tissue engineering provides a versatile tool to evaluate potential therapeutic genes in vivo and to improve our comprehension of the development of the repair tissue within articular cartilage defects. Insights gained with additional exploration using this model may lead to more effective treatment options for acute cartilage defects. PMID:23588785

Developmentally inspired programming of adult human mesenchymal stromal cells toward stable chondrogenesis.

PubMed

Occhetta, Paola; Pigeot, Sebastien; Rasponi, Marco; Dasen, Boris; Mehrkens, Arne; Ullrich, Thomas; Kramer, Ina; Guth-Gundel, Sabine; Barbero, Andrea; Martin, Ivan

2018-05-01

It is generally accepted that adult human bone marrow-derived mesenchymal stromal cells (hMSCs) are default committed toward osteogenesis. Even when induced to chondrogenesis, hMSCs typically form hypertrophic cartilage that undergoes endochondral ossification. Because embryonic mesenchyme is obviously competent to generate phenotypically stable cartilage, it is questioned whether there is a correspondence between mesenchymal progenitor compartments during development and in adulthood. Here we tested whether forcing specific early events of articular cartilage development can program hMSC fate toward stable chondrogenesis. Inspired by recent findings that spatial restriction of bone morphogenetic protein (BMP) signaling guides embryonic progenitors toward articular cartilage formation, we hypothesized that selective inhibition of BMP drives the phenotypic stability of hMSC-derived chondrocytes. Two BMP type I receptor-biased kinase inhibitors were screened in a microfluidic platform for their time- and dose-dependent effect on hMSC chondrogenesis. The different receptor selectivity profile of tested compounds allowed demonstration that transient blockade of both ALK2 and ALK3 receptors, while permissive to hMSC cartilage formation, is necessary and sufficient to maintain a stable chondrocyte phenotype. Remarkably, even upon compound removal, hMSCs were no longer competent to undergo hypertrophy in vitro and endochondral ossification in vivo, indicating the onset of a constitutive change. Our findings demonstrate that adult hMSCs effectively share properties of embryonic mesenchyme in the formation of transient but also of stable cartilage. This opens potential pharmacological strategies to articular cartilage regeneration and more broadly indicates the relevance of developmentally inspired protocols to control the fate of adult progenitor cell systems.

Co-Expression and Co-Localization of Cartilage Glycoproteins CHI3L1 and Lubricin in Osteoarthritic Cartilage: Morphological, Immunohistochemical and Gene Expression Profiles

PubMed Central

Szychlinska, Marta Anna; Trovato, Francesca Maria; Di Rosa, Michelino; Malaguarnera, Lucia; Puzzo, Lidia; Leonardi, Rosy; Castrogiovanni, Paola; Musumeci, Giuseppe

2016-01-01

Osteoarthritis is the most common human arthritis characterized by degeneration of articular cartilage. Several studies reported that levels of human cartilage glycoprotein chitinase 3-like-1 (CHI3L1) are known as a potential marker for the activation of chondrocytes and the progression of Osteoarthritis (OA), whereas lubricin appears to be chondroprotective. The aim of this study was to investigate the co-expression and co-localization of CHI3L1 and lubricin in normal and osteoarthritic rat articular cartilage to correlate their modified expression to a specific grade of OA. Samples of normal and osteoarthritic rat articular cartilage were analyzed by the Kellgren–Lawrence OA severity scores, the Kraus’ modified Mankin score and the Histopathology Osteoarthritis Research Society International (OARSI) system for histomorphometric evaluations, and through CHI3L1 and lubricin gene expression, immunohistochemistry and double immuno-staining analysis. The immunoexpression and the mRNA levels of lubricin increased in normal cartilage and decreased in OA cartilage (normal vs. OA, p < 0.01). By contrast, the immunoexpression and the mRNA levels of CHI3L1 increased in OA cartilage and decreased in normal cartilage (normal vs. OA, p < 0.01). Our findings are consistent with reports suggesting that these two glycoproteins are functionally associated with the development of OA and in particular with grade 2/3 of OA, suggesting that in the future they could be helpful to stage the severity and progression of the disease. PMID:26978347

Radiographic Outcomes of Volar Locked Plating for Distal Radius Fractures

PubMed Central

Mignemi, Megan E.; Byram, Ian R.; Wolfe, Carmen C.; Fan, Kang-Hsien; Koehler, Elizabeth A.; Block, John J.; Jordanov, Martin I.; Watson, Jeffry T.; Weikert, Douglas R.; Lee, Donald H.

2013-01-01

Purpose To assess the ability of volar locked plating to achieve and maintain normal radiographic parameters for articular stepoff, volar tilt, radial inclination, ulnar variance, and radial height in distal radius fractures. Methods We performed a retrospective review of 185 distal radius fractures that underwent volar locked plating with a single plate design over a 5-year period. We reviewed radiographs and recorded measurements for volar tilt, radial inclination, ulnar variance, radial height, and articular stepoff. We used logistic regression to determine the association between return to radiographic standard norms and fracture type. Results At the first and final postoperative follow-up visits, we observed articular congruence less than 2 mm in 92% of fractures at both times. Normal volar tilt (11°) was restored in 46% at the first follow-up and 48% at the final one. Radial inclination (22°) was achieved in 44% at the first follow-up and 43% at the final one, and ulnar variance (01 ± 2 mm) was achieved in 53% at the first follow-up and 53% at the final one. In addition, radial height (14 ± 1mm) was restored in 14% at the first follow-up and 12% at the final one. More complex, intra-articular fractures (AO class B and C and Frykman types 3, 4, 7, and 8) were less likely to be restored to normal radiographic parameters. However, because of the small sample size for some fracture types, it was difficult to discover significant associations between fracture type and radiographic outcome. Conclusions Volar locked plating for distal radius fractures achieved articular stepoff less than 2 mm in most fractures but only restored and maintained normal radiographic measurements for volar tilt, radial inclination, and ulnar variance in 50% of fractures. The ability of volar locked plating to restore and maintain ulnar variance and volar tilt decreased with more complex intra-articular fracture types. PMID:23218558

Practical approach to hip pain.

PubMed

Karrasch, Christopher; Lynch, Scott

2014-07-01

Hip pain is a common complaint among patients presenting to outpatient clinics. Stratifying patients based on age, acuity, and location of pain (extra-articular vs intra-articular) can help to aid in appropriate imaging and timely referral to an orthopedic surgeon. A thorough history and an organized physical examination combined with radiographs are usually sufficient to diagnose most hip complaints. If the diagnosis remains uncertain, magnetic resonance imaging, usually with intra-articular gadolinium, is the imaging modality of choice in diagnosing both intra-articular and extra-articular pathologies. Copyright © 2014 Elsevier Inc. All rights reserved.

Extra-articular hip impingement: a narrative review of the literature

PubMed Central

Cheatham, Scott W.

2016-01-01

There is growing subgroup of patients with poor outcomes after hip arthroscopy for intra-articular pathology suggesting unrecognized cause(s) of impingement may exist. Extra-articular hip impingement (EHI) is an emerging group of conditions that have been associated with intra-articular causes of impingement and may be an unrecognized source of pain. EHI is caused by abnormal contact between the extra-articular regions of the proximal femur and pelvis. This review discusses the most common forms for EHI including: central iliopsoas impingement, subspine impingement, ischiofemoral impingement, and greater trochanteric-pelvic impingement. The clinical presentation of each pathology will be discussed since EHI conditions share similar clinical features as the intra-articular pathology but also contain some unique characteristics. PMID:27069266

Solute transport across the articular surface of injured cartilage.

PubMed

Chin, Hooi Chuan; Moeini, Mohammad; Quinn, Thomas M

2013-07-15

Solute transport through extracellular matrix (ECM) is important to physiology and contrast agent-based clinical imaging of articular cartilage. Mechanical injury is likely to have important effects on solute transport since it involves alteration of ECM structure. Therefore it is of interest to characterize effects of mechanical injury on solute transport in cartilage. Using cartilage explants injured by an established mechanical compression protocol, effective partition coefficients and diffusivities of solutes for transport across the articular surface were measured. A range of fluorescent solutes (fluorescein isothiocyanate, 4 and 40kDa dextrans, insulin, and chondroitin sulfate) and an X-ray contrast agent (sodium iodide) were used. Mechanical injury was associated with a significant increase in effective diffusivity versus uninjured explants for all solutes studied. On the other hand, mechanical injury had no effects on effective partition coefficients for most solutes tested, except for 40kDa dextran and chondroitin sulfate where small but significant changes in effective partition coefficient were observed in injured explants. Findings highlight enhanced diffusive transport across the articular surface of injured cartilage, which may have important implications for injury and repair situations. Results also support development of non-equilibrium methods for identification of focal cartilage lesions by contrast agent-based clinical imaging. Copyright © 2013 Elsevier Inc. All rights reserved.

Low-field one-dimensional and direction-dependent relaxation imaging of bovine articular cartilage

NASA Astrophysics Data System (ADS)

Rössler, Erik; Mattea, Carlos; Mollova, Ayret; Stapf, Siegfried

2011-12-01

The structure of articular cartilage is separated into three layers of differently oriented collagen fibers, which is accompanied by a gradient of increasing glycosaminoglycan (GAG) and decreasing water concentration from the top layer towards the bone interface. The combined effect of these structural variations results in a change of the longitudinal and transverse relaxation times as a function of the distance from the cartilage surface. In this paper, this dependence is investigated at a magnetic field strength of 0.27 T with a one-dimensional depth resolution of 50 μm on bovine hip and stifle joint articular cartilage. By employing this method, advantage is taken of the increasing contrast of the longitudinal relaxation rate found at lower magnetic field strengths. Furthermore, evidence for an orientational dependence of relaxation times with respect to an axis normal to the surface plane is given, an observation that has recently been reported using high-field MRI and that was explained by preferential orientations of collagen bundles in each of the three cartilage zones. In order to quantify the extent of a further contrast mechanism and to estimate spatially dependent glycosaminoglycan concentrations, the data are supplemented by proton relaxation times that were acquired in bovine articular cartilage that was soaked in a 0.8 mM aqueous Gd ++ solution.

Kirschner-wire fixation for postburn flexion contracture deformity and consequences on articular surface.

PubMed

Sungur, Nezih; Ulusoy, Mustafa Gürhan; Boyacgil, Süreyya; Ortaparmak, Hülya; Akyüz, Mihriban; Ortak, Turgut; Koçer, Uğur; Sensöz, Omer

2006-02-01

Kirschner-wire (K-wire) fixation for 3-6 weeks is an approved method for stabilization of the fingers after the release of flexion contracture deformity. On the other hand, articular surface damage in small joints due to pin fixation is still a topic of debate. Reports claiming permanent joint destruction due to this procedure exist in the literature. To clarify this doubt, a prospective study was carried out in 72 patients with flexion contracture of the hand fingers. After the surgical release of the deformity, immobilization of the interphalangeal (IP) and metacarpophalangeal (MCP) joints was carried out with K-wire fixation for 3 weeks. Clinical evaluation of the patients was accomplished with total active motion (TAM), grip, and pinch force measurements, whereas magnetic resonance (MR) and radionuclide imaging were used as radiodiagnostic tools. Mean follow-up period of the patients was 32 months. Satisfactory results were obtained in terms of functional and esthetic aspects. Evaluation of the data derived from the clinical and radiologic measurements revealed no permanent articular surface damage. K-wire fixation was documented to be an invaluable therapeutic approach not only to prevent recurrence of the contracture deformity but also to stabilize the skin graft effectively. This technique was concluded to provide effective immobilization without permanent articular damage.

Total-Body Irradiation Produces Late Degenerative Joint Damage in Rats

PubMed Central

Hutchinson, Ian D.; Olson, John; Lindburg, Carl A.; Payne, Valerie; Collins, Boyce; Smith, Thomas L.; Munley, Michael T.; Wheeler, Kenneth T.; Willey, Jeffrey S.

2014-01-01

Purpose Premature musculoskeletal joint failure is a major source of morbidity among childhood cancer survivors. Radiation effects on synovial joint tissues of the skeleton are poorly understood. Our goal was to assess long-term changes in the knee joint from skeletally mature rats that received total-body irradiation while skeletal growth was ongoing. Materials and Methods 14 week-old rats were irradiated with 1, 3 or 7 Gy total-body doses of 18 MV x-rays. At 53 weeks of age, structural and compositional changes in knee joint tissues (articular cartilage, subchondral bone, and trabecular bone) were characterized using 7T MRI, nanocomputed tomography (nanoCT), microcomputed tomography (microCT), and histology. Results T2 relaxation times of the articular cartilage were lower after exposure to all doses. Likewise, calcifications were observed in the articular cartilage. Trabecular bone microarchitecture was compromised in the tibial metaphysis at 7 Gy. Mild to moderate cartilage erosion was scored in the 3 and 7 Gy rats. Conclusions Late degenerative changes in articular cartilage and bone were observed after total body irradiation in adult rats exposed prior to skeletal maturity. 7T MRI, microCT, nanoCT, and histology identified potential prognostic indicators of late radiation-induced joint damage. PMID:24885745

Physiological loading of joints prevents cartilage degradation through CITED2

PubMed Central

Leong, Daniel J.; Li, Yong H.; Gu, Xiang I.; Sun, Li; Zhou, Zuping; Nasser, Philip; Laudier, Damien M.; Iqbal, Jameel; Majeska, Robert J.; Schaffler, Mitchell B.; Goldring, Mary B.; Cardoso, Luis; Zaidi, Mone; Sun, Hui B.

2011-01-01

Both overuse and disuse of joints up-regulate matrix metalloproteinases (MMPs) in articular cartilage and cause tissue degradation; however, moderate (physiological) loading maintains cartilage integrity. Here, we test whether CBP/p300-interacting transactivator with ED-rich tail 2 (CITED2), a mechanosensitive transcriptional coregulator, mediates this chondroprotective effect of moderate mechanical loading. In vivo, hind-limb immobilization of Sprague-Dawley rats up-regulates MMP-1 and causes rapid, histologically detectable articular cartilage degradation. One hour of daily passive joint motion prevents these changes and up-regulates articular cartilage CITED2. In vitro, moderate (2.5 MPa, 1 Hz) intermittent hydrostatic pressure (IHP) treatment suppresses basal MMP-1 expression and up-regulates CITED2 in human chondrocytes, whereas high IHP (10 MPa) down-regulates CITED2 and increases MMP-1. Competitive binding and transcription assays demonstrate that CITED2 suppresses MMP-1 expression by competing with MMP transactivator, Ets-1 for its coactivator p300. Furthermore, CITED2 up-regulation in vitro requires the p38δ isoform, which is specifically phosphorylated by moderate IHP. Together, these studies identify a novel regulatory pathway involving CITED2 and p38δ, which may be critical for the maintenance of articular cartilage integrity under normal physical activity levels.—Leong, D. J., Li, Y. H., Gu, X. I., Sun, L., Zhou, Z., Nasser, P., Laudier, D. M., Iqbal, J., Majeska, R. J., Schaffler, M. B., Goldring, M. B., Cardoso, L., Zaidi, M., Sun, H. B. Physiological loading of joints prevents cartilage degradation through CITED2. PMID:20826544

On fragmenting, densely mineralised acellular protrusions into articular cartilage and their possible role in osteoarthritis

PubMed Central

Boyde, A; Davis, G R; Mills, D; Zikmund, T; Cox, T M; Adams, V L; Niker, A; Wilson, P J; Dillon, J P; Ranganath, L R; Jeffery, N; Jarvis, J C; Gallagher, J A

2014-01-01

High density mineralised protrusions (HDMP) from the tidemark mineralising front into hyaline articular cartilage (HAC) were first described in Thoroughbred racehorse fetlock joints and later in Icelandic horse hock joints. We now report them in human material. Whole femoral heads removed at operation for joint replacement or from dissection room cadavers were imaged using magnetic resonance imaging (MRI) dual echo steady state at 0.23 mm resolution, then 26-μm resolution high contrast X-ray microtomography, sectioned and embedded in polymethylmethacrylate, blocks cut and polished and re-imaged with 6-μm resolution X-ray microtomography. Tissue mineralisation density was imaged using backscattered electron SEM (BSE SEM) at 20 kV with uncoated samples. HAC histology was studied by BSE SEM after staining block faces with ammonium triiodide solution. HDMP arise via the extrusion of an unknown mineralisable matrix into clefts in HAC, a process of acellular dystrophic calcification. Their formation may be an extension of a crack self-healing mechanism found in bone and articular calcified cartilage. Mineral concentration exceeds that of articular calcified cartilage and is not uniform. It is probable that they have not been reported previously because they are removed by decalcification with standard protocols. Mineral phase morphology frequently shows the agglomeration of many fine particles into larger concretions. HDMP are surrounded by HAC, are brittle, and show fault lines within them. Dense fragments found within damaged HAC could make a significant contribution to joint destruction. At least larger HDMP can be detected with the best MRI imaging ex vivo. PMID:25132002

The Roles of Mechanical Stresses in the Pathogenesis of Osteoarthritis

PubMed Central

Anderson, Donald D.; Brown, Thomas D.; Tochigi, Yuki; Martin, James A.

2013-01-01

Excessive joint surface loadings, either single (acute impact event) or repetitive (cumulative contact stress), can cause the clinical syndrome of osteoarthritis (OA). Despite advances in treatment of injured joints, the risk of OA following joint injuries has not decreased in the past 50 years. Cumulative excessive articular surface contact stress that leads to OA results from posttraumatic joint incongruity and instability, and joint dysplasia, but may also cause OA in patients without known joint abnormalities. In vitro investigations show that excessive articular cartilage loading triggers release of reactive oxygen species (ROS) from mitochondria, and that these ROS cause chondrocyte death and matrix degradation. Preventing release of ROS or inhibiting their effects preserves chondrocytes and their matrix. Fibronectin fragments released from articular cartilage subjected to excessive loads also stimulate matrix degradation; inhibition of molecular pathways initiated by these fragments prevents this effect. Additionally, injured chondrocytes release alarmins that activate chondroprogentior cells in vitro that propogate and migrate to regions of damaged cartilage. These cells also release chemokines and cytokines that may contribute to inflammation that causes progressive cartilage loss. Distraction and motion of osteoarthritic human ankles can promote joint remodeling, decrease pain, and improve joint function in patients with end-stage posttraumatic OA. These advances in understanding of how altering mechanical stresses can lead to remodeling of osteoarthritic joints and how excessive stress causes loss of articular cartilage, including identification of mechanically induced mediators of cartilage loss, provide the basis for new biologic and mechanical approaches to the prevention and treatment of OA. PMID:25067995

Progressive cell-mediated changes in articular cartilage and bone in mice are initiated by a single session of controlled cyclic compressive loading

PubMed Central

Ko, Frank C.; Dragomir, Cecilia L.; Plumb, Darren A.; Hsia, Allison W.; Adebayo, Olufunmilayo O.; Goldring, Steven R.; Wright, Timothy M.; Goldring, Mary B.; van der Meulen, Marjolein C.H.

2017-01-01

We previously showed that repetitive cyclic loading of the mouse knee joint causes changes that recapitulate the features of osteoarthritis (OA) in humans. By applying a single loading session, we characterized the temporal progression of the structural and compositional changes in subchondral bone and articular cartilage. We applied loading during a single 5-minute session to the left tibia of adult (26-week-old) C57Bl/6 male mice at a peak load of 9.0N for 1200 cycles. Knee joints were collected at times 0, 1, and 2 weeks after loading. The changes in articular cartilage and subchondral bone were analyzed by histology, immunohistochemistry (caspase-3 and cathepsin K), and microcomputed tomography. At time 0, no change was evident in chondrocyte viability or cartilage or subchondral bone integrity. However, cartilage pathology demonstrated by localized thinning and proteoglycan loss occurred at 1 and 2 weeks after the single session of loading. Transient cancellous bone loss was evident at 1 week, associated with increased osteoclast number. Bone loss was reversed to control levels at 2 weeks. We observed formation of fibrous and cartilaginous tissues at the joint margins at 1 and 2 weeks. Our findings demonstrate that a single session of noninvasive loading leads to the development of OA-like morphological and cellular alterations in articular cartilage and subchondral bone. The loss in subchondral trabecular bone mass and thickness returns to control levels at 2 weeks, whereas the cartilage thinning and proteoglycan loss persist. PMID:26896841

Lumbar facet anatomy changes in spondylolysis: a comparative skeletal study.

PubMed

Masharawi, Youssef; Dar, Gali; Peleg, Smadar; Steinberg, Nili; Alperovitch-Najenson, Dvora; Salame, Khalil; Hershkovitz, Israel

2007-07-01

Opinions differ as to the exact mechanism responsible for spondylolysis (SP) and whether individuals with specific morphological characteristics of the lumbar vertebral neural arch are predisposed to SP. The aim of our study was to reveal the association between SP and the architecture of lumbar articular facets and the inter-facet region. Using a Microscribe three-dimensional apparatus (Immersion Co., San Jose, CA, USA), length, width and depth of all articular facets and all inter-facet distances in the lumbar spine (L1-L5) were measured. From the Hamann-Todd Human Osteological Collection (Cleveland Museum of Natural History, OH, USA) 120 normal male skeletons with lumbar spines in the control group and 115 with bilateral SP at L5 were selected. Analysis of variance was employed to examine the differences between spondylolytic and normal spines. Three profound differences between SP and the norm appeared: (1) in individuals with SP, the size and shape of L4's neural arch had significantly greater inter-facet widths, significantly shorter inter-facet heights and significantly shorter and narrower articular facets; (2) only in the L4 vertebra in individuals with SP was the inferior inter-facet width greater in size than the superior inter-facet width of the vertebra below (L5) (38.7 mm versus 40 mm); (3) in all lumbar vertebrae, the right inferior articular facets in individuals with SP were flatter compared to the control group. Individuals with L4 "SP" characteristics are at a greater risk of developing fatigue fractures in the form of spondylolysis at L5.

Intramedullary Percutaneous Fixation of Extra-Articular Proximal and Middle Phalanx Fractures.

PubMed

Jovanovic, Nebojsa; Aldlyami, Ehab; Saraj, Basem; Fm Seidam, Mohamed; Badawi, Hamed; Shaat, Ahmed; Alawadi, Khalid; Dodakundi, Chaitanya

2018-06-01

Multiple methods have been described for treating unstable proximal and middle phalangeal fractures. Irrespective of using an open or closed technique of fixation, stiffness and extensor lag at the proximal/distal interphalangeal joint almost always occur. This issue can be avoided by allowing the patients to mobilize the fingers out of plaster or splint as early as possible from the day of surgery. We describe a technique of intramedullary percutaneous fixation of extra-articular proximal and middle phalanx fractures allowing immediate mobilization of fingers, concurrent stabilization with progressive healing and thus preventing such complications.

Factors determining the level and changes in intra-articular pressure in the knee joint of the dog.

PubMed Central

Nade, S; Newbold, P J

1983-01-01

Intra-articular pressure levels were determined for joint positions throughout the normal physiological range of movement of dogs' knee joints. Change in joint position resulted in change in intra-articular pressure. It was demonstrated that intra-articular pressure is highest with the joint in the fully flexed position. Minimum pressure was recorded at a position between 80 degrees and 120 degrees. Minimum pressures were usually subatmospheric. The rate of change of joint position affected intra-articular pressure. The relationship of intra-articular pressure and joint position before and after full flexion demonstrated a hysteresis effect; the pressures were lower than for the same joint position before flexion. Maintenance of the joint in the fully flexed position for increasing periods of time between repeated movement cycles resulted in a similar reduction, of constant magnitude, in pressure between joint positions before and after each period of flexion. However, there was also a progressive decrease in pressure for all joint angles over the total number of movement cycles. There is a contribution to intra-articular pressure of joint capsular compliance and fluid movement into and out of the joint (both of which are time-dependent). The recording of intra-articular pressure in conscious, upright dogs revealed similar pressure levels to those measured in anaesthetized supine dogs. The major determinants of intra-articular pressure in normal dog knee joints include joint size, synovial fluid volume, position of joint, peri-articular tissue and joint anatomy, membrane permeability, capsular compliance, and movement of fluid into and out of the joint. Images Fig. 1 PMID:6875957

Congenital axis dysmorphism in a medieval skeleton : …secunda a vertendo epistropheus….

PubMed

Travan, Luciana; Saccheri, Paola; Toso, Francesco; Crivellato, Enrico

2013-05-01

We describe here the axis dysmorphism that we observed in the skeletal remains of a human child dug up from a fifteenth century cemetery located in north-eastern Italy. This bone defect is discussed in the light of pertinent literature. We performed macroscopical examination and CT scan analysis of the axis. Axis structure was remarkably asymmetric. Whilst the left half exhibited normal morphology, the right one was smaller than normal, and its lateral articular surface showed horizontal orientation. In addition, the odontoid process appeared leftward deviated and displayed a supplementary articular-like facet situated on the right side of its surface. These findings suggest a diagnosis of unilateral irregular segmentation of atlas and axis, a rare dysmorphism dependent upon disturbances of notochordal development in early embryonic life. Likewise other malformations of the craniovertebral junction, this axis defect may alter the delicate mechanisms of upper neck movements and cause a complex series of clinical symptoms. This is an emblematic case whereby human skeletal remains may provide valuable information on the anatomical defects of craniovertebral junction.

Magnetic resonance imaging of the long head of the biceps tendon: benefit of coplanar image.

PubMed

Lin, Anderson; Ting, Julius; Lee, Kwo-Whei

2007-01-01

To evaluate coplanar imaging of the long head of the biceps tendon. We retrospectively compared coronal oblique magnetic resonance images aligned with the principal supraspinatus tendon and with the intra-articular biceps tendon in 21 patients. Magnetic resonance images were analyzed for lesions depicted, including superior labral anteroposterior (SLAP) tears. Arthroscopic findings were reviewed. Coronal oblique images aligned with intra-articular biceps tendon depicted 18 (86%) of 21 coplanar intra-articular biceps tendons. Coplanar images identified 6 cases of tendinosis, 1 tear, 3 intra-articular ruptures, and 20 (95.2%) of 21 exact origins of the tendon. Arthroscopy revealed 18 SLAP tears. The detection of SLAP lesions between both coronal oblique magnetic resonance images was significantly different (P = 0.007). Advantages included imaging of the intra-articular biceps tendon with least partial-volume effects, definition of SLAP lesions and the tendinous origin at the supraglenoid tubercle, depiction of intra-articular bicipital ruptures, and increased sensitivity and specificity for intra-articular lesions.

Assessment of Biomarkers Associated with Joint Injury and Subsequent Post-Traumatic Arthritis

DTIC Science & Technology

2014-10-01

histological assessment. Subchondral bone thickening was significantly increased in the C57BL/6 mice compared to the MRL/MpJ mice in the medial femur (p...human knee following articular injury. Biomarkers will be correlated to joint pathology that will be assessed from microCT and histology . The human...fracturing, sacrificing, and collection of biosamples. MicroCT and histologic analyses have also been completed for the short-term cohort. We have

Conditioned medium as a strategy for human stem cells chondrogenic differentiation.

PubMed

Alves da Silva, M L; Costa-Pinto, A R; Martins, A; Correlo, V M; Sol, P; Bhattacharya, M; Faria, S; Reis, R L; Neves, Nuno M

2015-06-01

Paracrine signalling from chondrocytes has been reported to increase the synthesis and expression of cartilage extracellular matrix (ECM) by stem cells. The use of conditioned medium obtained from chondrocytes for stimulating stem cells chondrogenic differentiation may be a very interesting alternative for moving into the clinical application of these cells, as chondrocytes could be partially replaced by stem cells for this type of application. In the present study we aimed to achieve chondrogenic differentiation of two different sources of stem cells using conditioned medium, without adding growth factors. We tested both human bone marrow-derived mesenchymal stem cells (hBSMCs) and human Wharton's jelly-derived stem cells (hWJSCs). Conditioned medium obtained from a culture of human articular chondrocytes was used to feed the cells during the experiment. Cultures were performed in previously produced three-dimensional (3D) scaffolds, composed of a blend of 50:50 chitosan:poly(butylene succinate). Both types of stem cells were able to undergo chondrogenic differentiation without the addition of growth factors. Cultures using hWJSCs showed significantly higher GAGs accumulation and expression of cartilage-related genes (aggrecan, Sox9 and collagen type II) when compared to hBMSCs cultures. Conditioned medium obtained from articular chondrocytes induced the chondrogenic differentiation of MSCs and ECM formation. Obtained results showed that this new strategy is very interesting and should be further explored for clinical applications. Copyright © 2013 John Wiley & Sons, Ltd.

Ultrasound guided intra-articular ketorolac versus corticosteroid injection in osteoarthritis of the hip: a retrospective comparative study.

PubMed

Park, Ki Deok; Kim, Tai Kon; Bae, Byung Woo; Ahn, JaeKi; Lee, Woo Yong; Park, Yongbum

2015-09-01

Intra-articular steroid injection has been widely used in the management of symptomatic osteoarthritis; however, its frequent use is avoided since there is an increase in the incidence of articular infection and several mechanical side effects such as cartilage breakdown and loss of elasticity of the articular cartilage. For these reasons, nonsteroidal anti-inflammatory drugs instead of corticosteroids can be considered for intra-articular injection. On this basis, we investigated the effects and safety of ultrasound-guided intra-articular ketorolac versus corticosteroid injection for patients with osteoarthritis of the hip. This retrospective study included 98 patients with diagnoses of hip osteoarthritis who underwent ultrasound-guided intra-articular ketorolac or corticosteroid injection. Fifty patients who received ultrasound-guided intra-articular corticosteroid injection were administered a mixture of 0.5% lidocaine and triamcinolone. Forty-eight patients who received ultrasound-guided intra-articular ketorolac injection were administered 0.5% lidocaine and ketorolac. Outcome measurement was assessed using the Harris hip score and verbal numeric pain scale, which were evaluated before the injections and at 1, 3 and 6 months following the injection. Univariate analysis (using the x (2) test) and multiple logistic regression analysis were performed to evaluate the relationship between the possible outcome predictors (injected medications, patients' age, gender, pain duration and Kellgren-Lawrence classification) and the therapeutic effects. The Harris hip score and verbal numeric pain scale were improved at 1, 3 and 6 months after the injection in both groups. No statistical differences in the Harris hip score and verbal numeric pain scale were observed between the groups. The success rate was also not significantly different among the time periods of 1, 3 and 6 months. Multiple logistic regression and univariate analysis showed that injected medications patients' age, gender, pain duration and Kellgren-Lawrence classification were not independent predictors of successful outcome at midterm follow-up. The treatment of osteoarthritis of the hip with intra-articular ketorolac injection is as effective as that with intra-articular corticosteroid injection. Intra-articular ketorolac injection can be considered useful for patients with contraindications to using corticosteroids.

A comparison study of different physical treatments on cartilage matrix derived porous scaffolds for tissue engineering applications

PubMed Central

Moradi, Ali; Pramanik, Sumit; Ataollahi, Forough; Abdul Khalil, Alizan; Kamarul, Tunku; Pingguan-Murphy, Belinda

2014-01-01

Native cartilage matrix derived (CMD) scaffolds from various animal and human sources have drawn attention in cartilage tissue engineering due to the demonstrable presence of bioactive components. Different chemical and physical treatments have been employed to enhance the micro-architecture of CMD scaffolds. In this study we have assessed the typical effects of physical cross-linking methods, namely ultraviolet (UV) light, dehydrothermal (DHT) treatment, and combinations of them on bovine articular CMD porous scaffolds with three different matrix concentrations (5%, 15% and 30%) to assess the relative strengths of each treatment. Our findings suggest that UV and UV–DHT treatments on 15% CMD scaffolds can yield architecturally optimal scaffolds for cartilage tissue engineering. PMID:27877731

Isolated, extra-articular neck and shaft fractures of the 4th and 5th metacarpals: a comparison of transverse and bouquet (intra-medullary) pinning in 67 patients.

PubMed

Sletten, I N; Nordsletten, L; Husby, T; Ødegaard, R A; Hellund, J C; Kvernmo, H D

2012-06-01

Although extra-articular metacarpal fractures are common, there is no consensus on the mode of treatment. We evaluated the outcome in 67 patients operated for isolated, extra-articular fractures in the neck or shaft of the ulnar two metacarpals 28 months post-operatively. There were 22 bouquet (intra-medullary) pinnings and 45 transverse pinnings; 11 were lost to follow-up. Overall, hand function was good, and no difference was detected between the two methods (QuickDASH, grip strength, range of motion, VAS pain and VAS satisfaction). Many patients suffered complications: 12% had a superficial infection (all treated with transverse pinning with wires left exposed); 39% had some impairment in skin sensation; 29% reported cold intolerance; and 10% had other complications. Due to the potential risk of a secondary fracture of the neighbouring metacarpal after transverse pinning, we recommend bouquet (intra-medullary) pinning. We also recommend burying wires beneath the skin surface to avoid infection.

Innovative application of optical techniques to comprehensive study of the etiology of osteoarthritis

NASA Astrophysics Data System (ADS)

Ugryumova, Nadya; Matcher, Stephen J.

2006-08-01

Osteoarthritis is a painful condition, causing restricted mobility in the articular joints. In this paper we present a review of different optical techniques that might be used to clarify the etiology of degeneration of connective joint tissues, such as bone and articular cartilage. Significant correlation (R2 = 0.8) between bone mineral density and scattering coefficient of cortical bone tissue are found by using Integrating Sphere Technique. Optical Coherence Tomography and Polarization-Sensitive Optical Coherence Tomography images of cartilage tissue are presented. They were performed as series of angle-dependant measurements for different location along the surface. Method for spatial mapping the birefringence of equine articular cartilage is proposed. Variations in band spacing of birefringence obtained from visually healthy and abnormal cartilage samples are compared. Visible osteoarthritic lesions are characterized by a loss of the regular birefringence bands shown by normal cartilage. We discuss the hypothesis that some of these variations may be due to changes in intrinsic structure of tissue.

Treatment of focal articular cartilage lesions of the knee with autogenous osteochondral graftsA 2- to 4-year follow-up study.

PubMed

Wang, Ching-Jen

2002-04-01

A retrospective study of 15 patients with 16 knees who underwent osteochondral autografts for focal full thickness articular cartilage defects of the knee with 2- to 4-year follow-up showed 80% good or excellent clinical results. There was no correlation of the clinical results with the underlying diagnoses, including osteonecrosis, osteochondritis dessicans and traumatic cartilage defect, or a size of the lesion smaller than 600 mm(2). However, cartilage lesions larger than 600 mm(2) were associated with increasing fibrous tissue formation and fissuring between the grafts and the host tissues and poor results. The improvement in symptoms appeared time-dependent, ranging from 6 to 16 weeks, suggesting that postoperative protection of the graft is warranted. There was no radiographic progression of degenerative changes of the knee on the medium-term follow-up. Therefore, an autogenous osteochondral graft is considered a good method in the treatment of knees with moderately sized articular cartilage defects.

Three-dimensional T1rho-weighted MRI at 1.5 Tesla.

PubMed

Borthakur, Arijitt; Wheaton, Andrew; Charagundla, Sridhar R; Shapiro, Erik M; Regatte, Ravinder R; Akella, Sarma V S; Kneeland, J Bruce; Reddy, Ravinder

2003-06-01

To design and implement a magnetic resonance imaging (MRI) pulse sequence capable of performing three-dimensional T(1rho)-weighted MRI on a 1.5-T clinical scanner, and determine the optimal sequence parameters, both theoretically and experimentally, so that the energy deposition by the radiofrequency pulses in the sequence, measured as the specific absorption rate (SAR), does not exceed safety guidelines for imaging human subjects. A three-pulse cluster was pre-encoded to a three-dimensional gradient-echo imaging sequence to create a three-dimensional, T(1rho)-weighted MRI pulse sequence. Imaging experiments were performed on a GE clinical scanner with a custom-built knee-coil. We validated the performance of this sequence by imaging articular cartilage of a bovine patella and comparing T(1rho) values measured by this sequence to those obtained with a previously tested two-dimensional imaging sequence. Using a previously developed model for SAR calculation, the imaging parameters were adjusted such that the energy deposition by the radiofrequency pulses in the sequence did not exceed safety guidelines for imaging human subjects. The actual temperature increase due to the sequence was measured in a phantom by a MRI-based temperature mapping technique. Following these experiments, the performance of this sequence was demonstrated in vivo by obtaining T(1rho)-weighted images of the knee joint of a healthy individual. Calculated T(1rho) of articular cartilage in the specimen was similar for both and three-dimensional and two-dimensional methods (84 +/- 2 msec and 80 +/- 3 msec, respectively). The temperature increase in the phantom resulting from the sequence was 0.015 degrees C, which is well below the established safety guidelines. Images of the human knee joint in vivo demonstrate a clear delineation of cartilage from surrounding tissues. We developed and implemented a three-dimensional T(1rho)-weighted pulse sequence on a 1.5-T clinical scanner. Copyright 2003 Wiley-Liss, Inc.

Assessment of strategies to increase chondrocyte viability in cryopreserved human osteochondral allografts: evaluation of the glycosylated hydroquinone, arbutin.

PubMed

Rosa, S C; Gonçalves, J; Judas, F; Lopes, C; Mendes, A F

2009-12-01

Allogeneic cartilage is used to repair damaged areas of articular cartilage, requiring the presence of living chondrocytes. So far, no preservation method can effectively meet that purpose. Identification of more effective cryoprotective agents (CPAs) can contribute to this goal. The aim of this study was to determine whether the glycosylated hydroquinone, arbutin, alone or in combination with low concentrations of other CPAs, has cryoprotective properties towards human articular cartilage. Human tibial plateaus were procured from multi-organ donors, with the approval of the Ethics Committee of the University Hospital of Coimbra. The tibial plateaus were treated with or without arbutin (50 or 100mM), alone or in combination with various concentrations of dimethyl sulfoxide (DMSO) and glycerol, for 0.5-1.5h/37 degrees C, then frozen at -20 degrees C and 24h later transferred to a biofreezer at -80 degrees C. Two to 3 months later, thawing was achieved by immersion in cell culture medium at 37 degrees C/1h. Chondrocyte viability was assessed before and after freeze-thawing using a colorimetric assay based on the cell's metabolic activity and fluorescent dyes to evaluate cell membrane integrity. Before freezing, chondrocyte metabolic activity was identical in all the conditions tested. After freeze-thawing, the highest activity, corresponding to 34.2+/-2.1% of that in the Fresh Control, was achieved in tibial plateaus incubated in 50mM arbutin for 1h whereas in those left untreated it was 11.1+/-4.7. Addition of DMSO and glycerol to arbutin did not increase chondrocyte viability any further. Fluorescence microscopy confirmed these results and showed that living chondrocytes were mainly restricted to the superficial cartilage layers. Arbutin seems to be an effective cryoprotective agent for osteochondral allografts with potential benefits over DMSO and glycerol.

Combined Volar and Dorsal Approach for Fixation of Comminuted Intra-Articular Distal Radial Fractures.

PubMed

Medlock, G; Smith, M; Johnstone, A J

2018-07-01

Purpose  Multifragmentary intra-articular fractures displaced in multiple planes are a challenge. We use a reproducible technique of fracture and articular reduction using an initial volar approach targeting reduction in the volar lunate facet first with plate and unicortical locking screws. This creates a template for reduction in dorsal fragments through a dorsal approach. Our study investigated the radiological, clinical, and functional outcomes of patients treated with this technique. Materials and Methods  We reviewed the postoperative radiographs and notes of 18 patients that had this method of fixation between the years 2008 and 2015, the mean age being 43. These patients were reviewed functionally on average 2 years and 3 months following their definitive operation. Results  Normal alignment and length to the distal radius were restored with on average a 0.6 mm articular step. The average range of motion was 64% and preservation of grip strength was 71% compared with the uninjured wrist. Functional assessment averages were 29 for both the quick Disabilities of the Arm, Shoulder and Hand (DASH) and for Patient Rated Wrist Evaluation. The modified system of Green and O'Brien had results of good in 10, fair in 7, and poor in 1. With respect to the Gartland and Werley system, three patients had an excellent result, four had a good result, six had a fair result, and five had a poor result. The mean arthritic grading was 1 (grading 0-3) according to Knirk and Jupiter. Conclusion  This reproducible technique provides an option for these devastating fractures providing a functioning wrist with all of the patients returning to their original form of employment.

Clinical potential and challenges of using genetically modified cells for articular cartilage repair.

PubMed

Madry, Henning; Cucchiarini, Magali

2011-06-01

Articular cartilage defects do not regenerate. Transplantation of autologous articular chondrocytes, which is clinically being performed since several decades, laid the foundation for the transplantation of genetically modified cells, which may serve the dual role of providing a cell population capable of chondrogenesis and an additional stimulus for targeted articular cartilage repair. Experimental data generated so far have shown that genetically modified articular chondrocytes and mesenchymal stem cells (MSC) allow for sustained transgene expression when transplanted into articular cartilage defects in vivo. Overexpression of therapeutic factors enhances the structural features of the cartilaginous repair tissue. Combined overexpression of genes with complementary mechanisms of action is also feasible, holding promises for further enhancement of articular cartilage repair. Significant benefits have been also observed in preclinical animal models that are, in principle, more appropriate to the clinical situation. Finally, there is convincing proof of concept based on a phase I clinical gene therapy study in which transduced fibroblasts were injected into the metacarpophalangeal joints of patients without adverse events. To realize the full clinical potential of this approach, issues that need to be addressed include its safety, the choice of the ideal gene vector system allowing for a long-term transgene expression, the identification of the optimal therapeutic gene(s), the transplantation without or with supportive biomaterials, and the establishment of the optimal dose of modified cells. As safe techniques for generating genetically engineered articular chondrocytes and MSCs are available, they may eventually represent new avenues for improved cell-based therapies for articular cartilage repair. This, in turn, may provide an important step toward the unanswered question of articular cartilage regeneration.

Cartilage Regeneration in Osteoarthritic Patients by a Composite of Allogeneic Umbilical Cord Blood-Derived Mesenchymal Stem Cells and Hyaluronate Hydrogel: Results from a Clinical Trial for Safety and Proof-of-Concept with 7 Years of Extended Follow-Up.

PubMed

Park, Yong-Beom; Ha, Chul-Won; Lee, Choong-Hee; Yoon, Young Cheol; Park, Yong-Geun

2017-02-01

Few methods are available to regenerate articular cartilage defects in patients with osteoarthritis. We aimed to assess the safety and efficacy of articular cartilage regeneration by a novel medicinal product composed of allogeneic human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs). Patients with Kellgren-Lawrence grade 3 osteoarthritis and International Cartilage Repair Society (ICRS) grade 4 cartilage defects were enrolled in this clinical trial. The stem cell-based medicinal product (a composite of culture-expanded allogeneic hUCB-MSCs and hyaluronic acid hydrogel [Cartistem]) was applied to the lesion site. Safety was assessed by the World Health Organization common toxicity criteria. The primary efficacy outcome was ICRS cartilage repair assessed by arthroscopy at 12 weeks. The secondary efficacy outcome was visual analog scale (VAS) score for pain on walking. During a 7-year extended follow-up, we evaluated safety, VAS score, International Knee Documentation Committee (IKDC) subjective score, magnetic resonance imaging (MRI) findings, and histological evaluations. Seven participants were enrolled. Maturing repair tissue was observed at the 12-week arthroscopic evaluation. The VAS and IKDC scores were improved at 24 weeks. The improved clinical outcomes were stable over 7 years of follow-up. The histological findings at 1 year showed hyaline-like cartilage. MRI at 3 years showed persistence of the regenerated cartilage. Only five mild to moderate treatment-emergent adverse events were observed. There were no cases of osteogenesis or tumorigenesis over 7 years. The application of this novel stem cell-based medicinal product appears to be safe and effective for the regeneration of durable articular cartilage in osteoarthritic knees. Stem Cells Translational Medicine 2017;6:613-621. © 2016 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Quantitative Gross and CT measurements of Cadaveric Cervical Vertebrae (C3 – C6) as Guidelines for the Lateral mass screw fixation

PubMed Central

Heinneman, Thomas E.; Conti, Mathew S.; Dossous, Paul-Michel F.; Dillon, David J.; Tsiouris, Apostolos J.; Pyo, Se Young; Mtui, Estomih P.; Härtl, Roger

2016-01-01

Background Lateral mass screw fixation is the treatment of choice for posterior cervical stabilization. Long or misdirected screws carry a risk of injury to spinal nerve roots or vertebral artery. This study was aimed to assess the gross anatomic and CT measurements of typical cervical vertebrae for the selection of lateral mass screws. Methods Dimensions of the articular pillars were measured on 1) Dry cervical vertebrae with Vernier calipers and 2) Multiplanar reformations of CT scans of the same vertebrae with Viewer software package. The data was statistically evaluated. Results The transverse diameter of the articular pillars with Vernier calipers varied from 6.0 to 15.4 mm (mean=10.5 mm ± 1.5) and on CT scans ranged from 8.2 – 16.1 mm (mean=11.6 mm ± 1.4). The antero-posterior diameter, an estimate of the screw length by Roy-Camille technique varied from 3.9 to 12.7 mm (mean=8.6 mm ± 1.6) by Vernier calipers and from 6.4 to 13.3 mm (mean=9.1 ± 1.2) on CT scans. The oblique AP diameter, an estimate of screw length by Magerl method varied from 10.8 to 20.3 mm (mean=14.9 mm ± 1.8) by Vernier calipers and from 11.4 to 19.3 mm (mean=14.5 mm ± 1.7) on CT. The CT measurements for height, transverse and AP diameter of the articular pillars were 0.5 - 1.0 mm larger than dimensions by Vernier calipers. No statistically significant difference was observed between the caliper and CT measurements for the oblique AP diameter. Conclusion CT measurements of the articular pillars may slightly overestimate the desired screw length selected by spine surgeons when compared to actual anatomy. Although means of the articular pillars correspond to the screw lengths used, substantial number of observations below 10 mm for Roy-Camille trajectory and below 14 mm for Magerl trajectory requires careful preoperative planning and intra-operative confirmation to avoid long/misdirected lateral mass screws. PMID:28377857

Quantitative three-dimensional shape analysis of the proximal hallucial metatarsal articular surface in Homo, Pan, Gorilla, and Hylobates.

PubMed

Proctor, Daniel J; Broadfield, Douglas; Proctor, Kristopher

2008-02-01

Multidimensional morphometrics is used to compare the proximal articular surface of the first metatarsal between Homo, Pan, Gorilla, Hylobates, and the hominin fossils A.L. 333-54 (A. afarensis), SKX 5017 (P. robustus), and OH 8 (H. habilis). Statistically significant differences in articular surface morphology exist between H. sapiens and the apes, and between ape groups. Ape groups are characterized by greater surface depth, an obliquely curved articular surface through the dorso-lateral and medio-plantar regions, and a wider medio-lateral surface relative to the dorso-plantar height. The OH 8 articular surface is indistinguishable from H. sapiens, while A.L. 333-54 and SKX 5017 more closely resemble the apes. P. robustus and A. afarensis exhibit ape-like oblique curvature of the articular surface. Copyright 2007 Wiley-Liss, Inc.

Widespread epigenomic, transcriptomic and proteomic differences between hip osteophytic and articular chondrocytes in osteoarthritis.

PubMed

Steinberg, Julia; Brooks, Roger A; Southam, Lorraine; Bhatnagar, Sahir; Roumeliotis, Theodoros I; Hatzikotoulas, Konstantinos; Zengini, Eleni; Wilkinson, J Mark; Choudhary, Jyoti S; McCaskie, Andrew W; Zeggini, Eleftheria

2018-05-08

To identify molecular differences between chondrocytes from osteophytic and articular cartilage tissue from OA patients. We investigated genes and pathways by combining genome-wide DNA methylation, RNA sequencing and quantitative proteomics in isolated primary chondrocytes from the cartilaginous layer of osteophytes and matched areas of low- and high-grade articular cartilage across nine patients with OA undergoing hip replacement surgery. Chondrocytes from osteophytic cartilage showed widespread differences to low-grade articular cartilage chondrocytes. These differences were similar to, but more pronounced than, differences between chondrocytes from osteophytic and high-grade articular cartilage, and more pronounced than differences between high- and low-grade articular cartilage. We identified 56 genes with significant differences between osteophytic chondrocytes and low-grade articular cartilage chondrocytes on all three omics levels. Several of these genes have known roles in OA, including ALDH1A2 and cartilage oligomeric matrix protein, which have functional genetic variants associated with OA from genome-wide association studies. An integrative gene ontology enrichment analysis showed that differences between osteophytic and low-grade articular cartilage chondrocytes are associated with extracellular matrix organization, skeletal system development, platelet aggregation and regulation of ERK1 and ERK2 cascade. We present a first comprehensive view of the molecular landscape of chondrocytes from osteophytic cartilage as compared with articular cartilage chondrocytes from the same joints in OA. We found robust changes at genes relevant to chondrocyte function, providing insight into biological processes involved in osteophyte development and thus OA progression.

A Comparison of Outcomes of Particulated Juvenile Articular Cartilage and Bone Marrow Aspirate Concentrate for Articular Cartilage Lesions of the Talus.

PubMed

Lanham, Nathan S; Carroll, John J; Cooper, Minton T; Perumal, Venkat; Park, Joseph S

2017-08-01

Articular cartilage lesions of the talus remain a challenging clinical problem because of the lack of natural regeneration and limited treatment options. Microfracture is often the first-line therapy, however lesions larger than 1.5 cm 2 have been shown to not do as well with this treatment method. The objective of this retrospective study was to evaluate the outcomes of iliac crest bone marrow aspirate concentrate/collagen scaffold (ICBMA) and particulated juvenile articular cartilage (PJAC) for larger articular cartilage lesions of the talus. Fifteen patients undergoing ICBMA or PJAC for articular cartilage lesions of the talus from 2010 to 2013 were reviewed. Twelve patients, 6 from each treatment option, were included in the study. American Orthopaedic Foot and Ankle Surgeons (AOFAS), Foot and Ankle Ability Measure (FAAM), and Short Form-12 (SF-12) outcome scores were collected for each patient. The mean age was 34.7 ± 14.8 years for ICBMA and 31.5 ± 7.4 years for PJAC. Lesion size was 2.0 ± 1.1 cm 2 for ICBMA and 1.9 ± 0.9 cm 2 for PJAC. At a mean follow-up of 25.7 months (range, 12-42 months), the mean AOFAS score was 71.33 for ICBMA and 95.83 for PJAC (  P = .019). The FAAM activities of daily living subscale mean was 77.77 for ICBMA and 97.02 for PJAC (   P = .027). The mean FAAM sports subscale was 45.14 for ICBMA and 86.31 for PJAC (  P = .054). The SF-12 physical health mean was 47.58 for ICBMA and 53.98 for PJAC (  P = .315). The SF-12 mental health mean was 53.25 for ICBMA and 57.8 for PJAC (  P = .315). One patient in treated initially with ICBMA underwent revision fixation for nonunion of their medial malleolar osteotomy, which ultimately resulted in removal of hardware and tibiotalar arthrodesis at 2 years from the index procedure. In the present analysis, PJAC yields better clinical outcomes at 2 years when compared with ICBMA for articular cartilage lesions of the talus that were on average greater than 1.5cm 2 . Therapeutic, Level IV: Retrospective, Case series.

Advantages of the Ilizarov external fixation in the management of intra-articular fractures of the distal tibia

PubMed Central

Vasiliadis, Elias S; Grivas, Theodoros B; Psarakis, Spyridon A; Papavasileiou, Evangelos; Kaspiris, Angelos; Triantafyllopoulos, Georgios

2009-01-01

Background Treatment of distal tibial intra-articular fractures is challenging due to the difficulties in achieving anatomical reduction of the articular surface and the instability which may occur due to ligamentous and soft tissue injury. The purpose of this study is to present an algorithm in the application of external fixation in the management of intra-articular fractures of the distal tibia either from axial compression or from torsional forces. Materials and methods Thirty two patients with intra-articular fractures of the distal tibia have been studied. Based on the mechanism of injury they were divided into two groups. Group I includes 17 fractures due to axial compression and group II 15 fractures due to torsional force. An Ilizarov external fixation was used in 15 patients (11 of group I and 4 of group II). In 17 cases (6 of group I and 11 of group II) a unilateral hinged external fixator was used. In 7 out of 17 fractures of group I an additional fixation of the fibula was performed. Results All fractures were healed. The mean time of removal of the external fixator was 11 weeks for group I and 10 weeks for group II. In group I, 5 patients had radiological osteoarthritic lesions (grade III and IV) but only 2 were symptomatic. Delayed union occurred in 3 patients of group I with fixed fibula. Other complications included one patient of group II with subluxation of the ankle joint after removal of the hinged external fixator, in 2 patients reduction found to be insufficient during the postoperative follow up and were revised and 6 patients had a residual pain. The range of ankle joint motion was larger in group II. Conclusion Intra-articular fractures of the distal tibia due to axial compression are usually complicated with cartilaginous problems and are requiring anatomical reduction of the articular surface. Fractures due to torsional forces are complicated with ankle instability and reduction should be augmented with ligament repair, in order to restore normal movement of talus against the mortise. Both Ilizarov and hinged external fixators are unable to restore ligamentous stability. External fixation is recommended only for fractures of the ankle joint caused by axial compression because it is biomechanically superior and has a lower complication rate. PMID:19754962

Pathomechanics of Post-Traumatic OA Development in the Military Following Articular Fracture

DTIC Science & Technology

2017-10-01

AWARD NUMBER: W81XWH-15-2-0087 TITLE: Pathomechanics of Post -Traumatic OA Development in the Military Following Articular Fracture PRINCIPAL...Sep 2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Pathomechanics of Post -Traumatic OA Development in the Military Following Articular Fracture 5b...develop new models for predicting the risk of post -traumatic osteoarthritis (PTOA) following intra-articular fracture (IAF). We have analyzed pre

Zone-specific cell biosynthetic activity in mature bovine articular cartilage: a new method using confocal microscopic stereology and quantitative autoradiography.

PubMed

Wong, M; Wuethrich, P; Eggli, P; Hunziker, E

1996-05-01

A new methodology was developed to measure spatial variations in chondrocyte/matrix structural parameters and chondrocyte biosynthetic activity in articular cartilage. This technique is based on the use of a laser scanning confocal microscope that can "optically" section chemically fixed, unembedded tissue. The confocal images are used for morphometric measurement of stereologic parameters such as cell density (cells/mm3), cell volume fraction (%), surface density (l/cm), mean cell volume (micron3), and mean cell surface area (micron2). Adjacent pieces of tissue are simultaneously processed for conventional liquid emulsion autoradiography, and a semiautomated grain counting program is used to measure the silver grain density at regions corresponding to the same sites used for structural measurements. An estimate of chondrocyte biosynthetic activity in terms of grains per cell is obtained by dividing the value for grain density by that for cell density. In this paper, the newly developed methodology was applied to characterize the zone-specific behavior of adult articular cartilage in the free-swelling state. Cylinders of young adult bovine articular cartilage were labelled with either [3H]proline or [35S]sulfate, and chondrocyte biosynthesis and structural parameters were measured from the articular surface to the tidemark. The results showed that chondrocytes of the radial zone occupied twice the volume and surface area of the chondrocytes of the superficial zone but were 10 times more synthetically active. This efficient and unbiased technique may prove useful in studying the correlation between mechanically induced changes in cell form and biosynthetic activity within inhomogeneous tissue as well as metabolic changes in cartilage due to ageing and disease.

Finite element analysis of intramedullary nailing and double locking plate for treating extra-articular proximal tibial fractures.

PubMed

Chen, Fancheng; Huang, Xiaowei; Ya, Yingsun; Ma, Fenfen; Qian, Zhi; Shi, Jifei; Guo, Shuolei; Yu, Baoqing

2018-01-16

Proximal tibia fractures are one of the most familiar fractures. Surgical approaches are usually needed for anatomical reduction. However, no single treatment method has been widely established as the standard care. Our present study aims to compare the stress and stability of intramedullary nails (IMN) fixation and double locking plate (DLP) fixation in the treatment of extra-articular proximal tibial fractures. A three-dimensional (3D) finite element model of the extra-articular proximal tibial fracture, whose 2-cm bone gap began 7 cm from the tibial plateau articular surface, was created fixed by different fixation implants. The axial compressive load on an adult knee during single-limb stance was imitated by an axial force of 2500 N with a distribution of 60% to the medial compartment, while the distal end was fixed effectively. The equivalent von Mises stress and displacement of the model was used as the output measures for analysis. The maximal equivalent von Mises stress value of the system in the IMN model was 293.23 MPa, which was higher comparing against that in the DLP fixation model (147.04 MPa). And the mean stress of the model in the IMN model (9.25 MPa) was higher than that of the DLP fixation system in terms of equivalent von Mises stress (EVMS) (P < 0.0001). The maximal value of displacement (sum) in the IMN system was 8.82 mm, which was lower than that in the DLP fixation system (9.48 mm). This study demonstrated that the stability provided by the locking plate fixation system was superior to the intramedullary nails fixation system and served as an alternative fixation for the extra-articular proximal tibial fractures of young patients.

Fractures of the Tibial Plateau Involve Similar Energies as the Tibial Pilon but Greater Articular Surface Involvement

PubMed Central

Dibbern, Kevin; Kempton, Laurence B.; Higgins, Thomas F.; Morshed, Saam; McKinley, Todd O.; Marsh, J. Lawrence; Anderson, Donald D.

2016-01-01

Patients with tibial pilon fractures have a higher incidence of post-traumatic osteoarthritis than those with fractures of the tibial plateau. This may indicate that pilon fractures present a greater mechanical insult to the joint than do plateau fractures. We tested the hypothesis that fracture energy and articular fracture edge length, two independent indicators of severity, are higher in pilon than plateau fractures. We also evaluated if clinical fracture classification systems accurately reflect severity. Seventy-five tibial plateau fractures and fifty-two tibial pilon fractures from a multi-institutional study were selected to span the spectrum of severity. Fracture severity measures were calculated using objective CT-based image analysis methods. The ranges of fracture energies measured for tibial plateau and pilon fractures were 3.2 to 33.2 Joules (J) and 3.6 to 32.2 J, respectively, and articular fracture edge lengths were 68.0 to 493.0 mm and 56.1 to 288.6 mm, respectively. There were no differences in the fracture energies between the two fracture types, but plateau fractures had greater articular fracture edge lengths (p<0.001). The clinical fracture classifications generally reflected severity, but there was substantial overlap of fracture severity measures between different classes. Clinical Significance Similar fracture energies with different degrees of articular surface involvement suggest a possible explanation for dissimilar rates of post-traumatic osteoarthritis for fractures of the tibial plateau compared to the tibial pilon. The substantial overlap of severity measures between different fracture classes may well have confounded prior clinical studies relying on fracture classification as a surrogate for severity. PMID:27381653

Evaluation of intra-articular injection of autologous platelet lysate (PL) in horses with osteoarthritis of the distal interphalangeal joint.

PubMed

Tyrnenopoulou, Panagiota; Diakakis, Nikolaos; Karayannopoulou, Maria; Savvas, Ioannis; Koliakos, Georgios

2016-06-01

Regenerative medicine has become one of the most promising therapies of equine osteoarthritis. Platelet lysate (PL) is rich in bioactive proteins and growth factors that play a crucial role in tissue healing. To evaluate the efficacy of intra-articularly injected autologous PL in equine athletes with naturally occurring osteoarthritis. Fifteen warmblood geldings aged 8-19 years with osteoarthritis of the distal interphalangeal joint were included in this study. They were randomly divided into two groups; 10 horses received intra-articular injections of PL and 5 of normal saline (controls). Before treatment, platelet-derived growth factor (PDGF) levels in basal plasma and prepared PL were estimated. Each joint was injected twice within a three-week period. Lameness was evaluated using the American Association of Equine Practitioners grading system, before treatment and 10 days after each intra-articular injection. Horses were examined fortnightly for one year. Radiographic examination was performed six months post-treatment. The generalized estimating equation test was used for statistical analysis. Acceptable levels of PDGF were detected in PLs (mean ± SD: 258.0 ± 52.3 pg/ml). The majority of horses (9/10) responded positively to PL treatment presenting lower lameness grades (p < 0.0005) compared to controls 10 days after the second injection, and returned to normal athletic activity. Radiographs revealed no changes in osteoarthritis lesions six months after treatment. One year post-injections, however, all horses relapsed to their initial degree of lameness. Intra-articularly injected autologous PL is an efficient method for temporarily managing osteoarthritis of the distal interphalangeal joint in athletic horses.

Assessing adverse effects of intra-articular botulinum toxin A in healthy Beagle dogs: A placebo-controlled, blinded, randomized trial

PubMed Central

Jokinen, Tarja S.; Syrjä, Pernilla; Junnila, Jouni; Hielm-Björkman, Anna; Laitinen-Vapaavuori, Outi

2018-01-01

Objective To investigate the clinical, cytological, and histopathological adverse effects of intra-articularly injected botulinum toxin A in dogs and to study whether the toxin spreads from the joint after the injection. Methods A longitudinal, placebo-controlled, randomized clinical trial was conducted with six healthy laboratory Beagle dogs. Stifle joints were randomized to receive either 30 IU of onabotulinum toxin A or placebo in a 1:1 ratio. Adverse effects and spread of the toxin were examined by evaluating dynamic and static weight-bearing of the injected limbs, by assessing painless range of motion and pain on palpation of joints, and by performing synovial fluid analysis, neurological examination, and electrophysiological recordings at different examination time-points in a 12-week period after the injections. The dogs were then euthanized and autopsy and histopathological examination of joint structures and adjacent muscles and nerves were performed. Results Intra-articular botulinum toxin A did not cause local weakness or injection site pain. Instead, static weight-bearing and painless range of motion of stifle joints decreased in the placebo limbs. No clinically significant abnormalities associated with intra-articular botulinum toxin A were detected in the neurological examinations. Electrophysiological recordings showed low compound muscle action potentials in two dogs in the botulinum toxin A-injected limb. No significant changes were detected in the synovial fluid. Autopsy and histopathological examination of the joint and adjacent muscles and nerves did not reveal histopathological adverse effects of the toxin. Conclusion Intra-articular botulinum toxin A does not produce significant clinical, cytological, or histopathological adverse effects in healthy dogs. Based on the electrophysiological recordings, the toxin may spread from the joint, but its clinical impact seems to be low. PMID:29320549

Inducing articular cartilage phenotype in costochondral cells

PubMed Central

2013-01-01

Introduction Costochondral cells may be isolated with minimal donor site morbidity and are unaffected by pathologies of the diarthrodial joints. Identification of optimal exogenous stimuli will allow abundant and robust hyaline articular cartilage to be formed from this cell source. Methods In a three factor, two level full factorial design, the effects of hydrostatic pressure (HP), transforming growth factor β1 (TGF-β1), and chondroitinase ABC (C-ABC), and all resulting combinations, were assessed in third passage expanded, redifferentiated costochondral cells. After 4 wks, the new cartilage was assessed for matrix content, superficial zone protein (SZP), and mechanical properties. Results Hyaline articular cartilage was generated, demonstrating the presence of type II collagen and SZP, and the absence of type I collagen. TGF-β1 upregulated collagen synthesis by 175% and glycosaminoglycan synthesis by 75%, resulting in a nearly 200% increase in tensile and compressive moduli. C-ABC significantly increased collagen content, and fibril density and diameter, leading to a 125% increase in tensile modulus. Hydrostatic pressure increased fibril diameter by 30% and tensile modulus by 45%. Combining TGF-β1 with C-ABC synergistically increased collagen content by 300% and tensile strength by 320%, over control. No significant differences were observed between C-ABC/TGF-β1 dual treatment and HP/C-ABC/TGF-β1. Conclusions Employing biochemical, biophysical, and mechanical stimuli generated robust hyaline articular cartilage with a tensile modulus of 2 MPa and a compressive instantaneous modulus of 650 kPa. Using expanded, redifferentiated costochondral cells in the self-assembling process allows for recapitulation of robust mechanical properties, and induced SZP expression, key characteristics of functional articular cartilage. PMID:24330640

A simulation trainer for complex articular fracture surgery.

PubMed

Yehyawi, Tameem M; Thomas, Thaddeus P; Ohrt, Gary T; Marsh, J Lawrence; Karam, Matthew D; Brown, Thomas D; Anderson, Donald D

2013-07-03

The purposes of this study were (1) to develop a physical model to improve articular fracture reduction skills, (2) to develop objective assessment methods to evaluate these skills, and (3) to assess the construct validity of the simulation. A surgical simulation was staged utilizing surrogate tibial plafond fractures. Multiple three-segment radio-opacified polyurethane foam fracture models were produced from the same mold, ensuring uniform surgical complexity between trials. Using fluoroscopic guidance, five senior and seven junior orthopaedic residents reduced the fracture through a limited anterior window. The residents were assessed on the basis of time to completion, hand movements (tracked with use of a motion capture system), and quality of the obtained reduction. All but three of the residents successfully reduced and fixed the fracture fragments (one senior resident and two junior residents completed the reduction but were unsuccessful in fixating all fragments). Senior residents had an average time to completion of 13.43 minutes, an average gross articular step-off of 3.00 mm, discrete hand motions of 540 actions, and a cumulative hand motion distance of 79 m. Junior residents had an average time to completion of 14.75 minutes, an average gross articular step-off of 3.09 mm, discrete hand motions of 511 actions, and a cumulative hand motion distance of 390 m. The large difference in cumulative hand motion distance, despite comparable numbers of discrete hand motion events, indicates that senior residents were more precise in their hand motions. The present experiment establishes the basic construct validity of the simulation trainer. Further studies are required to demonstrate that this laboratory-based model for articular fracture reduction training, along with an objective assessment of performance, can be used to improve resident surgical skills.

Techniques and Applications of in vivo Diffusion Imaging of Articular Cartilage

PubMed Central

Raya, José G.

2014-01-01

Early in the process of osteoarthritis (OA) the composition (water, proteoglycan [PG], and collagen) and structure of articular cartilage is altered leading to changes in its mechanical properties. A technique that can assess the composition and structure of the cartilage in vivo can provide insight in the mechanical integrity of articular cartilage and become a powerful tool for the early diagnosis of OA. Diffusion tensor imaging (DTI) has been proposed as a biomarker for cartilage composition and structure. DTI is sensitive to the PG content through the mean diffusivity (MD) and to the collagen architecture through the fractional anisotropy (FA). However, the acquisition of DTI of articular cartilage in vivo is challenging due to the short T2 of articular cartilage (~40 ms at 3 T) and the high resolution needed (0.5–0.7 mm in plane) to depict the cartilage anatomy. We describe the pulse sequences used for in vivo DTI of articular cartilage and discus general strategies for protocol optimization. We provide a comprehensive review of measurements of DTI of articular cartilage from ex vivo validation experiments to its recent clinical applications. PMID:25865215

Evaluation of Contrast Extravasation as a Diagnostic Criterion in the Evaluation of Arthroscopically Proven HAGL/pHAGL Lesions

PubMed Central

Maldjian, Catherine; Khanna, Vineet; Bradley, James; Adam, Richard

2014-01-01

Purpose. The validity of preoperative MRI in diagnosing HAGL lesions is debated. Various investigations have produced mixed results with regard to the utility of MRI. The purpose of this investigation is to apply a novel method of diagnosing HAGL/pHAGL lesions by looking at contrast extravasation and to evaluate the reliability of such extravasation of contrast into an extra-articular space as a sign of HAGL/pHAGL lesion. Methods. We utilized specific criteria to define contrast extravasation. We evaluated these criteria in 12 patients with arthroscopically proven HAGL/pHAGL lesion. We also evaluated these criteria in a control group. Results. Contrast extravasation occurred in over 83% of arthroscopically positive cases. Contrast extravasation as a diagnostic criterion in the evaluation of HAGL/pHAGL lesions demonstrated a high interobserver degree of agreement. Conclusions. In conclusion, extra-articular contrast extravasation may serve as a valid and reliable sign of HAGL and pHAGL lesions, provided stringent criteria are maintained to assure that the contrast lies in an extra-articular location. In cases where extravasation is not present, the “J” sign, though nonspecific, may be the only evidence of subtle HAGL and pHAGL lesions. Level of Evidence. Level IV, Retrospective Case-Control series. PMID:25530880

Effect of rhBMP-2 on tibial plateau fractures in a canine model.

PubMed

Schaefer, Susan L; Lu, Yan; Seeherman, Howard; Li, X Jian; Lopez, Mandi J; Markel, Mark D

2009-04-01

This study was to determine the efficacy of recombinant human bone morphogenetic protien-2 (rhBMP-2)/calcium phosphate matrix (CPX) paste to accelerate healing in a canine articular fracture model with associated subchondral defect. rhBMP-2/CPX (BMP), CPX alone (CPX) or autogenous bone graft (ABG) was administered to a canine articular tibial plateau osteotomy with a subchondral defect in each of 21 female dogs. The unoperated contralateral limbs served as controls. Ground reaction forces, synovial fluid, radiographic changes, mechanical testing, bone density, and histology of bone and synovium were analyzed at 6 weeks after surgery. Radiographic analysis demonstrated that the BMP and CPX groups showed improved bony healing compared to the ABG group at week 6. Histomorphometric analysis demonstrated that the BMP group had significantly increased trabecular bone volume compared to the CPX and ABG groups. Mechanical testing revealed that the BMP group had significantly greater maximum failure loads than the ABG group. Histological analysis demonstrated that the BMP group had significantly less sub-synovial inflammation than CPX group. This study demonstrated that rhBMP-2/CPX accelerated healing of articular fractures with subchondral defect compared to ABG in most of the parameters evaluated, and had less subsynovial inflammation than the CPX alone in a canine model.

Ultra-high field diffusion tensor imaging of articular cartilage correlated with histology and scanning electron microscopy.

PubMed

Raya, José G; Arnoldi, Andreas P; Weber, Daniel L; Filidoro, Lucianna; Dietrich, Olaf; Adam-Neumair, Silvia; Mützel, Elisabeth; Melkus, Gerd; Putz, Reinhard; Reiser, Maximilian F; Jakob, Peter M; Glaser, Christian

2011-08-01

To investigate the relationship of the different diffusion tensor imaging (DTI) parameters (ADC, FA, and first eigenvector (EV)) to the constituents (proteoglycans and collagen), the zonal arrangement of the collagen network, and mechanical loading of articular cartilage. DTI of eight cartilage-on-bone samples of healthy human patellar cartilage was performed at 17.6 T. Three samples were additionally imaged under indentation loading. After DTI, samples underwent biomechanical testing, safranin-O staining for semiquantitative proteoglycan estimation, and scanning electron microscopy (SEM) for depicting collagen architecture. From the articular surface to the bone-cartilage interface, ADC continuously decreased and FA increased. Cartilage zonal heights calculated from EVs strongly correlated with SEM-derived zonal heights (P < 0.01, r (2)=0.87). Compression reduced ADC in the superficial 30% of cartilage and increased FA in the superficial 5% of cartilage. Reorientation of the EVs indicative of collagen fiber reorientation under the indenter was observed. No significant correlation was found between ADC, FA, and compressive stiffness. Correlating ADC and FA with proteoglycan and collagen content suggests that diffusion is dominated by different depth-dependent mechanisms within cartilage. Knowledge of the spatial distribution of the DTI parameters and their variation contributes to form a database for future analysis of defective cartilage.

Articular Eminence Inclination in Medieval and Contemporary Croatian Population

PubMed

Kranjčić, Josip; Šlaus, Mario; Vodanović, Marin; Peršić, Sanja; Vojvodić, Denis

2016-12-01

Articular eminence inclination (AEI) of the temporomandibular joint leads the mandible in its movements. Therefore, the aim of the present study was to determine AEI values in medieval (MP) and recent (RP) Croatian population. The study was carried out on two groups of specimens: first group with 30 MP human dry skulls, while the other, serving as control group consisted of 137 dry skulls. The AEI was measured on lateral digital skull images as the angle between the best fi t line drawn along the posterior wall of the articular eminence and the Frankfurt horizontal plane. No statistically significant (p>0.05) differences between the left and right side AEI were found between MP skulls and RP skulls. The mean value of MP AEI was 45.5˚, with a range of 20.9˚-64˚. The mean RP AEI value was steeper (61.99˚), with a range of 30˚-94˚. Difference between the mean MP and RP AEI values was statistically significant (p<0.05). Values of AEI vary a lot. Nonsignificant differences between the left and right side AEI confirmed the natural left-right side asymmetry. The values of AEI differ between the RP and MP groups, most probably due to different type of food consumption in medieval time, and consequently different masticatory loads and forces.

Blood cells transcriptomics as source of potential biomarkers of articular health improvement: effects of oral intake of a rooster combs extract rich in hyaluronic acid.

PubMed

Sánchez, Juana; Bonet, M Luisa; Keijer, Jaap; van Schothorst, Evert M; Mölller, Ingrid; Chetrit, Carles; Martinez-Puig, Daniel; Palou, Andreu

2014-09-01

The aim of the study was to explore peripheral blood gene expression as a source of biomarkers of joint health improvement related to glycosaminoglycan (GAG) intake in humans. Healthy individuals with joint discomfort were enrolled in a randomized, double-blind, placebo-controlled intervention study in humans. Subjects ate control yoghurt or yoghurt supplemented with a recently authorized novel food in Europe containing hyaluronic acid (65 %) from rooster comb (Mobilee™ as commercial name) for 90 days. Effects on functional quality-of-life parameters related to joint health were assessed. Whole-genome microarray analysis of peripheral blood samples from a subset of 20 subjects (10 placebo and 10 supplemented) collected pre- and post-intervention was performed. Mobilee™ supplementation reduced articular pain intensity and synovial effusion and improved knee muscular strength indicators as compared to placebo. About 157 coding genes were differentially expressed in blood cells between supplemented and placebo groups post-intervention, but not pre-intervention (p < 0.05; fold change ≥1.2). Among them, a reduced gene expression of glucuronidase-beta (GUSB), matrix metallopeptidase 23B (MMP23B), xylosyltransferase II (XYLT2), and heparan sulfate 6-O-sulfotransferase 1 (HS6ST1) was found in the supplemented group. Correlation analysis indicated a direct relationship between blood cell gene expression of MMP23B, involved in the breakdown of the extracellular matrix, and pain intensity, and an inverse relationship between blood cell gene expression of HS6ST1, responsible for 6-O-sulfation of heparan sulfate, and indicators of knee muscular strength. Expression levels of specific genes in blood cells, in particular genes related to GAG metabolism and extracellular matrix dynamics, are potential biomarkers of beneficial effects on articular health.

Mechanoregulation of human articular chondrocyte aggrecan and type II collagen expression by intermittent hydrostatic pressure in vitro.

PubMed

Ikenoue, Takashi; Trindade, Michael C D; Lee, Mel S; Lin, Eric Y; Schurman, David J; Goodman, Stuart B; Smith, R Lane

2003-01-01

This study addressed the hypothesis that duration and magnitude of applied intermittent hydrostatic pressure (IHP) are critical parameters in regulation of normal human articular chondrocyte aggrecan and type II collagen expression. Articular chondrocytes were isolated from knee cartilage and maintained as primary, high-density monolayer cultures. IHP was applied at magnitudes of 1, 5 and 10 MPa at 1 Hz for durations of either 4 h per day for one day (4 x 1) or 4 h per day for four days (4 x 4). Total cellular RNA was isolated and analyzed for aggrecan and type II collagen mRNA signal levels using specific primers and reverse transcription polymerase chain reaction (RT-PCR) nested with beta-actin primers as internal controls. With a 4x1 loading regimen, aggrecan mRNA signal levels increased 1.3- and 1.5-fold at 5 and 10 MPa, respectively, relative to beta-actin mRNA when compared to unloaded cultures. Changing the duration of loading to a 4x4 regimen increased aggrecan mRNA signal levels by 1.4-, 1.8- and 1.9-fold at loads of 1, 5 and 10 MPa, respectively. In contrast to the effects of IHP on aggrecan, type II collagen mRNA signal levels were only upregulated at loads of 5 and 10 MPa with the 4x4 loading regimen. Analysis of cell-associated protein by western blotting confirmed that IHP increased aggrecan and type II collagen in chondrocyte extracts. These data demonstrate that duration and magnitude of applied IHP differentially alter chondrocyte matrix protein expression. The results show that IHP provides an important stimulus for increasing cartilage matrix anabolism and may contribute to repair and regeneration of damaged or diseased cartilage.

Collagen Type IV and Laminin Expressions during Cartilage Repair and in Late Clinically Failed Repair Tissues from Human Subjects

PubMed Central

Foldager, Casper Bindzus; Toh, Wei Seong; Christensen, Bjørn Borsøe; Lind, Martin; Gomoll, Andreas H.; Spector, Myron

2016-01-01

Objective To identify the collagen type IV (Col4) isoform in articular cartilage and to evaluate the expressions of Col4 and laminin in the pericellular matrix (PCM) in damaged cartilage and during cartilage repair. Design The Col4 isoform was determined in chondrocytes isolated from 6 patients cultured up to 6 days and in 21% O2 or 1% O2, and the gene expression of Col4 α-chains was investigated. The distribution of Col4 and laminin in traumatically damaged cartilage (n = 7) and clinically failed cartilage repair (microfracture, TruFit, autologous chondrocyte implantation; n = 11) were investigated using immunohistochemistry. Normal human cartilage was used as control (n = 8). The distribution during clinical cartilage repair procedures was investigated in a minipig model with 6-month follow-up (untreated chondral, untreated osteochondral, microfracture, autologous chondrocyte implantation; n = 10). Results The Col4 isoform in articular cartilage was characterized as α1α1α2, which is an isoform containing antiangiogenic domains in the NC1-terminals (arresten and canstatin). In normal cartilage, laminin and Col4 was exclusively found in the PCM. High amounts (>50%) of Col4 in the PCM significantly decreased in damaged cartilage (P = 0.004) and clinically failed repair tissue (P < 0.001). Laminin was only found with high expression (>50%) in 4/8 of the normal samples, which was not statistically significantly different from damaged cartilage (P = 0.15) or failed cartilage repair (P = 0.054). Conclusions Col4 in cartilage contain antiangiogenic domains and may play a role in the hypoxic environment in articular cartilage. Col4 and laminin was not found in the PCM of damaged and clinically failed repair. PMID:26958317

Physical validation of a patient-specific contact finite element model of the ankle.

PubMed

Anderson, Donald D; Goldsworthy, Jane K; Li, Wendy; James Rudert, M; Tochigi, Yuki; Brown, Thomas D

2007-01-01

A validation study was conducted to determine the extent to which computational ankle contact finite element (FE) results agreed with experimentally measured tibio-talar contact stress. Two cadaver ankles were loaded in separate test sessions, during which ankle contact stresses were measured with a high-resolution (Tekscan) pressure sensor. Corresponding contact FE analyses were subsequently performed for comparison. The agreement was good between FE-computed and experimentally measured mean (3.2% discrepancy for one ankle, 19.3% for the other) and maximum (1.5% and 6.2%) contact stress, as well as for contact area (1.7% and 14.9%). There was also excellent agreement between histograms of fractional areas of cartilage experiencing specific ranges of contact stress. Finally, point-by-point comparisons between the computed and measured contact stress distributions over the articular surface showed substantial agreement, with correlation coefficients of 90% for one ankle and 86% for the other. In the past, general qualitative, but little direct quantitative agreement has been demonstrated with articular joint contact FE models. The methods used for this validation enable formal comparison of computational and experimental results, and open the way for objective statistical measures of regional correlation between FE-computed contact stress distributions from comparison articular joint surfaces (e.g., those from an intact versus those with residual intra-articular fracture incongruity).

CT and MR findings in synovial chondromatosis of the temporo-mandibular joint: our experience and review of literature.

PubMed

Testaverde, Lorenzo; Perrone, Anna; Caporali, Laura; Ermini, Antonella; Izzo, Luciano; D'Angeli, Ilaria; Impara, Luca; Mazza, Dario; Izzo, Paolo; Marini, Mario

2011-06-01

To compare Computed Tomography (CT) and Magnetic Resonance (MR) features and their diagnostic potential in the assessment of Synovial Chondromatosis (SC) of the Temporo-Mandibular Joint (TMJ). Eight patients with symptoms and signs compatible with dysfunctional disorders of the TMJ underwent CT and MR scan. We considered the following parameters: soft tissue involvement (disk included), osteostructural alterations of the joints, loose bodies and intra-articular fluid. These parameters were evaluated separately by two radiologists with a "double blinded method" and then, after agreement, definitive assessment of the parameters was given. CT and MR findings were compared. Histopathological results showed metaplastic synovia in all patients and therefore confirmed diagnosis of SC. MR resulted better than CT in the evaluation of all parameters except the osteostructural alterations of the joints, estimated with more accuracy by CT scan. CT scan is excellent to define bony surfaces of the articular joints and flogistic tissue but it fails in the detection of loose bodies when these are not yet calcified. MR scan therefore is the gold standard when SC is suspected since it can visualize loose bodies at early stage and also evaluate disk condition and eventual extra-articular tissues involvement. The use of T2-weighted images and contrast medium allows identifying intra-articular fluid, estimating its entity and discriminating from sinovial tissue. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

One-step generation of murine embryonic stem cell-derived mesoderm progenitors and chondrocytes in a serum-free monolayer differentiation system.

PubMed

Waese, Elaine Y L; Stanford, William L

2011-01-01

Cartilage defects have limited capacity for repair and are often replaced by fibrocartilage with inferior mechanical properties. To overcome the limitations of artificial joint replacement, high-throughput screens (HTS) could be developed to identify molecules that stimulate differentiation and/or proliferation of articular cartilage for drug therapy or tissue engineering. Currently embryonic stem cells (ESCs) can differentiate into articular cartilage by forming aggregates (embryoid body (EB), pellet, micromass), which are difficult to image. We present a novel, single-step method of generating murine ESC-derived chondrocytes in monolayer cultures under chemically defined conditions. Mesoderm induction was achieved in cultures supplemented with BMP4, activin A, or Wnt3a. Prolonged culture with sustained activin A, TGFβ3, or BMP4 supplementation led to robust chondrogenic induction. A short pulse of activin A or BMP4 also induced chondrogenesis efficiently while Wnt3a acted as a later inducer. Long-term supplementation with activin A or with activin A followed by TGFβ3 promoted articular cartilage formation. Thus, we devised a serum-free (SF) culture system to generate ESC-derived chondrocytes without the establishment of 3D cultures or the aid of cell sorting. Cultures were governed by the same signaling pathways as 3D ESC differentiation systems and limb bud mesenchyme or articular cartilage explant cultures. Copyright © 2010 Elsevier B.V. All rights reserved.

Changes in Muscle and Joint Coordination in Learning to Direct Forces

PubMed Central

Hasson, Christopher J.; Caldwell, Graham E.; van Emmerik, Richard E.A.

2008-01-01

While it has been suggested that biarticular muscles have a specialized role in directing external reaction forces, it is unclear how humans learn to coordinate mono- and bi-articular muscles to perform force-directing tasks. Subjects were asked to direct pedal forces in a specified target direction during one-legged cycling. We expected that with practice, performance improvement would be associated with specific changes in joint torque patterns and mono- and bi-articular muscular coordination. Nine male subjects practiced pedaling an ergometer with only their left leg, and were instructed to always direct their applied pedal force perpendicular to the crank arm (target direction) and to maintain a constant pedaling speed. After a single practice session, the mean error between the applied and target pedal force directions decreased significantly. This improved performance was accompanied by a significant decrease in the amount of ankle angular motion and a smaller increase in knee and hip angular motion. This coincided with a re-organization of lower extremity joint torques, with a decrease in ankle plantarflexor torque and an increase in knee and hip flexor torques. Changes were seen in both mono- and bi-articular muscle activity patterns. The monoarticular muscles exhibited greater alterations, and appeared to contribute to both mechanical work and force directing. With practice, a loosening of the coupling between biarticular thigh muscle activation and joint torque co-regulation was observed. The results demonstrated that subjects were able to learn a complex and dynamic force-directing task by changing the direction of their applied pedal forces through re-organization of joint torque patterns and mono- and bi-articular muscle coordination. PMID:18405988

The histology of tendon attachments to bone in man.

PubMed Central

Benjamin, M; Evans, E J; Copp, L

1986-01-01

Based on a parallel study of a wide range of human tendons from embalmed dissecting room subjects and from a study of dried bones, an explanation is offered for the well known similarity in gross appearance between the markings left by certain tendons (e.g. those of the rotator cuff) and by articular surfaces on dried bones. Epiphyseal tendons leave markings on bones that look like those left by articular surfaces. These tendons have a prominent zone of fibrocartilage at their attachment site and the deepest part of this is calcified, just as the deepest part of articular hyaline cartilage is calcified. After maceration of the soft tissues, the calcified (fibro) cartilage is left attached to the bone at articular surfaces and at the sites of tendon attachment. In all cases, the tissues separate at the basophilic tidemark between the calcified and uncalcified regions. This tidemark is smooth where there is much overlying uncalcified (fibro) cartilage and it is the smoothness that gives the typical appearance of the dried bone. Blood vessels do not generally traverse the tendon fibrocartilage plugs. Hence the areas are devoid of vascular foramina. The functional significance of tendon fibrocartilage is discussed with particular reference to supraspinatus. It is suggested that the uncalcified fibrocartilage ensures that the tendon fibres do not bend, splay out or become compressed at a hard tissue interface, and are thereby offered some protection from wear and tear. It is also suggested that the fibrocartilage plug of supraspinatus prevents the tendon from rubbing on the head of the humerus. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 PMID:3693113

Progressive cell-mediated changes in articular cartilage and bone in mice are initiated by a single session of controlled cyclic compressive loading.

PubMed

Ko, Frank C; Dragomir, Cecilia L; Plumb, Darren A; Hsia, Allison W; Adebayo, Olufunmilayo O; Goldring, Steven R; Wright, Timothy M; Goldring, Mary B; van der Meulen, Marjolein C H

2016-11-01

We previously showed that repetitive cyclic loading of the mouse knee joint causes changes that recapitulate the features of osteoarthritis (OA) in humans. By applying a single loading session, we characterized the temporal progression of the structural and compositional changes in subchondral bone and articular cartilage. We applied loading during a single 5-minute session to the left tibia of adult (26-week-old) C57Bl/6 male mice at a peak load of 9.0N for 1,200 cycles. Knee joints were collected at times 0, 1, and 2 weeks after loading. The changes in articular cartilage and subchondral bone were analyzed by histology, immunohistochemistry (caspase-3 and cathepsin K), and microcomputed tomography. At time 0, no change was evident in chondrocyte viability or cartilage or subchondral bone integrity. However, cartilage pathology demonstrated by localized thinning and proteoglycan loss occurred at 1 and 2 weeks after the single session of loading. Transient cancellous bone loss was evident at 1 week, associated with increased osteoclast number. Bone loss was reversed to control levels at 2 weeks. We observed formation of fibrous and cartilaginous tissues at the joint margins at 1 and 2 weeks. Our findings demonstrate that a single session of noninvasive loading leads to the development of OA-like morphological and cellular alterations in articular cartilage and subchondral bone. The loss in subchondral trabecular bone mass and thickness returns to control levels at 2 weeks, whereas the cartilage thinning and proteoglycan loss persist. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1941-1949, 2016. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Reconstruction of cartilage with clonal mesenchymal stem cell-acellular dermal matrix in cartilage defect model in nonhuman primates.

PubMed

Ma, Anlun; Jiang, Li; Song, Lijun; Hu, Yanxin; Dun, Hao; Daloze, Pierre; Yu, Yonglin; Jiang, Jianyuan; Zafarullah, Muhammad; Chen, Huifang

2013-07-01

Articular cartilage defects are commonly associated with trauma, inflammation and osteoarthritis. Mesenchymal stem cell (MSC)-based therapy is a promising novel approach for repairing articular cartilage. Direct intra-articular injection of uncommitted MSCs does not regenerate high-quality cartilage. This study explored utilization of a new three-dimensional, selected chondrogenic clonal MSC-loaded monkey acellular dermal matrix (MSC-ADM) scaffold to repair damaged cartilage in an experimental model of knee joint cartilage defect in Cynomolgus monkeys. MSCs were characterized for cell size, cell yield, phenotypes, proliferation and chondrogenic differentiation capacity. Chondrogenic differentiation assays were performed at different MSC passages by sulfated glycosaminoglycans (sGAG), collagen, and fluorescence activated cell sorter (FACS) analysis. Selected chondrogenic clonal MSCs were seeded onto ADM scaffold with the sandwich model and MSC-loaded ADM grafts were analyzed by confocal microscopy and scanning electron microscopy. Cartilage defects were treated with normal saline, clonal MSCs and clonal MSC-ADM grafts, respectively. The clinical parameters, and histological and immunohistochemical examinations were evaluated at weeks 8, 16, 24 post-treatment, respectively. Polyclonal and clonal MSCs could differentiate into the chondrogenic lineage after stimulation with suitable chondrogenic factors. They expressed mesenchymal markers and were negative for hematopoietic markers. Articular cartilage defects were considerably improved and repaired by selected chondrogenic clonal MSC-based treatment, particularly, in MSC-ADM-treated group. The histological scores in MSC-ADM-treated group were consistently higher than those of other groups. Our results suggest that selected chondrogenic clonal MSC-loaded ADM grafts could improve the cartilage lesions in Cynomolgus monkey model, which may be applicable for repairing similar human cartilage defects. Copyright © 2013 Elsevier B.V. All rights reserved.

Cadaveric Study of the Articular Branches of the Shoulder Joint.

PubMed

Eckmann, Maxim S; Bickelhaupt, Brittany; Fehl, Jacob; Benfield, Jonathan A; Curley, Jonathan; Rahimi, Ohmid; Nagpal, Ameet S

This cadaveric study investigated the anatomic relationships of the articular branches of the suprascapular (SN), axillary (AN), and lateral pectoral nerves (LPN), which are potential targets for shoulder analgesia. Sixteen embalmed cadavers and 1 unembalmed cadaver, including 33 shoulders total, were dissected. Following dissections, fluoroscopic images were taken to propose an anatomical landmark to be used in shoulder articular branch blockade. Thirty-three shoulders from 17 total cadavers were studied. In a series of 16 shoulders, 16 (100%) of 16 had an intact SN branch innervating the posterior head of the humerus and shoulder capsule. Suprascapular sensory branches coursed laterally from the spinoglenoid notch then toward the glenohumeral joint capsule posteriorly. Axillary nerve articular branches innervated the posterolateral head of the humerus and shoulder capsule in the same 16 (100%) of 16 shoulders. The AN gave branches ascending circumferentially from the quadrangular space to the posterolateral humerus, deep to the deltoid, and inserting at the inferior portion of the posterior joint capsule. In 4 previously dissected and 17 distinct shoulders, intact LPNs could be identified in 14 (67%) of 21 specimens. Of these, 12 (86%) of 14 had articular branches innervating the anterior shoulder joint, and 14 (100%) of 14 LPN articular branches were adjacent to acromial branches of the thoracoacromial blood vessels over the superior aspect of the coracoid process. Articular branches from the SN, AN, and LPN were identified. Articular branches of the SN and AN insert into the capsule overlying the glenohumeral joint posteriorly. Articular branches of the LPN exist and innervate a portion of the anterior shoulder joint.

The effect of intra-articular hyaluronate and tramadol injection on patients with adhesive capsulitis of the shoulder.

PubMed

Kim, Kyung-Hee; Suh, Jung-Woo; Oh, Ki Young

2017-08-03

Local administration of opioids causes effective analgesia without adverse effects related to the central nervous system. After the beneficial demonstration of peripheral opioid receptors in joint synovia, intra-articular opioid injections were used for pain treatment. Clinical studies have reported the safety and efficacy of hyaluronate injection in the shoulder joint of patients with osteoarthritis, periarthritis, rotator cuff tears, and adhesive capsulitis. To estimate the efficacy of intra-articular hyaluronate and tramadol injection for adhesive capsulitis of the shoulder compared with that of intra-articular hyaluronate injection alone. Thirty patients with adhesive capsulitis of the shoulder were randomized to the hyaluronate group (n= 16) or the tramadol group (n= 14). Hyaluronate group members were administered five weekly intra-articular hyaluronate injections; tramadol group members were administered three weekly intra-articular hyaluronate and tramadol injections and then two weekly intra-articular injections of hyaluronate. Visual Analog Scale (VAS), passive range of motion (PROM) of the shoulder joint, and Shoulder Pain and Disability Index (SPADI) scores were assessed at baseline and weeks 1, 2, 3, 4, and 6 after the initial injection. A significant improvement was observed in VAS, PROM, and SPADI scores between time points in both groups. In comparison in both groups at weeks 1 and 2 after the initial injection the VAS scores of the tramadol group were significantly lower than those of the hyaluronate group. Intra-articular hyaluronate with tramadol showed more rapid and strong analgesic effects than intra-articular hyaluronate alone and did not induce any adverse effects.

Combined Intra- and Extra-articular Reconstruction of the Anterior Cruciate Ligament: The Reconstruction of the Knee Anterolateral Ligament

PubMed Central

Helito, Camilo Partezani; Bonadio, Marcelo Batista; Gobbi, Riccardo Gomes; da Mota e Albuquerque, Roberto Freire; Pécora, José Ricardo; Camanho, Gilberto Luis; Demange, Marco Kawamura

2015-01-01

We present a new technique for the combined intra- and extra-articular reconstruction of the anterior cruciate ligament. Intra-articular reconstruction is performed in an outside-in manner according to the precepts of the anatomic femoral tunnel technique. Extra-articular reconstruction is performed with the gracilis tendon while respecting the anatomic parameters of the origin and insertion points and the path described for the knee anterolateral ligament. PMID:26258037

MRI features of cervical articular process degenerative joint disease in Great Dane dogs with cervical spondylomyelopathy.

PubMed

Gutierrez-Quintana, Rodrigo; Penderis, Jacques

2012-01-01

Cervical spondylomyelopathy or Wobbler syndrome commonly affects the cervical vertebral column of Great Dane dogs. Degenerative changes affecting the articular process joints are a frequent finding in these patients; however, the correlation between these changes and other features of cervical spondylomyelopathy are uncertain. We described and graded the degenerative changes evident in the cervical articular process joints from 13 Great Danes dogs with cervical spondylomyelopathy using MR imaging, and evaluated the relationship between individual features of cervical articular process joint degeneration and the presence of spinal cord compression, vertebral foraminal stenosis, intramedullary spinal cord changes, and intervertebral disc degenerative changes. Degenerative changes affecting the articular process joints were common, with only 13 of 94 (14%) having no degenerative changes. The most severe changes were evident between C4-C5 and C7-T1 intervertebral spaces. Reduction or loss of the hyperintense synovial fluid signal on T2-weighted MR images was the most frequent feature associated with articular process joint degenerative changes. Degenerative changes of the articular process joints affecting the synovial fluid or articular surface, or causing lateral hypertrophic tissue, were positively correlated with lateral spinal cord compression and vertebral foraminal stenosis. Dorsal hypertrophic tissue was positively correlated with dorsal spinal cord compression. Disc-associated spinal cord compression was recognized less frequently. © 2011 Veterinary Radiology & Ultrasound.

Recognizing different tissues in human fetal femur cartilage by label-free Raman microspectroscopy

NASA Astrophysics Data System (ADS)

Kunstar, Aliz; Leijten, Jeroen; van Leuveren, Stefan; Hilderink, Janneke; Otto, Cees; van Blitterswijk, Clemens A.; Karperien, Marcel; van Apeldoorn, Aart A.

2012-11-01

Traditionally, the composition of bone and cartilage is determined by standard histological methods. We used Raman microscopy, which provides a molecular "fingerprint" of the investigated sample, to detect differences between the zones in human fetal femur cartilage without the need for additional staining or labeling. Raman area scans were made from the (pre)articular cartilage, resting, proliferative, and hypertrophic zones of growth plate and endochondral bone within human fetal femora. Multivariate data analysis was performed on Raman spectral datasets to construct cluster images with corresponding cluster averages. Cluster analysis resulted in detection of individual chondrocyte spectra that could be separated from cartilage extracellular matrix (ECM) spectra and was verified by comparing cluster images with intensity-based Raman images for the deoxyribonucleic acid/ribonucleic acid (DNA/RNA) band. Specific dendrograms were created using Ward's clustering method, and principal component analysis (PCA) was performed with the separated and averaged Raman spectra of cells and ECM of all measured zones. Overall (dis)similarities between measured zones were effectively visualized on the dendrograms and main spectral differences were revealed by PCA allowing for label-free detection of individual cartilaginous zones and for label-free evaluation of proper cartilaginous matrix formation for future tissue engineering and clinical purposes.

Regeneration of hyaline articular cartilage with irradiated transforming growth factor beta1-producing fibroblasts.

PubMed

Song, Sun U; Hong, Young-Jin; Oh, In-Suk; Yi, Youngsuk; Choi, Kyoung Baek; Lee, Jung Woo; Park, Kwang-Won; Han, Jeoung-Uk; Suh, Jun-Kyu; Lee, Kwan Hee

2004-01-01

The regeneration of hyaline articular cartilage by cell-mediated gene therapy using transforming growth factor beta(1) (TGF-beta(1))-producing fibroblasts (NIH 3T3-TGF-beta(1)) has been reported previously. In this study, we investigated whether TGF-beta(1)-producing fibroblasts irradiated with a lethal dose of radiation are still capable of inducing the regeneration of hyaline articular cartilage. NIH 3T3TGF-beta(1) fibroblasts were exposed to doses of 20, 40, or 80 Gy, using a irradiator, and then injected into artificially made partial defects on the femoral condyle of rabbit knee joints. The rabbits were killed 3 or 6 weeks postinjection and hyaline articular cartilage regeneration was evaluated by histological and immunohistochemical staining (n = 5 per each group). Irradiated NIH 3T3-TGFbeta(1) fibroblasts started to die rapidly 3 days after irradiation; moreover, the kinetics of their viability were similar regardless of the radiation intensity. TGF-beta1 expression, measured by ELISA, showed that the TGF-beta(1) protein produced from the irradiated cells peaked 5 days after irradiation and thereafter declined rapidly. Complete filling of the defect with reparative tissue occurred in all the groups, although variations were observed in terms of the nature of the repair tissue. Histological and immunohistochemical staining of the repair tissue showed that the tissue newly formed by irradiated NIH 3T3-TGF-beta(1) fibroblasts after exposure to 20 Gy had hyaline cartilage-like characteristics, as was observed in the nonirradiated controls. On the other hand, the repair tissue formed by NIH 3T3-TGF-beta(1) fibroblasts irradiated with 40 or 80 Gy showed more fibrous cartilage-like tissue. These results suggest that TGF-beta(1)-producing fibroblasts irradiated up to a certain level of lethal dose (i.e., 20 Gy) are able to induce normal-appearing articular cartilage in vivo. Therefore, irradiated heterologous cell-mediated TGF-beta(1) gene therapy may be clinically useful and an efficient method of regenerating hyaline articular cartilage.

The Clinical Utility and Diagnostic Performance of MRI for Identification of Early and Advanced Knee Osteoarthritis: A Systematic Review

PubMed Central

Quatman, Carmen E.; Hettrich, Carolyn M.; Schmitt, Laura C.; Spindler, Kurt P.

2013-01-01

Background Current diagnostic strategies for detection of structural articular cartilage abnormalities, the earliest structural signs of osteoarthritis, often do not capture the condition until it is too far advanced for the most potential benefit of non-invasive interventions. Purpose Systematically review the literature relative to the following questions: (1) Is MRI a valid, sensitive, specific, accurate and reliable instrument to identify knee articular cartilage abnormalities compared to arthroscopy? (2) Is MRI a sensitive tool that can be utilized to identify early cartilage degeneration? Study Design Systematic Review Methods A systematic search was performed in November 2010 using PubMed MEDLINE (from 1966), CINAHL (from 1982), SPORTDiscus (from 1985), and SCOPUS (from 1996) databases. Results Fourteen level I and 13 level II studies were identified that met inclusion criteria and provided information related to diagnostic performance of MRI compared to arthroscopic evaluation. The diagnostic performance of MRI demonstrated a large range of sensitivities, specificities, and accuracies. The sensitivity for identifying articular cartilage abnormalities in the knee joint was reported between 26–96%. Specificity and accuracy was reported between 50–100% and 49–94%, respectively. The sensitivity, specificity, and accuracy for identifying early osteoarthritis were reported between 0–86%, 48–95%, and 5–94%, respectively. As a result of inconsistencies between imaging techniques and methodological shortcomings of many of the studies, a meta-analysis was not performed and it was difficult to fully synthesize the information to state firm conclusions about the diagnostic performance of MRI. Conclusions There is evidence in some MRI protocols that MRI is a relatively valid, sensitive, specific, accurate, and reliable clinical tool for identifying articular cartilage degeneration. Due to heterogeneity of MRI sequences it is not possible to make definitive conclusions regarding its global clinical utility for guiding diagnosis and treatment strategies. Clinical Relevance Traumatic sports injuries to the knee may be significant precursor events to early onset of posttraumatic osteoarthritis. MRI may aid in early identification of structural injuries to articular cartilage as evidenced by articular cartilage degeneration grading. PMID:21730207

Intra-articular findings in symptomatic minor instability of the lateral elbow (SMILE).

PubMed

Arrigoni, Paolo; Cucchi, Davide; D'Ambrosi, Riccardo; Butt, Usman; Safran, Marc R; Denard, Patrick; Randelli, Pietro

2017-07-01

Lateral epicondylitis is generally considered an extra-articular condition. The role of minor instability in the aetiology of lateral elbow pain has rarely been considered. The aim of this study was to evaluate the correlation of lateral ligamentous laxity with aspects of intra-articular lateral elbow pathology and investigate the role of minor instability in lateral elbow pain. Thirty-five consecutive patients aged between 20 and 60 years with recalcitrant lateral epicondylitis who had failed conservative therapy and had no previous trauma or overt instability, were included. The presence of three signs of lateral ligamentous patholaxity and five intra-articular findings were documented during arthroscopy. The relative incidence of each of these was calculated, and the correlation between patholaxity and intra-articular pathology was evaluated. At least one sign of lateral ligamentous laxity was observed in 48.6% of the studied cohort, and 85.7% demonstrated at least one intra-articular abnormal finding. Radial head ballottement was the most common sign of patholaxity (42.9%). Synovitis was the most common intra-articular aspect of pathology (77.1%), followed by lateral capitellar chondropathy (40.0%). A significant correlation was found between the presence of lateral ligamentous patholaxity signs and capitellar chondropathy (p = 0.0409), as well as anteromedial synovitis (p = 0.0408). Almost one half of patients suffering from recalcitrant lateral epicondylitis display signs of lateral ligamentous patholaxity, and over 85% demonstrate at least one intra-articular abnormality. The most frequent intra-articular findings are synovitis and lateral capitellar chondropathy, which correlate significantly with the presence of lateral ligamentous patholaxity. The fact that several patients demonstrated multiple intra-articular findings in relation to laxity provides support to a sequence of pathologic changes that may result from a symptomatic minor instability of the lateral elbow (SMILE) condition. III.

Rehabilitation after Articular Cartilage Repair of the Knee in the Football (Soccer) Player

PubMed Central

Silvers, Holly Jacinda; Steinwachs, Matthias

2012-01-01

Background: Participation in football can put both male and female players at an increased risk for knee osteoarthritis. There is a higher prevalence of focal chondral defects in the knee of athletes compared to nonathletes. The management of chondral defects in the football player is complex and multifactorial. Objective: The aim of this study is to provide an overview of the current strategies for rehabilitation after articular cartilage repair of the knee in the football player. Design: A review of current literature and the scientific evidence for rehabilitation after articular cartilage repair of the knee. Conclusions: Articular cartilage repair has been shown to allow return to sport but rehabilitation timescales are lengthy. Successful rehabilitation for a return to football after articular cartilage repair of the knee requires the player to be able to accept the load of the sport. This necessitates a multidisciplinary approach to rehabilitation, especially in the transition from therapy to performance care. It should be recognized that not all players will return to football after articular cartilage repair. The evidence base for rehabilitative practice after articular cartilage repair is increasing but remains sparse in areas. PMID:26069608

Articular manifestations in patients with Lyme disease.

PubMed

Vázquez-López, María Esther; Díez-Morrondo, Carolina; Sánchez-Andrade, Amalia; Pego-Reigosa, Robustiano; Díaz, Pablo; Castro-Gago, Manuel

To determine the percentage of Lyme patients with articular manifestations in NW Spain and to know their evolution and response to treatment. A retrospective study (2006-2013) was performed using medical histories of confirmed cases of Lyme disease showing articular manifestations. Clinical and laboratory characteristics, together with the treatment and evolution of the patients, were analysed. Seventeen out of 108 LD confirmed patients (15.7%) showed articular manifestations. Regarding those 17 patients, 64.7%, 29.4% and 5.9% presented arthritis, arthralgia and bursitis, respectively. The knee was the most affected joint. Articular manifestations were often associated to neurological, dermatological and cardiac pathologies. Otherwise, most patients were in Stage III. The 11.8% of the cases progressed to a recurrent chronic arthritis despite the administration of an appropriate treatment. Lyme disease patients showing articular manifestations should be included in the diagnosis of articular affections in areas of high risk of hard tick bite, in order to establish a suitable and early treatment and to avoid sequels. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Treatment strategy for sacroiliac joint-related pain at or around the posterior superior iliac spine.

PubMed

Murakami, Eiichi; Kurosawa, Daisuke; Aizawa, Toshimi

2018-02-01

Pain at or around the posterior superior iliac spine (PSIS) is characteristic of sacroiliac joint (SIJ) -related pain. This pain can be treated by either a peri- or intra-articular injection into the joint, with the former being much easier to perform. We investigated whether peri- or intra-articular injections were more frequently effective in patients with SIJ-related pain, and aimed to create an efficient treatment strategy for SIJ-related pain at or around the PSIS. Prospective case-control study. We evaluated 85 patients with pain at or around the posterior superior iliac spine as indicated by the one finger test. First, we performed a peri-articular sacroiliac joint injection. If it was ineffective, an intra-articular injection was later given. Groin pain, sitting pain, sacroiliac joint shear test results, and posterior superior iliac spine and sacro-tuberous ligament tenderness were also compared between patients for whom a peri- or intra-articular injection was effective. Seventy-two (85%) of 85 patients had an effective injection. Out of these 72 patients, 58 (81%) had a positive peri-articular injection and 14 (19%) had a positive intra-articular injection. Four items, excluding tenderness of the sacro-tuberous ligament had no significant difference between these two injection types. To treat sacroiliac joint-related pain at or around the posterior superior iliac spine, a peri-articular injection should be performed first, and only if it is not effective should an intra-articular injection be administered. Using this strategy, we expect that most patients with sacroiliac joint-related pain will be efficiently diagnosed and treated. Copyright © 2017 Elsevier B.V. All rights reserved.

Is there a place for intra-articular hyaluronate in osteoarthritis of the knee?

PubMed

Kirwan, J

2001-06-01

Viscosupplementation refers to the intra-articular injection of hyaluronic acid (HA) as a hyaluronate to relieve pain and improve function, usually in patients with knee OA. HA is the major constituent of a 1-2-micron layer on the surface of articular cartilage as well as a major constituent of synovial fluid (SF). Solutions of HA can act as lubricants when movements are slow and as shock absorbers when movements are fast. In arthritis, the molecular weight of HA is reduced, and so are its properties. Viscosupplementation has been advocated as a way of reversing this, but intra-articular HA has other properties, such as an anti-inflammatory effect, which may also contribute to any therapeutic effect. There is a large placebo effect from intra-articular injections, and the benefits of intra-articular glucocorticoids may be only slightly better than this effect. In only one randomised, placebo-controlled trial was the difference in response significant. Studies of intra-articular HA also show a marked placebo response (where it has been measured), but some have suggested a measurable benefit, which may be more prolonged that that of glucocorticoids. There is only a single study in which the effects of intra-articular therapy with placebo, glucocorticoids and viscosupplementation can be compared. Here, HA may have had a slightly longer period of benefit than triamcinolone hexacetonide or placebo. The very large placebo response after aspiration of the knee may seriously mislead those engaged in uncontrolled therapeutic evaluation of intra-articular therapy. Current evidence suggests that viscosupplements probably provide a similar level of pain relief to glucocorticoids and do so for several months, but the onset is slower, and there is the potential for local adverse reactions.

Interaction of Electromagnetic Fields with Biosynthetic Processes in Connective Tissue Cells

DTIC Science & Technology

1989-12-01

Normal Chondrocytes.............................................10 Swarm Rat Chondrosarcoma Cells..................................15 Conclusions...articular cartilage, and in rat chondrosarcoma cells (a continuous cell line). Another long-term goal is to study the possible role of fields in...Investigators have recently found that bovine [12, 13, 14], rabbit [15], and human [161 chondrocytes as well as Swarm rat chondrosarcoma cells [171 isolated a

High-resolution measurements of the multilayer ultra-structure of articular cartilage and their translational potential

PubMed Central

2014-01-01

Current musculoskeletal imaging techniques usually target the macro-morphology of articular cartilage or use histological analysis. These techniques are able to reveal advanced osteoarthritic changes in articular cartilage but fail to give detailed information to distinguish early osteoarthritis from healthy cartilage, and this necessitates high-resolution imaging techniques measuring cells and the extracellular matrix within the multilayer structure of articular cartilage. This review provides a comprehensive exploration of the cellular components and extracellular matrix of articular cartilage as well as high-resolution imaging techniques, including magnetic resonance image, electron microscopy, confocal laser scanning microscopy, second harmonic generation microscopy, and laser scanning confocal arthroscopy, in the measurement of multilayer ultra-structures of articular cartilage. This review also provides an overview for micro-structural analysis of the main components of normal or osteoarthritic cartilage and discusses the potential and challenges associated with developing non-invasive high-resolution imaging techniques for both research and clinical diagnosis of early to late osteoarthritis. PMID:24946278

Relationships Between Quantitative Pulse-Echo Ultrasound Parameters from the Superficial Zone of the Human Articular Cartilage and Changes in Surface Roughness, Collagen Content or Collagen Orientation Caused by Early Degeneration.

PubMed

Kiyan, Wataru; Ito, Akira; Nakagawa, Yasuaki; Mukai, Shogo; Mori, Koji; Arai, Tatsuo; Uchino, Eiichiro; Okuno, Yasushi; Kuroki, Hiroshi

2017-08-01

We aimed to quantitatively investigate the relationship between amplitude-based pulse-echo ultrasound parameters and early degeneration of the knee articular cartilage. Twenty samples from six human femoral condyles judged as grade 0 or 1 according to International Cartilage Repair Society grading were assessed using a 15-MHz pulsed-ultrasound 3-D scanning system ex vivo. Surface roughness (R q ), average collagen content (A 1 ) and collagen orientation (A 12 ) in the superficial zone of the cartilage were measured via laser microscopy and Fourier transform infrared imaging spectroscopy. Multiple regression analysis with a linear mixed-effects model (LMM) revealed that a time-domain reflection coefficient at the cartilage surface (R c ) had a significant coefficient of determination with R q and A 12 (R LMMm 2 =0.79); however, R c did not correlate with A 1 . Concerning the collagen characteristic in the superficial zone, R c was found to be a sensitive indicator reflecting collagen disorganization, not collagen content, for the early degeneration samples. Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Development of gait training system powered by pneumatic actuator like human musculoskeletal system.

PubMed

Yamamoto, Shin-ichiroh; Shibata, Yoshiyuki; Imai, Shingo; Nobutomo, Tatsuya; Miyoshi, Tasuku

2011-01-01

The purpose of this study was to develop a body weight support gait training system for stroke and spinal cord injury (SCI) patient. This system consists of an orthosis powered by pneumatic McKibben actuators and a piece of equipment of body weight support. The attachment of powered orthosis can be fit to individual subjects with different body size. This powered orthosis is driven by pneumatic McKibben actuators arranged as a pair of agonistic and antagonistic bi-articular muscle models and two pairs of agonistic and antagonistic mono-articular muscle models like the human musculoskeletal system. The body weight support equipment suspends the subject's body in a wire harness, with the body weight is supported continuously by a counterweight. The powered orthosis is attached to the body weight support equipment by a parallel linkage, and its movement of powered orthosis is limited at the sagittal plane. The weight of the powered orthosis is compensated by a parallel linkage with a gas-spring. In this paper, we report the detailed mechanics of this body weight support gait training system and the results of several experiments for evaluating the system. © 2011 IEEE

"Lucy" (A.L. 288-1) had five sacral vertebrae.

PubMed

Russo, Gabrielle A; Williams, Scott A

2015-02-01

A "long-backed" scenario of hominin vertebral evolution posits that early hominins possessed six lumbar vertebrae coupled with a high frequency of four sacral vertebrae (7:12-13:6:4), a configuration acquired from a hominin-panin last common ancestor (PLCA) having a vertebral formula of 7:13:6-7:4. One founding line of evidence for this hypothesis is the recent assertion that the "Lucy" sacrum (A.L. 288-1an, Australopithecus afarensis) consists of four sacral vertebrae and a partially-fused first coccygeal vertebra (Co1), rather than five sacral vertebrae as in modern humans. This study reassesses the number of sacral vertebrae in Lucy by reexamining the distal end of A.L.288-1an in the context of a comparative sample of modern human sacra and Co1 vertebrae, and the sacrum of A. sediba (MH2). Results demonstrate that, similar to S5 in modern humans and A. sediba, the last vertebra in A.L. 288-1an exhibits inferiorly-projecting (right side) cornua and a kidney-shaped inferior body articular surface. This morphology is inconsistent with that of fused or isolated Co1 vertebrae in humans, which either lack cornua or possess only superiorly-projecting cornua, and have more circularly-shaped inferior body articular surfaces. The level at which the hiatus' apex is located is also more compatible with typical five-element modern human sacra and A. sediba than if only four sacral vertebrae are present. Our observations suggest that A.L. 288-1 possessed five sacral vertebrae as in modern humans; thus, sacral number in "Lucy" does not indicate a directional change in vertebral count that can provide information on the PLCA ancestral condition. © 2015 Wiley Periodicals, Inc.

Symposium: evidence for the use of intra-articular cortisone or hyaluronic acid injection in the hip

PubMed Central

Chandrasekaran, Sivashankar; Lodhia, Parth; Suarez-Ahedo, Carlos; Vemula, S. Pavan; Martin, Timothy J.; Domb, Benjamin G.

2016-01-01

The primary purpose of this review article is to discuss the role of diagnostic, corticosteroid, hyaluronic acid (HA) and platelet rich plasma (PRP) in the treatment of osteoarthritis (OA) and femoroacetabular impingement (FIA). These treatments play an important biological role in the non-operative management of these conditions. Two independent reviewers performed an search of PubMed for articles that contained at least one of the following search terms pertaining to intra-articular hip injection—local anaesthetic, diagnostic, ultrasound, fluoroscopic, image guided, corticosteroid, HA, PRP, OA, labral tears and FAI. Seventy-two full text articles were suitable for inclusion. There were 18 articles addressing the efficacy of diagnostic intra-articular hip injections. With respect to efficacy in OA there were 25 articles pertaining to efficacy of corticosteroid, 22 of HA and 4 of PRP. There were three articles addressing the efficacy of biologics in FAI. Diagnostic intra-articular hip injections are sensitive and specific for differentiating between intra-articular, extra-articular and spinal causes of hip symptoms. Ultrasound and fluoroscopy improves the precision of intra-articular positioning of diagnostic injections. Corticosteroids are more effective than HA and PRP in alleviating pain from hip OA. A higher dose of corticosteroids produces a longer benefit but volume of injection has no significant effect. Intra-articular corticosteroids do not increase infection rates of subsequent arthroplasty. There is currently limited evidence to warrant the routine use of therapeutic injections in the management of labral tears and FIA. PMID:27026814

Chondrocalcinosis of the hyaline cartilage of the knee: MRI manifestations.

PubMed

Beltran, J; Marty-Delfaut, E; Bencardino, J; Rosenberg, Z S; Steiner, G; Aparisi, F; Padrón, M

1998-07-01

To determine the ability of MRI to detect the presence of crystals of calcium pyrophosphate in the articular cartilage of the knee. The MR studies of 12 knees (11 cases) were reviewed retrospectively and correlated with radiographs (12 cases) and the findings at arthroscopy (2 cases) and surgery (1 case). A total of 72 articular surfaces were evaluated. Radiographic, surgical or arthroscopic demonstration of chondrocalcinosis was used as the gold standard. Additionally, two fragments of the knee of a patient who underwent total knee replacement and demonstrated extensive chondrocalcinosis were studied with radiography and MRI using spin-echo T1-, T2- and proton-density-weighted images as well as two- and three-dimensional fat saturation (2D and 3D Fat Sat) gradient recalled echo (GRE) and STIR sequences. MRI revealed multiple hypointense foci within the articular cartilage in 34 articular surfaces, better shown on 2D and 3D GRE sequences. Radiographs showed 12 articular surfaces with chondrocalcinosis. In three cases with arthroscopic or surgical correlation, MRI demonstrated more diffuse involvement of the articular cartilage than did the radiographs. The 3D Fat Sat GRE sequences were the best for demonstrating articular calcification in vitro. In no case was meniscal calcification identified with MRI. Hyperintense halos around some of the calcifications were seen on the MR images. MRI can depict articular cartilage calcification as hypointense foci using GRE techniques. Differential diagnosis includes loose bodies, post-surgical changes, marginal osteophytes and hemosiderin deposition.

Juxta-articular myxoma and intramuscular myxoma are two distinct entities. Activating Gs alpha mutation at Arg 201 codon does not occur in juxta-articular myxoma.

PubMed

Okamoto, Sumika; Hisaoka, Masanori; Meis-Kindblom, Jeanne M; Kindblom, Lars-Gunnar; Hashimoto, Hiroshi

2002-01-01

Juxta-articular myxoma is a rare myxoid tumor of soft tissue that bears a close histologic resemblance to intramuscular myxoma but is distinguished from the latter by its clinical setting and behavior. Activating missense mutations at the Arg 201 codon of the Gs alpha gene ultimately leading to increased levels of cyclic adenosine monophosphate have been implicated in McCune-Albright syndrome and sporadic fibrous dysplasia of bone. Recently, we have demonstrated that the same Gs alpha mutations occur in intramuscular myxomas associated with fibrous dysplasia of bone (Mazabraud's syndrome) as well as in sporadic intramuscular myxoma. The overlapping histologic appearances of juxta-articular myxoma and intramuscular myxoma prompted us to investigate whether there is a relationship between the two entities. We studied this possibility by looking for Gs alpha mutations in juxta-articular myxoma using polymerase chain reaction (PCR) to amplify appropriate genomic DNA fragments extracted from formalin-fixed, paraffin-embedded specimens of five juxta-articular myxomas, followed by single-strand conformation polymorphism analysis. Using these techniques, no aberrant bands were detected in any of the five juxta-articular myxomas, indicating that they lack Gs alpha mutations. Moreover, DNA sequencing of the PCR products of two JAMs showed no abnormalities. We conclude that juxta-articular myxomas, in contrast to intramuscular myxomas, do not involve Arg 201 mutations of the Gs alpha gene, indicating that they represent distinct entities with different underlying molecular mechanisms.

Particulated articular cartilage: CAIS and DeNovo NT.

PubMed

Farr, Jack; Cole, Brian J; Sherman, Seth; Karas, Vasili

2012-03-01

Cartilage Autograft Implantation System (CAIS; DePuy/Mitek, Raynham, MA) and DeNovo Natural Tissue (NT; ISTO, St. Louis, MO) are novel treatment options for focal articular cartilage defects in the knee. These methods involve the implantation of particulated articular cartilage from either autograft or juvenile allograft donor, respectively. In the laboratory and in animal models, both CAIS and DeNovo NT have demonstrated the ability of the transplanted cartilage cells to "escape" from the extracellular matrix, migrate, multiply, and form a new hyaline-like cartilage tissue matrix that integrates with the surrounding host tissue. In clinical practice, the technique for both CAIS and DeNovo NT is straightforward, requiring only a single surgery to affect cartilage repair. Clinical experience is limited, with short-term studies demonstrating both procedures to be safe, feasible, and effective, with improvements in subjective patient scores, and with magnetic resonance imaging evidence of good defect fill. While these treatment options appear promising, prospective randomized controlled studies are necessary to refine the indications and contraindications for both CAIS and DeNovo NT.

Relevant aspects of imaging in the diagnosis and management of gout.

PubMed

De Avila Fernandes, Eloy; Bergamaschi, Samuel Brighenti; Rodrigues, Tatiane Cantarelli; Dias, Gustavo Coelho; Malmann, Ralff; Ramos, Germano Martins; Monteiro, Soraya Silveira

Gout is an inflammatory arthritis characterized by the deposition of monosodium urate crystals in the synovial membrane, articular cartilage and periarticular tissues leading to inflammation. Men are more commonly affected, mainly after the 5th decade of life. Its incidence has been growing with the population aging. In the majority of the cases, the diagnosis is made by clinical criteria and synovial fluid analysis, in search for monosodium urate crystals. Nonetheless, gout may sometimes have atypical presentations, complicating the diagnosis. In these situations, imaging methods have a fundamental role, aiding in the diagnostic confirmation or excluding other possible differential diagnosis. Conventional radiographs are still the most commonly used method in gout patients' evaluation; nevertheless, this is not a sensitive method, since it detect only late alterations. In the last years, there have been several advances in imaging methods for gout patients. Ultrasound has shown a great accuracy in the diagnosis of gout, identifying monosodium urate deposits in the synovial membrane and articular cartilage, in detecting and characterizing tophi and in identifying tophaceous tendinopathy and enthesopathy. Ultrasound has also been able to show crystal deposition in patients with articular pain in the absence of a classical gout crisis. Computed tomography is an excellent method for detecting bone erosions, being useful in spine involvement. Dual-energy CT is a new method able to provide information about the chemical composition of tissues, with high accuracy in the identification of monosodium urate deposits, even in the early stages of the disease and in cases of difficult characterization. Magnetic resonance imaging is useful in the evaluation of deep tissues not accessible by ultrasound. Besides the diagnosis, with the emergence of new drugs that aim to reduce tophaceous burden, imaging methods have become useful tools in monitoring the treatment of patients with gout. Copyright © 2016. Published by Elsevier Editora Ltda.

Coculture of human mesenchymal stem cells and articular chondrocytes reduces hypertrophy and enhances functional properties of engineered cartilage.

PubMed

Bian, Liming; Zhai, David Y; Mauck, Robert L; Burdick, Jason A

2011-04-01

Mesenchymal stem cells (MSCs) are being recognized as a viable cell source for cartilage repair; however, it still remains a challenge to recapitulate the functional properties of native articular cartilage using only MSCs. Additionally, MSCs may exhibit a hypertrophic phenotype under chondrogenic induction, resulting in calcification after ectopic transplantation. With this in mind, the objective of this study was to assess whether the addition of chondrocytes to MSC cultures influences the properties of tissue-engineered cartilage and MSC hypertrophy when cultured in hyaluronic acid hydrogels. Mixed cell populations (human MSCs and human chondrocytes at a ratio of 4:1) were encapsulated in the hydrogels and exhibited significantly higher Young's moduli, dynamic moduli, glycosaminoglycan levels, and collagen content than did constructs seeded with only MSCs or chondrocytes. Furthermore, the deposition of collagen X, a marker of MSC hypertrophy, was significantly lower in the coculture constructs than in the constructs seeded with MSCs alone. When MSCs and chondrocytes were cultured in distinct gels, but in the same wells, there was no improvement in biomechanical and biochemical properties of the engineered tissue, implying that a close proximity is essential. This approach can be used to improve the properties and prevent calcification of engineered cartilage formed from MSC-seeded hydrogels with the addition of lower fractions of chondrocytes, leading to improved clinical outcomes.

Recapitulation of physiological spatiotemporal signals promotes in vitro formation of phenotypically stable human articular cartilage

PubMed Central

Wei, Yiyong; Zhou, Bin; Bernhard, Jonathan; Robinson, Samuel; Burapachaisri, Aonnicha; Guo, X. Edward

2017-01-01

Standard isotropic culture fails to recapitulate the spatiotemporal gradients present during native development. Cartilage grown from human mesenchymal stem cells (hMSCs) is poorly organized and unstable in vivo. We report that human cartilage with physiologic organization and in vivo stability can be grown in vitro from self-assembling hMSCs by implementing spatiotemporal regulation during induction. Self-assembling hMSCs formed cartilage discs in Transwell inserts following isotropic chondrogenic induction with transforming growth factor β to set up a dual-compartment culture. Following a switch in the basal compartment to a hypertrophic regimen with thyroxine, the cartilage discs underwent progressive deep-zone hypertrophy and mineralization. Concurrent chondrogenic induction in the apical compartment enabled the maintenance of functional and hyaline cartilage. Cartilage homeostasis, chondrocyte maturation, and terminal differentiation markers were all up-regulated versus isotropic control groups. We assessed the in vivo stability of the cartilage formed under different induction regimens. Cartilage formed under spatiotemporal regulation in vitro resisted endochondral ossification, retained the expression of cartilage markers, and remained organized following s.c. implantation in immunocompromised mice. In contrast, the isotropic control groups underwent endochondral ossification. Cartilage formed from hMSCs remained stable and organized in vivo. Spatiotemporal regulation during induction in vitro recapitulated some aspects of native cartilage development, and potentiated the maturation of self-assembling hMSCs into stable and organized cartilage resembling the native articular cartilage. PMID:28228529

Histochemistry as a Unique Approach for Investigating Normal and Osteoarthritic Cartilage

PubMed Central

Musumeci, G.; Castrogiovanni, P.; Mazzone, V.; Szychlinska, M. A.; Castorina, S.; Loreto, C.

2014-01-01

In this review article, we describe benefits and disadvantages of the established histochemical methods for studying articular cartilage tissue under normal, pathological and experimental conditions. We illustrate the current knowledge on cartilage tissue based on histological and immunohistochemical aspects, and in conclusion we provide a short overview on the degeneration of cartilage, such as osteoarthritis. Adult articular cartilage has low capacity to repair itself, and thus even minor injuries may lead to progressive damage and osteoarthritic joint degeneration, resulting in significant pain and disability. Numerous efforts have been made to implement the knowledge in the study of cartilage in the last years, and histochemistry proved to be an especially powerful tool to this aim. PMID:24998926

Label-free characterization of degenerative changes in articular cartilage by Raman spectroscopy

NASA Astrophysics Data System (ADS)

Oshima, Yusuke; Akehi, Mayu; Kiyomatsu, Hiroshi; Miura, Hiromasa

2017-04-01

Osteoarthritis (OA) is very common joint disease in the aging population. Main symptom of OA is accompanied by degenerative changes of articular cartilage. Raman spectroscopy is a label-free technique which enables to analyze molecular composition in degenerative cartilage. We generated an animal OA model surgically induced by knee joint instability and performed Raman spectroscopic analysis for the articular cartilage. In the result, Raman spectral data of the articular cartilage showed drastic changes in comparison between OA and control side. The relative intensity of phosphate band increases in the degenerative cartilage.

Supporting Biomaterials for Articular Cartilage Repair

PubMed Central

Duarte Campos, Daniela Filipa; Drescher, Wolf; Rath, Björn; Tingart, Markus

2012-01-01

Orthopedic surgeons and researchers worldwide are continuously faced with the challenge of regenerating articular cartilage defects. However, until now, it has not been possible to completely mimic the biological and biochemical properties of articular cartilage using current research and development approaches. In this review, biomaterials previously used for articular cartilage repair research are addressed. Furthermore, a brief discussion of the state of the art of current cell printing procedures mimicking native cartilage is offered in light of their use as future alternatives for cartilage tissue engineering. Inkjet cell printing, controlled deposition cell printing tools, and laser cell printing are cutting-edge techniques in this context. The development of mimetic hydrogels with specific biological properties relevant to articular cartilage native tissue will support the development of improved, functional, and novel engineered tissue for clinical application. PMID:26069634

Low-Cost Intra-Articular Distraction Technique Using Kirschner Wires and a Toothed Lamina Spreader.

PubMed

Shymon, Stephen Joseph; Harris, Thomas Gregory

We describe a low-cost (instrument cost) technique for joint distraction using 2 Kirschner wires and a toothed lamina spreader in lieu of a Hintermann distractor. The described technique allows for temporary intra-articular distraction and visualization and preservation of the articular surface with extra-articular instrumentation. The technique can also allow for closed reduction and percutaneous treatment in cases of soft tissue compromise. Additionally, the technique uses common orthopedic surgical instruments, leading to a minimal learning curve for novice surgeons. We have found this distraction technique to be most effective for intra-articular preparation of hindfoot and midfoot arthrodeses and for navicular fracture reduction. Copyright © 2016 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

Articular manifestations of familial hypercholesterolaemia.

PubMed Central

Mathon, G; Gagné, C; Brun, D; Lupien, P J; Moorjani, S

1985-01-01

Familial hypercholesterolaemia is characterised by a decreased removal of low density lipoproteins and premature coronary artery disease. Tendinous xanthomata are a hallmark of the disease. The affected joints may also be the sites of inflammation and pain. Arthropathy has been associated mainly with the homozygous form of familial hypercholesterolaemia, but it is also known to occur in the heterozygous form. We report on the articular manifestations in 73 patients with heterozygous familial hypercholesterolaemia. About 40% of these patients had at least one episode of articular symptoms. The observed articular manifestations may be classified into four types: Achilles pain (18%), Achilles tendinitis (11%), oligoarticular arthritis (7%), polyarticular or rheumatic fever-like arthritis (4%). It is concluded that in heterozygous familial hypercholesterolaemia articular manifestations are frequent, diverse, and may be the first symptom of this metabolic disorder. Images PMID:4037885

Atypical location of an osteoid osteoma with atypical anterior knee pain

PubMed Central

Harun, Mutlu; Hayrettin, Yaldız; Serhat, Mutlu; Engin, Cetinkaya; Kamil, Cepni; Armagan, Arslan; Sancar, Parmaksızoglu Atilla

2014-01-01

INTRODUCTION An osteoid osteoma is a painful tumor that most commonly affects the extra-articular parts of the long bones. An intra-articular location of an osteoid osteoma is rare. Various differential diagnoses may arise in connection with such an unusual location because it causes atypical clinical signs. PRESENTATION OF CASE A 24-year-old male developed pain in the central region of the right knee. Magnetic resonance imaging (MRI) showed no clear pathology in the knee joint. A technetium bone scan and computed tomography (CT) were then ordered and confirmed the presence of an osteoid osteoma in the knee joint. The patient was treated through an anteromedial approach to the knee, and the lesion was removed by excisional biopsy under fluoroscopy. DISCUSSION The diagnosis of intra-articular osteoid osteoma is challenging because the clinical presentation can be misleading. MRI is often requested as the first imaging method when dealing with knee symptoms, and radiologists are often unaware of the clinical presentation. Edema seen on MRI can be misleading with respect to the location of the nidus. CT is considered to be the best imaging method because it usually allows for clear visualization of the nidus. Different treatments have been proposed, ranging from open excision to arthroscopic resection. CONCLUSION Osteoid osteoma should be considered in young adult patients with chronic knee pain and no history of trauma. PMID:25462055

Load distribution of articular cartilage from MR-images by neural nets.

PubMed

Seidel, Peter; Hanke, Göran; Gründer, Wilfried

2005-01-01

Artificial neural nets were used to determine the Young's modulus and spatial load distribution in articular cartilage by means of T2-weighted MR imaging. MR images were obtained in vitro (ex vivo?) from the joints of sheep of different ages (3 months, 9 months, 15 months, 1.5 years, 5 years, 5.5 years) and pigs (4 and 6 months) with a Bruker AMX 300 (7 T) spectrometer equipped with a micro-imaging unit. The knee of a 29-year-old male volunteer was studied in vivo under mechanical load using a clinical Siemens Vision MRT (1.5 T). The load of the cartilage is understood as a non-linear image transformation of loaded versus unloaded images. The artificial neural net was used to recognize given reference pixels of the unloaded cartilage within the image of the loaded cartilage. The Young's modulus was calculated from the local strain and the external pressure using the Hooke's law. With this method, the average Young's modulus was obtained in relationship to the biological age of the cartilage. The investigated age interval showed a progressive increase of 0.5 +/- 0.3 MPa per year. These results are consistent with published results. As shown in this pilot study, the method of neural nets allows the visualization of the spatial load distribution within the articular cartilage.

Lactoferrin from Camelus dromedarius Inhibits Nuclear Transcription Factor-kappa B Activation, Cyclooxygenase-2 Expression and Prostaglandin E2 Production in Stimulated Human Chondrocytes

PubMed Central

Rasheed, Naila; Alghasham, Abdullah; Rasheed, Zafar

2016-01-01

Background: Osteoarthritis (OA) is a progressive joint disorder, which remains the leading cause of chronic disability in aged people. Nuclear factor-kappa B (NF)-κB is a major cellular event in OA and its activation by interleukin-1β (IL-1β) plays a critical role in cartilage breakdown in these patients. Objective: In this study, we examined the effect of lactoferrin on NF-κB activation, cyclooxygenase-2 (COX-2) expression and prostaglandin E2 (PGE2) production in stimulated human articular chondrocytes. Materials and Methods: Human chondrocytes were derived from OA articular cartilage and treated with camel lactoferrin and then stimulated with IL-1β. Gene expression was determined by TaqMan assays and protein expression was studied by Western immunoblotting. NF-κB activity and PGE2 levels were determined by ELISA based assays. NF-κB activity was also determined by treatment of chondrocytes with NF-κB specific inhibitor Bay 11–7082. Results: Lactoferrin inhibited IL-1β-induced activation and nuclear translocation of NF-κB p65 in human OA chondrocytes. Lactoferrin also inhibited mRNA/protein expression of COX-2 and production of PGE2. Moreover, Bay 11–7082 also inhibited IL-1β-induced expression of COX-2 and production of PGE2. The inhibitory effect of lactoferrin on the IL-1β induced expression of COX-2 or production of PGE2 was mediated at least in part via suppression of NF-κB activation. Conclusions: Our data determine camel lactoferrin as a novel inhibitor of IL-1β-induced activation of NF-κB signaling events and production of cartilage-degrading molecule PGE2 via inhibition of COX-2 expressions. These results may have important implications for the development of novel therapeutic strategies for the prevention/treatment of OA and other degenerative/inflammatory diseases. SUMMARY Lactoferrin shows anti-arthritic activity in IL-1β stimulated primary human chondrocytes.Lactoferrin inhibits IL-1β-induced NF-κB activation.Lactoferrin inhibits production of cartilage degrading PGE2 via inhibition of COX-2 expression. Abbreviations Used: OA: Osteoarthritis IL-1β: Interleukin-1 beta NF-κB: Nuclear factor-kappa B COX-2: cyclooxygenase-2 PGE2: prostaglandin E2 PMID:27034605

A novel method for assessing effects of hydrostatic fluid pressure on intracellular calcium: a study with bovine articular chondrocytes.

PubMed

Mizuno, Shuichi

2005-02-01

Chondrocytes in articular cartilage are exposed to hydrostatic pressure and distortional stress during weight bearing and joint loading. Because these stresses occur simultaneously in articular cartilage, the mechanism of mechanosignal transduction due to hydrostatic pressure alone in chondrocytes is not clear. In this study, we attempted to characterize the change in intracellular calcium concentration ([Ca2+]i) in response to the application of hydrostatic fluid pressure (HFP) to cultured bovine articular chondrocytes isolated from defined surface (SZ) and middle zones (MZ) by using a fluorescent indicator (X-rhod-1 AM), a novel custom-made pressure-proof optical chamber, and laser confocal microscopy. Critical methodology implemented in this experiment involved application of high levels of HFP to the cells and the use of a novel imaging apparatus to measure the peak [Ca2+]i in individual cells. The peak [Ca2+]i in MZ cells cultured for 5 days showed a significant twofold increase after the application of HFP at constant 0.5 MPa for 5 min. The peak [Ca2+]i in SZ cells was lower (43%) than that of MZ cells. The peak was suppressed with an inhibitor of dantrolene, gadolinium, or a calcium ion-free buffer, but not with verapamil. This study indicated that the increase in [Ca2+]i in chondrocytes to HFP is dependent on the zonal origin. HFP stimulates calcium mobilization and stretch-activated channels.

An Accurate Full-flexion Anterolateral Portal for Needle Placement in the Knee Joint With Dry Osteoarthritis.

PubMed

Hussein, Mohamed

2017-07-01

Accurate delivery of an injection into the intra-articular space of the knee is achieved in only two thirds of knees when using the standard anterolateral portal. The use of a modified full-flexion anterolateral portal provides a highly accurate, less painful, and more effective method for reproducible intra-articular injection without the need for ultrasonographic or fluoroscopic guidance in patients with dry osteoarthritis of the knee. The accuracy of needle placement was assessed in a prospective series of 140 consecutive injections in patients with symptomatic degenerative knee arthritis without clinical knee effusion. Procedural pain was determined using the Numerical Rating Scale. The accuracy rates of needle placement were confirmed with fluoroscopic imaging to document the dispersion pattern of injected contrast material. Using the standard anterolateral portal, 52 of 70 injections were confirmed to have been placed in the intra-articular space on the first attempt (accuracy rate, 74.2%). Using the modified full-flexion anterolateral portal, 68 of 70 injections were placed in the intra-articular space on the first attempt (accuracy rate, 97.1%; P = 0.000). This study revealed that using the modified full-flexion anterolateral portal for injections into the knee joint resulted in more accurate and less painful injections than those performed by the same orthopaedic surgeon using the standard anterolateral portal. In addition, the technique offered therapeutic delivery into the joint without the need for fluoroscopic confirmation. Therapeutic Level II.

Outcome Determining Factors for displaced Intra-articular Calcaneal Fractures treated operatively

PubMed Central

Chan, KL; Idham, HM; Izani, IM; Nahulan, T

2015-01-01

Introduction: Calcaneal fractures are caused by high energy trauma and mostly are intra-articular fractures. Nondisplaced intra-articular calcaneal fracture (IACF) can be treated non-operatively. However, displaced intra-articular need to be reduced and fixed anatomically to facilitate early ankle rehabilitation and minimize functional impairment. This study was done to find out the outcome of the IACF patients who underwent operative treatment. Methods: 62 patients with IACF were selected in this study and had been followed up from June 2009 to May 2013. They were placed into two groups; the operative treated and non-operative treated groups. Bilateral ankle lateral view plain radiographs were taken for comparison of the Bohler and Gissane angles. Both groups of patients were assessed by the Maryland Foot Score (MFS) and the SF-36v2 general health survey questionnaire. The ability of the patients to perform activity of daily living (ADL) and /or return to work (RTW) was assessed as well. Results: The operative treatment group of displaced IACF patients achieved no significant better scores in the mean MFS and SF-36v2 mean scores as compared to non operated cases. There was no difference in RTW between the 2 groups, but earlier ADL was recorded in the operated group. However, this study had found 5 associated factors which causes major effect to the patients’ outcome to treatment. Conclusions: The patient’s compliance with post-operative rehabilitation regimen were found to be significantly related with the outcomes. PMID:28611903

Paradoxical articular manifestations in patients with inflammatory bowel diseases treated with infliximab.

PubMed

Thiebault, Henri; Boyard-Lasselin, Pauline; Guignant, Caroline; Guillaume, Nicolas; Wacrenier, Adrien; Sabbagh, Charles; Rebibo, Lionel; Brazier, Franck; Meynier, Jonathan; Nguyen-Khac, Eric; Dupas, Jean-Louis; Goëb, Vincent; Fumery, Mathurin

2016-08-01

Articular involvement is the most common extraintestinal manifestation associated with inflammatory bowel diseases (IBDs). Manifestations are 'paradoxical' when they occur during treatment, notably with anti-tumor necrosis factor (anti-TNF) drugs, which are expected to prevent or treat them. The aim of this study was to assess the frequency, characteristics, and associated factors of paradoxical articular manifestations in patients with IBD treated with anti-TNF. In this prospective single-center study, an examination by a rheumatologist was systematically offered to all patients with IBD treated with infliximab (IFX) to assess the prevalence of articular manifestations and distinguish between those related to treatment and those associated with intestinal disease. Paradoxical manifestations were defined as the occurrence of articular manifestations (excluding induced lupus and hypersensitivity reactions) during anti-TNF therapy in patients with intestinal remission. Measures of biological inflammatory, immunological markers, HLA-B27 allele, IFX trough levels, and anti-IFX antibody (Ab) were performed for all patients. Between May 2013 and April 2014, 65 patients with Crohn's disease and 15 with patients ulcerative colitis treated with IFX were included. The median duration of anti-TNF therapy was 66 months [quartile (Q)1=23 months-Q3=81 months]. Articular manifestations were observed in 50 (62%) patients treated with IFX. Eleven percent (n=9) were considered to be associated with IBD and 16% (n=13) to be associated with anti-TNF therapy. Among articular manifestations associated with anti-TNF therapy, nine (11%) patients were considered paradoxical, two (2%) as drug-induced lupus, and two (2%) as a hypersensitivity reaction. Among the nine patients with paradoxical manifestations, all had Crohn's disease in clinical remission, three patients presented a spondyloarthropathy, and three developed associated paradoxical psoriasis. No patient discontinued anti-TNF because of the articular manifestations. Methotrexate was effective on articular symptoms in two of the three treated patients with paradoxical manifestations. No clinical or biological factors, including IFX trough levels, were associated with the occurrence of paradoxical manifestations. Paradoxical articular manifestations in IBD patients treated by anti-TNF are common, affecting more than 10% of patients. These events are generally mild and do not need discontinuation of anti-TNF therapy.

Corrective osteotomy for combined intra- and extra-articular distal radius malunion.

PubMed

Buijze, Geert A; Prommersberger, Karl-Josef; González Del Pino, Juan; Fernandez, Diego L; Jupiter, Jesse B

2012-10-01

This study evaluated the functional outcome of corrective osteotomy for combined intra- and extra-articular malunions of the distal radius using multiple outcome scores. We evaluated 18 skeletally mature patients at an average of 78 months after corrective osteotomy for a combined intra- and extra-articular malunion of the distal part of the radius. The indication for osteotomy in all patients was the combination of an extra-articular deformity (≥ 15° volar or ≥ 10° dorsal angulation or ≥ 3 mm radial shortening) and intra-articular incongruity of 2 mm or greater (maximum stepoff or gap), as measured on lateral and posteroanterior radiographs. The average interval from the injury to the osteotomy was 9 months. The average maximum stepoff or gap of the articular surface before surgery was 4 mm. All 18 patients healed uneventfully and the final articular incongruity was reduced to 2 mm or less. Final range of motion and grip strength significantly improved, averaging 89% and 84% of the uninjured side and 185% and 241% of the preoperative measures, respectively. The rate of excellent or good results was 72% according to the validated rating system Mayo Modified Wrist Score, and 89% according to the unvalidated system of Gartland and Werley. The mean Disabilities of the Arm, Shoulder, and Hand score was 11, which corresponds to mild perceived disability. Of the 18 cases, 11 normalized upper limb function. Five patients had complications; all were successfully treated. According to the rating system of Knirk and Jupiter, 4 had grade 1 and 1 had grade 2 osteoarthritis of the radiocarpal joint on radiographs. Two of those patients reported occasional mild pain. Radiographic osteoarthritis did not correlate with strength, motion, and wrist scores. Outcomes of corrective osteotomy for combined intra- and extra-articular malunions were comparable to those of osteotomy for isolated intra- and extra-articular malunions. A successful corrective osteotomy for the treatment of complex intra- and extra-articular distal radius malunions can improve wrist function. Therapeutic IV. Copyright © 2012 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Articular cartilage regeneration with autologous peripheral blood progenitor cells and hyaluronic acid after arthroscopic subchondral drilling: a report of 5 cases with histology.

PubMed

Saw, Khay-Yong; Anz, Adam; Merican, Shahrin; Tay, Yong-Guan; Ragavanaidu, Kunaseegaran; Jee, Caroline S Y; McGuire, David A

2011-04-01

The purpose of this study was to evaluate the quality of articular cartilage regeneration after arthroscopic subchondral drilling followed by postoperative intraarticular injections of autologous peripheral blood progenitor cells (PBPCs) in combination with hyaluronic acid (HA). Five patients underwent second-look arthroscopy with chondral core biopsy. These 5 patients are part of a larger pilot study in which 180 patients with International Cartilage Repair Society grade III and IV lesions of the knee joint underwent arthroscopic subchondral drilling followed by postoperative intra-articular injections. Continuous passive motion was used on the operated knee 2 hours per day for 4 weeks. Partial weight bearing was observed for the first 6 to 8 weeks. Autologous PBPCs were harvested 1 week after surgery. One week after surgery, 8 mL of the harvested PBPCs in combination with 2 mL of HA was injected intra-articularly into the operated knee. The remaining PBPCs were divided into vials and cryopreserved. A total of 5 weekly intra-articular injections were given. Second-look arthroscopy confirmed articular cartilage regeneration, and histologic sections showed features of hyaline cartilage. Apart from the minimal discomfort of PBPC harvesting and localized pain associated with the intra-articular injections, there were no other notable adverse reactions. Articular hyaline cartilage regeneration is possible with arthroscopic subchondral drilling followed by postoperative intraarticular injections of autologous PBPCs in combination with HA. Level IV, therapeutic case series. Copyright © 2011 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Quantitative characterization of mesenchymal stem cell adhesion to the articular cartilage surface.

PubMed

Hung, Ben P; Babalola, Omotunde M; Bonassar, Lawrence J

2013-12-01

There has been great interest in use of mesenchymal stem cell (MSC)-based therapies for cartilage repair. Most recently, treatments involving intra-articular injection of MSCs have shown great promise for cartilage repair and arthritis therapy, which rely on MSC adhesion to cartilage. While there is some information on chondrocyte adhesion to cartilage, there is relatively little known about the kinetics and strength of MSC adhesion to cartilage. The goals of this study were as follows: (1) to quantify the kinetics and strength of adhesion of marrow-derived MSCs to articular cartilage using standard laboratory hardware; (2) to compare this adhesion behavior to that of articular chondrocytes; and (3) to assess the effect of serial monolayer culture on MSC adhesion. First through fourth passage MSCs and primary articular chondrocytes were allowed to adhere to the articular surface of cartilage disks for up to 30 h and the number of adhered cells was recorded to quantify adhesion kinetics. After 30 h, adherent cells were subjected to centrifugal shear to determine adhesion strength, quantified as the shear necessary to detach half the adhered cells (σ50 ). The number of adhered MSCs and adhesion strength increased with passage number and MSCs adhered more strongly than did primary articular chondrocytes. As such, the kinetics and strength of MSC adhesion to cartilage is not dramatically lower than that for articular chondrocytes. This protocol for assessing cell adhesion to cartilage is simple to implement and may represent an important screening tool for assessing the efficacy of cell-based therapies for cartilage repair. Copyright © 2013 Wiley Periodicals, Inc., a Wiley Company.

Polyglycolic acid-hyaluronan scaffolds loaded with bone marrow-derived mesenchymal stem cells show chondrogenic differentiation in vitro and cartilage repair in the rabbit model.

PubMed

Patrascu, Jenel M; Krüger, Jan Philipp; Böss, Hademar G; Ketzmar, Anna-Katharina; Freymann, Undine; Sittinger, Michael; Notter, Michael; Endres, Michaela; Kaps, Christian

2013-10-01

In cartilage repair, scaffold-assisted one-step approaches are used to improve the microfracture (Mfx) technique. Since the number of progenitors in Mfx is low and may further decrease with age, aim of our study was to analyze the chondrogenic potential of freeze-dried polyglycolic acid-hyaluronan (PGA-HA) implants preloaded with mesenchymal stem cells (MSCs) in vitro and in a rabbit articular cartilage defect model. Human bone marrow-derived MSC from iliac crest were cultured in freeze-dried PGA-HA implants for chondrogenic differentiation. In a pilot study, implants were loaded with autologous rabbit MSC and used to cover 5 mm × 6 mm full-thickness femoral articular cartilage defects (n = 4). Untreated defects (n = 3) served as controls. Gene expression analysis and histology showed induction of typical chondrogenic marker genes like type II collagen and formation of hyaline-like cartilaginous tissue in MSC-laden PGA-HA implants. Histological evaluation of rabbit repair tissue formation after 30 and 45 days showed formation of repair tissue, rich in chondrocytic cells and of a hyaline-like appearance. Controls showed no articular resurfacing, tissue repair in the subchondral zone and fibrin formation. These results suggest that MSC-laden PGA-HA scaffolds have chondrogenic potential and are a promising option for stem cell-mediated cartilage regeneration. Copyright © 2013 Wiley Periodicals, Inc.

Multi-pelvis characterisation of articular cartilage geometry.

PubMed

Gillard, Faye C; Dickinson, Alexander S; Schneider, Urs; Taylor, Andrew C; Browne, Martin

2013-12-01

The shape of the acetabular cartilage follows the contact stress distribution across the joint. Accurate characterisation of this geometry may be useful for the development of acetabular cup devices that are more biomechanically compliant. In this study, the geometry of the acetabular cartilage was characterised by taking plaster moulds of the acetabulum from 24 dry bone human pelvises and digitising the mould shapes using a three-dimensional laser scanner. The articular bone surface geometry was analysed, and the shape of the acetabulum was approximated by fitting a best-fit sphere. To test the hypothesis that the acetabulum is non-spherical, a best-fit ellipsoid was also fitted to the geometry. In each case, points around the acetabular notch edge that disclosed the articular surface geometry were identified, and vectors were drawn between these and the best-fit sphere or ellipsoid centre. The significantly larger z radii (into the pole) of the ellipsoids indicated that the acetabulum was non-spherical and could imply that the kinematics of the hip joint is more complex than purely rotational motion, and the traditional ball-and-socket replacement may need to be updated to reflect this motion. The acetabular notch edges were observed to be curved, with males exhibiting deeper, wider and shorter notches than females, although the difference was not statistically significant (mean: p = 0.30) and supports the use of non-gender-specific models in anatomical studies.

A sound and efficient measure of joint congruence.

PubMed

Conconi, Michele; Castelli, Vincenzo Parenti

2014-09-01

In the medical world, the term "congruence" is used to describe by visual inspection how the articular surfaces mate each other, evaluating the joint capability to distribute an applied load from a purely geometrical perspective. Congruence is commonly employed for assessing articular physiology and for the comparison between normal and pathological states. A measure of it would thus represent a valuable clinical tool. Several approaches for the quantification of joint congruence have been proposed in the biomechanical literature, differing on how the articular contact is modeled. This makes it difficult to compare different measures. In particular, in previous articles a congruence measure has been presented which proved to be efficient and suitable for the clinical practice, but it was still empirically defined. This article aims at providing a sound theoretical support to this congruence measure by means of the Winkler elastic foundation contact model which, with respect to others, has the advantage to hold also for highly conforming surfaces as most of the human articulations are. First, the geometrical relation between the applied load and the resulting peak of pressure is analytically derived from the elastic foundation contact model, providing a theoretically sound approach to the definition of a congruence measure. Then, the capability of congruence measure to capture the same geometrical relation is shown. Finally, the reliability of congruence measure is discussed. © IMechE 2014.

Micrometer scale guidance of mesenchymal stem cells to form structurally oriented large-scale tissue engineered cartilage.

PubMed

Chou, Chih-Ling; Rivera, Alexander L; Williams, Valencia; Welter, Jean F; Mansour, Joseph M; Drazba, Judith A; Sakai, Takao; Baskaran, Harihara

2017-09-15

Current clinical methods to treat articular cartilage lesions provide temporary relief of the symptoms but fail to permanently restore the damaged tissue. Tissue engineering, using mesenchymal stem cells (MSCs) combined with scaffolds and bioactive factors, is viewed as a promising method for repairing cartilage injuries. However, current tissue engineered constructs display inferior mechanical properties compared to native articular cartilage, which could be attributed to the lack of structural organization of the extracellular matrix (ECM) of these engineered constructs in comparison to the highly oriented structure of articular cartilage ECM. We previously showed that we can guide MSCs undergoing chondrogenesis to align using microscale guidance channels on the surface of a two-dimensional (2-D) collagen scaffold, which resulted in the deposition of aligned ECM within the channels and enhanced mechanical properties of the constructs. In this study, we developed a technique to roll 2-D collagen scaffolds containing MSCs within guidance channels in order to produce a large-scale, three-dimensional (3-D) tissue engineered cartilage constructs with enhanced mechanical properties compared to current constructs. After rolling the MSC-scaffold constructs into a 3-D cylindrical structure, the constructs were cultured for 21days under chondrogenic culture conditions. The microstructure architecture and mechanical properties of the constructs were evaluated using imaging and compressive testing. Histology and immunohistochemistry of the constructs showed extensive glycosaminoglycan (GAG) and collagen type II deposition. Second harmonic generation imaging and Picrosirius red staining indicated alignment of neo-collagen fibers within the guidance channels of the constructs. Mechanical testing indicated that constructs containing the guidance channels displayed enhanced compressive properties compared to control constructs without these channels. In conclusion, using a novel roll-up method, we have developed large scale MSC based tissue-engineered cartilage that shows microscale structural organization and enhanced compressive properties compared to current tissue engineered constructs. Tissue engineered cartilage constructs made with human mesenchymal stem cells (hMSCs), scaffolds and bioactive factors are a promising solution to treat cartilage defects. A major disadvantage of these constructs is their inferior mechanical properties compared to the native tissue, which is likely due to the lack of structural organization of the extracellular matrix of the engineered constructs. In this study, we developed three-dimensional (3-D) cartilage constructs from rectangular scaffold sheets containing hMSCs in micro-guidance channels and characterized their mechanical properties and metabolic requirements. The work led to a novel roll-up method to embed 2-D microscale structures in 3-D constructs. Further, micro-guidance channels incorporated within the 3-D cartilage constructs led to the production of aligned cell-produced matrix and enhanced mechanical function. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

The effect of variable size posterior wall acetabular fractures on contact characteristics of the hip joint.

PubMed

Olson, S A; Bay, B K; Pollak, A N; Sharkey, N A; Lee, T

1996-01-01

The indications for open reduction and internal fixation of posterior wall acetabular fractures associated with a clinically stable hip joint are unclear. In previous work a large posterior wall defect (27% articular surface area) resulted in significant alteration of load transmission across the hip; specifically, there was a transition from evenly distributed loading along the acetabular articular surface to loading concentrated mainly in the superior portion of the articular surface during simulated single leg stance. However, the majority of posterior wall fractures involve a smaller amount of the articular surface. Posterior wall acetabular fractures not associated with instability of the hip are commonly treated nonoperatively. This practice does not account for the size of the posterior wall fracture. To study the biomechanical consequences of variably sized articular defects, a laboratory experiment was conducted evaluating three progressively larger posterior wall defects of the acetabulum during simulated single leg stance using superlow Fuji prescale film (Itochu International, New York): (a) 1/3 articular surface width through a 50 degrees arc along the posterior wall of the acetabulum, (b) 2/3, and (c) 3/3 articular width defects through the same 50 degrees arc along the posterior wall of the acetabulum. In the intact acetabulum, 48% of the total articular contact was located in the superior acetabulum. Twenty-eight percent of articular contact was in the anterior wall region of the acetabulum and 24% in the posterior wall region. After the 1/3 width posterior wall defect, 64% of the articular contact was located in the superior acetabulum (p = 0.0011). The 2/3 width posterior wall defect resulted in 71% of articular contact area being located in the superior acetabulum (p = 0.0006). After the 3/3 width posterior wall defect, 77% of articular contact was located in the superior acetabulum, significantly greater than the intact condition (p < 0.0001) and 1/3 width defect (p = 0.0222). The total absolute contact areas for all defect conditions were significantly less than the intact conditions. The results of this study reconfirm the observation that posterior wall fractures of the acetabulum significantly alter the articular contact characteristics in the hip during single leg stance. The relationship between defect size and changes in joint contact showed that the smallest defect resulted in the greatest alteration in joint contact areas, whereas larger defects resulted in minor increments of change in contact area. This finding is of concern because the clinical practice of managing acetabular fractures nonoperatively if the hip joint is stable is based on the supposition that the joint retains enough integrity to function without undue risk of late posttraumatic osteoarthritis. A better understanding of the natural history of stable posterior wall acetabular fractures is needed to ascertain whether some of these fractures merit operative repair.

Targeting TGFβ Signaling in Subchondral Bone and Articular Cartilage Homeostasis

PubMed Central

Zhen, Gehau; Cao, Xu

2014-01-01

Osteoarthritis (OA) is the most common degenerative joint disease, and there is no disease-modifying therapy for OA currently available. Targeting of articular cartilage alone may not be sufficient to halt this disease progression. Articular cartilage and subchondral bone act as a functional unit. Increasing evidence indicates that transforming growth factor β (TGFβ) plays a crucial role in maintaining homeostasis of both articular cartilage and subchondral bone. Activation of extracellular matrix latent TGFβ at the appropriate time and location is the prerequisite for its function. Aberrant activation of TGFβ in the subchondral bone in response to abnormal mechanical loading environment induces formation of osteroid islets at onset of osteoarthritis. As a result, alteration of subchondral bone structure changes the stress distribution on the articular cartilage and leads to its degeneration. Thus, inhibition of TGFβ activity in the subchondral bone may provide a new avenue of treatment for OA. In this review, we will respectively discuss the role of TGFβ in homeostasis of articular cartilage and subchondral bone as a novel target for OA therapy. PMID:24745631

Severe extra-articular manifestations of rheumatoid arthritis in absence of concomitant joint involvement following long-term spontaneous remission. A case report.

PubMed

Lagrutta, Mariana; Alle, Gelsomina; Parodi, Roberto Leandro; Greca, Alcides Alejandro

2016-01-01

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease occasionally associated with severe extra-articular manifestations, mostly in cases of longstanding highly active disease. We report the case of a 56 year-old woman diagnosed with active RA at the age of 40. After 5 years of high activity, her arthritis subsides spontaneously during pregnancy despite the lack of treatment with disease-modifying anti-rheumatic drugs. She remains without articular symptoms for 7 years, and then she develops a Felty's syndrome requiring steroid treatment and splenectomy. Following steroid withdrawal she develops pericarditis with massive serohematic pericardial effusion, still in absence of articular activity, and responds to immunosuppressive therapy and colchicine. We emphasize the unusual spontaneous and sustained joint remission without specific treatment, and the development of severe extra-articular manifestations of RA in absence of concomitant articular activity, as well as the importance of controlling inflammation. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Comparison of intra-articular methotrexate with intra-articular triamcinolone hexacetonide by thermography.

PubMed

Bird, H A; Ring, E F; Daniel, R; Bacon, P A

1977-01-01

A comparison of intra-articular methotrexate and intra-articular triamcinolone hexacetonide was made in 42 arthritic patients with persistent bilateral knee effusions. One knee was injected with either 5 mg methotrexate (two injections of 2.5 mg a week apart) or a single injection of 20 mg triamcinolone. An objective assessment of both knees was made by quantitative thermography at 0,3,7,14 and 21 days. Joints injected with triamcinolone showed a greater fall in thermographic index (T.I) than the joints injected with methotrexate, which showed similar change to the non-injected knee joints in both groups. Four patients received larger doses of methotrexate, up to 20 mg, though the fall in T.I. was still less than the mean fall for triamcinolone injected joints. Peak venous blood levels of methotrexate were reached 1 hour after intra-articular injection, and a sphygmomanometer cuff inflated around the leg above the injected knee for periods of up to 1 hour did not appreciably delay this. Methotrexate had no immediate anti-inflammatory effect, even in psoriatic arthropathy, and did not give the relief of intra-articular steroid.

Customized Fabrication of Osteochondral Tissue for Articular Joint Surface Repair

DTIC Science & Technology

2015-09-01

Kilroy EJ, Tuan RS. (2015) Projection Stereolithographic Fabrication of Human Adipose Stem Cell-incorporated Biodegradable Scaffolds for Cartilage...necessary to include the publications already specified above in this section. Nothing to Report (1) Live Cell-scaffold Printing using Biodegradable ...and PCL scaffolds using PSL (Figure 1,2). Solid PDLLA-PEG scaffold (30%) possesses a compressive modulus up to 800kPa and is biodegradable in

Measurements of surface layer of the articular cartilage using microscopic techniques

NASA Astrophysics Data System (ADS)

Ryniewicz, A. M.; Ryniewicz, A.; Ryniewicz, W.; Gaska, A.

2010-07-01

The articular cartilage is the structure that directly cooperates tribologically in biobearing. It belongs to the connective tissues and in the joints it assumes two basic forms: hyaline cartilage that builds joint surfaces and fibrocartilage which may create joint surfaces. From this fibrocartilage are built semilunar cartilage and joint disc are built as well. The research of articular cartilage have been done in macro, micro and nano scale. In all these measurement areas characteristic features occur which can identify biobearing tribology. The aim of the research was the identification of surface layer of articular cartilage by means of scanning electron microscopy (SEM) and atom force microscopy (AFM) and the analysis of topography of these layers. The material used in the research of surface layer was the animal articular cartilage: hyaline cartilage and fibrocartilage.

Halofuginone attenuates articular cartilage degeneration by inhibition of elevated TGF‑β1 signaling in articular cartilage in a rodent osteoarthritis model.

PubMed

Mu, Wenbo; Xu, Boyong; Ma, Hairong; Ji, Baochao; Zhang, Zhendong; Li, Jiao; Amat, Abdusami; Cao, Li

2017-11-01

Osteoarthritis (OA) is the most common degenerative condition of the weight‑bearing joints worldwide without effective medical therapy. In order to investigate whether administration of halofuginone (HF) may attenuate OA, the present study allocated 3‑month‑old male mice into Sham group, vehicle‑treated anterior cruciate ligament transection (ACLT) group and HF‑treated ACLT group. The present study determined that HF treatment reduced the expression of matrix metallopeptidase‑13 and collagen X in articular cartilage. Additionally, it lowered the Osteoarthritis Research Society International‑Modified Mankin score and prevented the loss of articular cartilage from Safranin O and Fast Green staining. HF reduced the progression of osteoarthritis by downregulating abnormally elevated TGF‑β1 activity in articular cartilage. Administration of HF may be a potential preventive therapy for OA.

Current Concepts in Treatment of Patellofemoral Osteochondritis Dissecans

PubMed Central

Paine, Russ; Chicas, Eric; Gardner, Emily; Bailey, Lane; McDermott, James

2016-01-01

Identification, protection, and management of patellofemoral articular cartilage lesions continue to remain on the forefront of sports medicine rehabilitation. Due to high-level compression forces that are applied through the patellofemoral (PF) joint, managing articular cartilage lesions is challenging for sports medicine specialists. Articular cartilage damage may exist in a wide spectrum of injuries ranging from small, single areas of focal damage to wide spread osteoarthritis involving large chondral regions. Management of these conditions has evolved over the last two centuries, most recently using biogenetic materials and cartilage replacement modalities. The purpose of this clinical commentary is to discuss PF articular cartilage injuries, etiological variables, and investigate the evolution in management of articular cartilage lesions. Rehabilitation of these lesions will also be discussed with a focus on current trends and return to function criteria. Level of Evidence 5 PMID:27904793

Mathematics as a conduit for translational research in post-traumatic osteoarthritis.

PubMed

Ayati, Bruce P; Kapitanov, Georgi I; Coleman, Mitchell C; Anderson, Donald D; Martin, James A

2017-03-01

Biomathematical models offer a powerful method of clarifying complex temporal interactions and the relationships among multiple variables in a system. We present a coupled in silico biomathematical model of articular cartilage degeneration in response to impact and/or aberrant loading such as would be associated with injury to an articular joint. The model incorporates fundamental biological and mechanical information obtained from explant and small animal studies to predict post-traumatic osteoarthritis (PTOA) progression, with an eye toward eventual application in human patients. In this sense, we refer to the mathematics as a "conduit of translation." The new in silico framework presented in this paper involves a biomathematical model for the cellular and biochemical response to strains computed using finite element analysis. The model predicts qualitative responses presently, utilizing system parameter values largely taken from the literature. To contribute to accurate predictions, models need to be accurately parameterized with values that are based on solid science. We discuss a parameter identification protocol that will enable us to make increasingly accurate predictions of PTOA progression using additional data from smaller scale explant and small animal assays as they become available. By distilling the data from the explant and animal assays into parameters for biomathematical models, mathematics can translate experimental data to clinically relevant knowledge. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:566-572, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Biomechanical Evaluation of Standard Versus Extended Proximal Fixation Olecranon Plates for Fixation of Olecranon Fractures.

PubMed

Boden, Allison L; Daly, Charles A; Dalwadi, Poonam P; Boden, Stephanie A; Hutton, William C; Muppavarapu, Raghuveer C; Gottschalk, Michael B

2018-01-01

Small olecranon fractures present a significant challenge for fixation, which has resulted in development of plates with proximal extension. Olecranon-specific plates with proximal extensions are widely thought to offer superior fixation of small proximal fragments but have distinct disadvantages: larger dissection, increased hardware prominence, and the increased possibility of impingement. Previous biomechanical studies of olecranon fracture fixation have compared methods of fracture fixation, but to date there have been no studies defining olecranon plate fixation strength for standard versus extended olecranon plates. The purpose of this study is to evaluate the biomechanical utility of the extended plate for treatment of olecranon fractures. Sixteen matched pairs of fresh-frozen human cadaveric elbows were used. Of the 16, 8 matched pairs received a transverse osteotomy including 25% and 8 including 50% of the articular surface on the proximal fragment. One elbow from each pair was randomly assigned to a standard-length plate, and the other elbow in the pair received the extended-length plate, for fixation of the fracture. The ulnae were cyclically loaded and subsequently loaded to failure, with ultimate load, number of cycles, and gap formation recorded. There was no statistically significant difference between the standard and extended fixation plates in simple transverse fractures at either 25% or 50% from the proximal most portion of the articular surface of the olecranon. Standard fixation plates are sufficient for the fixation of small transverse fractures, but caution should be utilized particularly with comminution and nontransverse fracture patterns.

Periocular and Intra-Articular Injection of Canine Adipose-Derived Mesenchymal Stem Cells: An In Vivo Imaging and Migration Study

PubMed Central

Wood, Joshua A.; Chung, Dai-Jung; Park, Shin Ae; Zwingenberger, Allison L.; Reilly, Christopher M.; Ly, Irene; Walker, Naomi J.; Vernau, William; Hayashi, Kei; Wisner, Erik R.; Cannon, Matthew S.; Kass, Philip H.; Cherry, Simon R.; Borjesson, Dori L.; Russell, Paul

2012-01-01

Abstract Purpose Immune-mediated diseases affect millions of people worldwide with an economic impact measured in the billions of dollars. Mesenchymal stem cells (MSCs) are being investigated in the treatment of certain immune mediated diseases, but their application in the treatment of the majority of these disorders remains largely unexplored. Keratoconjunctivitis sicca can occur as a result of progressive immune-mediated destruction of lacrimal tissue in dogs and humans, and immune-mediated joint disease is common to both species. In dogs, allogeneic MSC engraftment and migration have yet to be investigated in vivo in the context of repeated injections. Methods With these aims in mind, the engraftment of allogeneic canine MSCs after an injection into the periocular and intra-articular regions was followed in vivo using magnetic resonance and fluorescent imaging. Results The cells were shown to be resident near the site of the injection for a minimum of 2 weeks. Analysis of 61 tissues demonstrated preferential migration and subsequent engraftment of MSCs in the thymus as well as the gastrointestinal tract. These results also detail a novel in vivo imaging technique and demonstrate the differential spatial distribution of MSCs after migration away from the sites of local delivery. Conclusion The active engraftment of the MSCs in combination with their previously documented immunomodulatory capabilities suggests the potential for therapeutic benefit in using MSCs for the treatment of periocular and joint diseases with immune involvement. PMID:22175793

Repair of articular osteochondral defects of the knee joint using a composite lamellar scaffold.

PubMed

Lv, Y M; Yu, Q S

2015-04-01

The major problem with repair of an articular cartilage injury is the extensive difference in the structure and function of regenerated, compared with normal cartilage. Our work investigates the feasibility of repairing articular osteochondral defects in the canine knee joint using a composite lamellar scaffold of nano-ß-tricalcium phosphate (ß-TCP)/collagen (col) I and II with bone marrow stromal stem cells (BMSCs) and assesses its biological compatibility. The bone-cartilage scaffold was prepared as a laminated composite, using hydroxyapatite nanoparticles (nano-HAP)/collagen I/copolymer of polylactic acid-hydroxyacetic acid as the bony scaffold, and sodium hyaluronate/poly(lactic-co-glycolic acid) as the cartilaginous scaffold. Ten-to 12-month-old hybrid canines were randomly divided into an experimental group and a control group. BMSCs were obtained from the iliac crest of each animal, and only those of the third generation were used in experiments. An articular osteochondral defect was created in the right knee of dogs in both groups. Those in the experimental group were treated by implanting the composites consisting of the lamellar scaffold of ß-TCP/col I/col II/BMSCs. Those in the control group were left untreated. After 12 weeks of implantation, defects in the experimental group were filled with white semi-translucent tissue, protruding slightly over the peripheral cartilage surface. After 24 weeks, the defect space in the experimental group was filled with new cartilage tissues, finely integrated into surrounding normal cartilage. The lamellar scaffold of ß-TCP/col I/col II was gradually degraded and absorbed, while new cartilage tissue formed. In the control group, the defects were not repaired. This method can be used as a suitable scaffold material for the tissue-engineered repair of articular cartilage defects. Cite this article: Bone Joint Res 2015;4:56-64. ©2015 The British Editorial Society of Bone & Joint Surgery.

Hyaluronan Protects Bovine Articular Chondrocytes against Cell Death Induced by Bupivacaine under Supraphysiologic Temperatures

PubMed Central

Liu, Sen; Zhang, Qing-Song; Hester, William; O’Brien, Michael J.; Savoie, Felix H.; You, Zongbing

2013-01-01

Background Bupivacaine and supraphysiologic temperature can independently reduce cell viability of articular chondrocytes. In combination these two deleterious factors could further impair cell viability. Hypothesis Hyaluronan may protect chondrocytes from death induced by bupivacaine at supraphysiologic temperatures. Study Design Controlled laboratory study. Methods Bovine articular chondrocytes were treated with hyaluronan at physiologic (37°C) and supraphysiologic temperatures (45°C and 50°C) for one hour, and then exposed to bupivacaine for one hour at room temperature. Cell viability was assessed at three time points: immediately after treatment, six hours later, and twenty-four hours later using flow cytometry and fluorescence microscopy. The effects of hyaluronan on the levels of sulfated glycosaminoglycan in the chondrocytes were determined using Alcian blue staining. Results (1) Bupivacaine alone did not induce noticeable chondrocyte death at 37°C; (2) bupivacaine and temperature synergistically increased chondrocyte death, that is, when the chondrocytes were conditioned to 45°C and 50°C, 0.25% and 0.5% bupivacaine increased the cell death rate by 131% to 383% in comparison to the phosphate-buffered saline control group; and, (3) addition of hyaluronan reduced chondrocyte death rates to approximately 14% and 25% at 45°C and 50°C, respectively. Hyaluronan’s protective effects were still observed at six and twenty-four hours after bupivacaine treatment at 45°C. However, at 50°C, hyaluronan delayed but did not prevent the cell death caused by bupivacaine. One-hour treatment with hyaluronan significantly increased sulfated glycosaminoglycan levels in the chondrocytes. Conclusions Bupivacaine and supraphysiologic temperature synergistically increase chondrocyte death and hyaluronan may protect articular chondrocytes from death caused by bupivacaine. Clinical Relevance This study provides a rationale to perform pre-clinical and clinical studies to evaluate whether intra-articular injection of a mixture of bupivacaine and hyaluronan after arthroscopic surgery may protect against bupivacaine’s chondrotoxicity. PMID:22427617

A Single-Dose Intra-Articular Morphine plus Bupivacaine versus Morphine Alone following Knee Arthroscopy: A Systematic Review and Meta-Analysis

PubMed Central

Wang, Yi-lun; Li, Yu-sheng; Wei, Jie; Li, Hui; Yang, Tuo; Yang, Tu-bao; Lei, Guang-hua

2015-01-01

Objectives The purpose of this study was to compare the efficacy and safety of a single-dose intra-articular morphine plus bupivacaine versus morphine alone in patients undergoing arthroscopic knee surgery. Methods Randomized controlled trials comparing a combination of morphine and bupivacaine with morphine alone injected intra-articularly in the management of pain after knee arthrocopic surgery were retrieved (up to August 10, 2014) from MEDLINE, the Cochrane Library and Embase databases. The weighted mean difference (WMD), relative risk (RR) and their corresponding 95% confidence intervals (CIs) were calculated using RevMan statistical software. Results Thirteen randomized controlled trials were included. Statistically significant differences were observed with regard to the VAS values during the immediate period (0-2h) (WMD -1.16; 95% CI -2.01 to -0.31; p = 0.007) and the time to first request for rescue analgesia (WMD = 2.05; 95% CI 0.19 to 3.92; p = 0.03). However, there was no significant difference in the VAS pain score during the early period (2-6h) (WMD -0.36; 95% CI -1.13 to 0.41; p = 0.35), the late period (6-48h) (WMD 0.11; 95% CI -0.40 to 0.63; p = 0.67), and the number of patients requiring supplementary analgesia (RR = 0.78; 95% CI 0.57 to 1.05; p = 0.10). In addition, systematic review showed that intra-articular morphine plus bupivacaine would not increase the incidence of adverse effects compared with morphine alone. Conclusion The present study suggested that the administration of single-dose intra-articular morphine plus bupivacaine provided better pain relief during the immediate period (0-2h), and lengthened the time interval before the first request for analgesic rescue without increasing the short-term side effects when compared with morphine alone. Level of Evidence Level I, meta-analysis of Level I studies. PMID:26474401

The Analgesic Effects of Morphine and Tramadol Added to Intra-articular Levobupivacaine-Tenoxicam Combination for Arthroscopic Knee Surgery on Postoperative Pain; a Randomized Clinical Trial

PubMed Central

Oral, Ebru Gelici; Hanci, Ayse; Ulufer Sivrikaya, Gulcihan; Dobrucali, Hale; Turkoglu Kilinc, Leyla

2015-01-01

Background: Arthroscopic knee surgery is commonly performed as an outpatient procedure and is often associated with postoperative pain. Objectives: We aimed to compare the effects of intra-articular levobupivacaine-tenoxicam-tramadol and levobupivacaine-tenoxicam-morphine combinations on postoperative pain in patients undergoing elective arthroscopic knee surgery. Materials and Methods: A total of 90 ASA I-II patients undergoing elective arthroscopic meniscectomy under general anesthesia were enrolled. The participants were randomly allocated to three groups to receive the following intra-articular medications after completion of the surgery and before deflation of the tourniquet: Group S, 20 mL of saline; Group T, 35 mg of levobupivacaine, 20 mg of tenoxicam, and 100 mg of tramadol in 20 mL saline; and Group M, 35 mg of levobupivacaine, 20 mg of tenoxicam, and 4 mg of morphine in 20 mL saline. Visual analogue scale values at rest (VASr) and at active flexion of knee (VASa) at postoperation hours 1, 2, 4, 8, 12, and 24, duration of analgesia, total analgesic consumption, and number of rescue analgesia at 24 hours were evaluated. Results: VASr and VASa were significantly higher in group S in comparison to other groups (P < 0.05). Duration of analgesia was significantly longer in Group T and Group M than in Group S (P < 0.05). The difference between group T and group M was also significant (P < 0.05). Number of rescue analgesia and total analgesic consumption at postoperative hour 24 was significantly fewer in group M compared with other groups (P < 0.05). Conclusions: Intra-articular levobupivacaine-tenoxicam-morphine combination provides effective pain relief, longer analgesic duration, and less analgesic requirement when compared with intra-articular levobupivacaine-tenoxicam-tramadol combination and saline after knee arthroscopic surgery. PMID:26161321

The degeneration and destruction of femoral articular cartilage shows a greater degree of deterioration than that of the tibial and patellar articular cartilage in early stage knee osteoarthritis: a cross-sectional study.

PubMed

Hada, S; Kaneko, H; Sadatsuki, R; Liu, L; Futami, I; Kinoshita, M; Yusup, A; Saita, Y; Takazawa, Y; Ikeda, H; Kaneko, K; Ishijima, M

2014-10-01

The aim of the present study was to examine whether the degenerative and morphological changes of articular cartilage in early stage knee osteoarthritis (OA) occurred equally for both femoral- and tibial- or patellar- articular cartilage using magnetic resonance imaging (MRI)-based analyses. This cross-sectional study was approved by the ethics committee of our university. Fifty patients with early stage painful knee OA were enrolled. The patients underwent 3.0 T MRI on the affected knee joint. Healthy volunteers who did not show MRI-based OA changes were also recruited as controls (n = 19). The degenerative changes of the articular cartilage were quantified by a T2 mapping analysis, and any structural changes were conducted using Whole Organ Magnetic Resonance Imaging Score (WORMS) technique. All patients showed MRI-detected OA morphological changes. The T2 values of femoral condyle (FC) (P < 0.0001) and groove (P = 0.0001) in patients with early stage knee OA were significantly increased in comparison to those in the control, while no significant differences in the T2 values of patellar and tibial plateau (TP) were observed between the patients and the control. The WORMS cartilage and osteophyte scores of the femoral articular cartilage were significantly higher than those in the patellar- (P = 0.001 and P = 0.007, respectively) and tibial- (P = 0.0001 and P < 0.0001, respectively) articular cartilage in the patients with early stage knee OA. The degradation and destruction of the femoral articular cartilage demonstrated a greater degree of deterioration than those of the tibial- and patellar- articular cartilage in patients with early stage knee OA. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Intra-articular corticosteroids versus intra-articular corticosteroids plus methotrexate in oligoarticular juvenile idiopathic arthritis: a multicentre, prospective, randomised, open-label trial.

PubMed

Ravelli, Angelo; Davì, Sergio; Bracciolini, Giulia; Pistorio, Angela; Consolaro, Alessandro; van Dijkhuizen, Evert Hendrik Pieter; Lattanzi, Bianca; Filocamo, Giovanni; Verazza, Sara; Gerloni, Valeria; Gattinara, Maurizio; Pontikaki, Irene; Insalaco, Antonella; De Benedetti, Fabrizio; Civino, Adele; Presta, Giuseppe; Breda, Luciana; Marzetti, Valentina; Pastore, Serena; Magni-Manzoni, Silvia; Maggio, Maria Cristina; Garofalo, Franco; Rigante, Donato; Gattorno, Marco; Malattia, Clara; Picco, Paolo; Viola, Stefania; Lanni, Stefano; Ruperto, Nicolino; Martini, Alberto

2017-03-04

Little evidence-based information is available to guide the treatment of oligoarticular juvenile idiopathic arthritis. We aimed to investigate whether oral methotrexate increases the efficacy of intra-articular corticosteroid therapy. We did this prospective, open-label, randomised trial at ten hospitals in Italy. Using a concealed computer-generated list, children younger than 18 years with oligoarticular-onset disease were randomly assigned (1:1) to intra-articular corticosteroids alone or in combination with oral methotrexate (15 mg/m 2 ; maximum 20 mg). Corticosteroids used were triamcinolone hexacetonide (shoulder, elbow, wrist, knee, and tibiotalar joints) or methylprednisolone acetate (ie, subtalar and tarsal joints). We did not mask patients or investigators to treatment assignments. Our primary outcome was the proportion of patients in the intention-to-treat population who had remission of arthritis in all injected joints at 12 months. This trial is registered with European Union Clinical Trials Register, EudraCT number 2008-006741-70. Between July 7, 2009, and March 31, 2013, we screened 226 participants and randomly assigned 102 to intra-articular corticosteroids alone and 105 to intra-articular corticosteroids plus methotrexate. 33 (32%) patients assigned to intra-articular corticosteroids alone and 39 (37%) assigned to intra-articular corticosteroids and methotrexate therapy had remission of arthritis in all injected joints (p=0·48). Adverse events were recorded for 20 (17%) patients who received methotrexate, which led to permanent treatment discontinuation in two patients (one due to increased liver transaminases and one due to gastrointestinal discomfort). No patient had a serious adverse event. Concomitant administration of methotrexate did not augment the effectiveness of intra-articular corticosteroid therapy. Future studies are needed to define the optimal therapeutic strategies for oligoarticular juvenile idiopathic arthritis. Italian Agency of Drug Evaluation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Displaced intra-articular calcaneal fractures.

PubMed

Bajammal, Sohail; Tornetta, Paul; Sanders, David; Bhandari, Mohit

2005-01-01

Calcaneal fractures comprise 1 to 2 percent of all fractures. Approximately 75% of calcaneal fractures are intra-articular. The management of intra-articular calcaneal fractures remains controversial. Nonoperative treatment options include elevation, ice, early mobilization, and cyclic compression of the plantar arch. Operative treatment options include closed reduction and percutaneous pin fixation, open reduction and internal fixation, and arthrodesis. The effect of operative versus nonoperative treatment has been the focus of several comparative studies. This study was designed to determine the effect of operative treatment compared with nonoperative treatment on the rate of union, complications, and functional outcome after intra-articular calcaneal fracture in adults.

A new building block: costo-osteochondral graft for intra-articular incongruity after distal radius fracture.

PubMed

Tang, Chris Yuk Kwan; Fung, Boris; Poon, T L; Fok, Margaret

2014-01-01

Even with the invention of locking plates, intra-articular fractures of distal radius with extreme comminution remain a challenge for orthopaedic surgeons. Osteochondral graft is a potential choice to reconstruct the articular defect. We report a patient who had a fracture of distal radius with costo-osteochondral graft for articular reconstruction which has not yet been described in the English literature. At nine-year follow-up, he was pain free and had full range of movement of the wrist. The authors suggest that costo-osteochondral graft could be an option with satisfactory result.

Culture Medium Supplements Derived from Human Platelet and Plasma: Cell Commitment and Proliferation Support

PubMed Central

Muraglia, Anita; Nguyen, Van Thi; Nardini, Marta; Mogni, Massimo; Coviello, Domenico; Dozin, Beatrice; Strada, Paolo; Baldelli, Ilaria; Formica, Matteo; Cancedda, Ranieri; Mastrogiacomo, Maddalena

2017-01-01

Present cell culture medium supplements, in most cases based on animal sera, are not fully satisfactory especially for the in vitro expansion of cells intended for human cell therapy. This paper refers to (i) an heparin-free human platelet lysate (PL) devoid of serum or plasma components (v-PL) and (ii) an heparin-free human serum derived from plasma devoid of PL components (Pl-s) and to their use as single components or in combination in primary or cell line cultures. Human mesenchymal stem cells (MSC) primary cultures were obtained from adipose tissue, bone marrow, and umbilical cord. Human chondrocytes were obtained from articular cartilage biopsies. In general, MSC expanded in the presence of Pl-s alone showed a low or no proliferation in comparison to cells grown with the combination of Pl-s and v-PL. Confluent, growth-arrested cells, either human MSC or human articular chondrocytes, treated with v-PL resumed proliferation, whereas control cultures, not supplemented with v-PL, remained quiescent and did not proliferate. Interestingly, signal transduction pathways distinctive of proliferation were activated also in cells treated with v-PL in the absence of serum, when cell proliferation did not occur, indicating that v-PL could induce the cell re-entry in the cell cycle (cell commitment), but the presence of serum proteins was an absolute requirement for cell proliferation to happen. Indeed, Pl-s alone supported cell growth in constitutively activated cell lines (U-937, HeLa, HaCaT, and V-79) regardless of the co-presence of v-PL. Plasma- and plasma-derived serum were equally able to sustain cell proliferation although, for cells cultured in adhesion, the Pl-s was more efficient than the plasma from which it was derived. In conclusion, the cells expanded in the presence of the new additives maintained their differentiation potential and did not show alterations in their karyotype. PMID:29209609

Pendulum Mass Affects the Measurement of Articular Friction Coefficient

PubMed Central

Akelman, Matthew R.; Teeple, Erin; Machan, Jason T.; Crisco, Joseph J.; Jay, Gregory D.; Fleming, Braden C.

2012-01-01

Friction measurements of articular cartilage are important to determine the relative tribologic contributions made by synovial fluid or cartilage, and to assess the efficacy of therapies for preventing the development of post-traumatic osteoarthritis. Stanton’s equation is the most frequently used formula for estimating the whole joint friction coefficient (μ) of an articular pendulum, and assumes pendulum energy loss through a mass-independent mechanism. This study examines if articular pendulum energy loss is indeed mass independent, and compares Stanton’s model to an alternative model, which incorporates viscous damping, for calculating μ. Ten loads (25-100% body weight) were applied in a random order to an articular pendulum using the knees of adult male Hartley guinea pigs (n = 4) as the fulcrum. Motion of the decaying pendulum was recorded and μ was estimated using two models: Stanton’s equation, and an exponential decay function incorporating a viscous damping coefficient. μ estimates decreased as mass increased for both models. Exponential decay model fit error values were 82% less than the Stanton model. These results indicate that μ decreases with increasing mass, and that an exponential decay model provides a better fit for articular pendulum data at all mass values. In conclusion, inter-study comparisons of articular pendulum μ values should not be made without recognizing the loads used, as μ values are mass dependent. PMID:23122223

Pendulum mass affects the measurement of articular friction coefficient.

PubMed

Akelman, Matthew R; Teeple, Erin; Machan, Jason T; Crisco, Joseph J; Jay, Gregory D; Fleming, Braden C

2013-02-01

Friction measurements of articular cartilage are important to determine the relative tribologic contributions made by synovial fluid or cartilage, and to assess the efficacy of therapies for preventing the development of post-traumatic osteoarthritis. Stanton's equation is the most frequently used formula for estimating the whole joint friction coefficient (μ) of an articular pendulum, and assumes pendulum energy loss through a mass-independent mechanism. This study examines if articular pendulum energy loss is indeed mass independent, and compares Stanton's model to an alternative model, which incorporates viscous damping, for calculating μ. Ten loads (25-100% body weight) were applied in a random order to an articular pendulum using the knees of adult male Hartley guinea pigs (n=4) as the fulcrum. Motion of the decaying pendulum was recorded and μ was estimated using two models: Stanton's equation, and an exponential decay function incorporating a viscous damping coefficient. μ estimates decreased as mass increased for both models. Exponential decay model fit error values were 82% less than the Stanton model. These results indicate that μ decreases with increasing mass, and that an exponential decay model provides a better fit for articular pendulum data at all mass values. In conclusion, inter-study comparisons of articular pendulum μ values should not be made without recognizing the loads used, as μ values are mass dependent. Copyright © 2012 Elsevier Ltd. All rights reserved.

Comparison of friction and wear of articular cartilage on different length scales.

PubMed

Kienle, Sandra; Boettcher, Kathrin; Wiegleb, Lorenz; Urban, Joanna; Burgkart, Rainer; Lieleg, Oliver; Hugel, Thorsten

2015-09-18

The exceptional tribological properties of articular cartilage are still far from being fully understood. Articular cartilage is able to withstand high loads and provide exceptionally low friction. Although the regeneration abilities of the tissue are very limited, it can last for many decades. These biomechanical properties are realized by an interplay of different lubrication and wear protection mechanisms. The deterioration of cartilage due to aging or injury leads to the development of osteoarthritis. A current treatment strategy focuses on supplementing the intra-articular fluid with a saline solution containing hyaluronic acid. In the work presented here, we investigated how changing the lubricating fluid affects friction and wear of articular cartilage, focusing on the boundary and mixed lubrication as well as interstitial fluid pressurization mechanisms. Different length and time scales were probed by atomic force microscopy, tribology and profilometry. We compared aqueous solutions with different NaCl concentrations to a viscosupplement containing hyaluronic acid (HA). In particular, we found that the presence of ions changes the frictional behavior and the wear resistance. In contrast, hyaluronic acid showed no significant impact on the friction coefficient, but considerably reduced wear. This study confirms the previous notion that friction and wear are not necessarily correlated in articular cartilage tribology and that the main role of HA might be to provide wear protection for the articular surface. Copyright © 2015 Elsevier Ltd. All rights reserved.

Articular Cartilage Repair of the Knee in Children and Adolescents

PubMed Central

Salzmann, Gian M.; Niemeyer, Philipp; Hochrein, Alfred; Stoddart, Martin J.; Angele, Peter

2018-01-01

Articular cartilage predominantly serves a biomechanical function, which begins in utero and further develops during growth and locomotion. With regard to its 2-tissue structure (chondrocytes and matrix), the regenerative potential of hyaline cartilage defects is limited. Children and adolescents are increasingly suffering from articular cartilage and osteochondral deficiencies. Traumatic incidents often result in damage to the joint surfaces, while repetitive microtrauma may cause osteochondritis dissecans. When compared with their adult counterparts, children and adolescents have a greater capacity to regenerate articular cartilage defects. Even so, articular cartilage injuries in this age group may predispose them to premature osteoarthritis. Consequently, surgery is indicated in young patients when conservative measures fail. The operative techniques for articular cartilage injuries traditionally performed in adults may be performed in children, although an individualized approach must be tailored according to patient and defect characteristics. Clear guidelines for defect dimension–associated techniques have not been reported. Knee joint dimensions must be considered and correlated with respect to the cartilage defect size. Particular attention must be given to the subchondral bone, which is frequently affected in children and adolescents. Articular cartilage repair techniques appear to be safe in this cohort of patients, and no differences in complication rates have been reported when compared with adult patients. Particularly, autologous chondrocyte implantation has good biological potential, especially for large-diameter joint surface defects. PMID:29568785

Notch signaling is involved in human articular chondrocytes de-differentiation during osteoarthritis.

PubMed

Sassi, Nadia; Gadgadi, Nadia; Laadhar, Lilia; Allouche, Mohamed; Mourali, Slim; Zandieh-Doulabi, Behrouz; Hamdoun, Moncef; Nulend, Jenneke Klein; Makni, Sondès; Sellami, Slaheddine

2014-02-01

During osteoarthritis (OA), chondrocytes undergo de-differentiation, resulting in the acquisition of a fibroblast-like morphology, decreased expression of collagen type II (colII) and aggrecan, and increased expression of collagen type I (colI), metalloproteinase 13 (MMP13) and nitric oxide synthase (eNOS). Notch signaling plays a crucial role during embryogenesis. Several studies showed that Notch is expressed in adulthood. The aim of our study was to confirm the involvement of Notch signaling in human OA at in vitro and ex vivo levels. Normal human articular chondrocytes were cultured during four passages either treated or not with a Notch inhibitor: DAPT. Human OA cartilage was cultured with DAPT for five days. Chondrocytes secreted markers and some Notch pathway components were analyzed using Western blotting and qPCR. Passaging chondrocytes induced a decrease in the cartilage markers: colII and aggrecan. DAPT-treated chondrocytes and OA cartilage showed a significant increase in healthy cartilage markers. De-differentiation markers, colI, MMP13 and eNOS, were significantly reduced in DAPT-treated chondrocytes and OA cartilage. Notch1 expression was proportional to colI, MMP13 and eNOS expression and inversely proportional to colII and aggrecan expression in nontreated cultured chondrocytes. Notch ligand: Jagged1 increased in chondrocytes culture. DAPT treatment resulted in reduced Jagged1 expression. Notch target gene HES1 increased during chondrocyte culture and was reduced when treated with DAPT. Targeting Notch signaling during OA might lead to the restitution of the typical chondrocyte phenotype and even to chondrocyte redifferentiation during the pathology.

What is the effect of matrices on cartilage repair? A systematic review.

PubMed

Wylie, James D; Hartley, Melissa K; Kapron, Ashley L; Aoki, Stephen K; Maak, Travis G

2015-05-01

Articular cartilage has minimal endogenous ability to undergo repair. Multiple chondral restoration strategies have been attempted with varied results. The purpose of our review was to determine: (1) Does articular chondrocyte transplantation or matrix-assisted articular chondrocyte transplantation provide better patient-reported outcomes scores, MRI morphologic measurements, or histologic quality of repair tissue compared with microfracture in prospective comparative studies of articular cartilage repair; and (2) which available matrices for matrix-assisted articular chondrocyte transplantation show the best patient-reported outcomes scores, MRI morphologic measurements, or histologic quality of repair tissue? We conducted a systematic review of PubMed, CINAHL, and MEDLINE from March 2004 to February 2014 using keywords determined to be important for articular cartilage repair, including "cartilage", "chondral", "cell source", "chondrocyte", "matrix", "augment", "articular", "joint", "repair", "treatment", "regeneration", and "restoration" to find articles related to cell-based articular cartilage repair of the knee. The articles were reviewed by two authors (JDW, MKH), our study exclusion criteria were applied, and articles were determined to be relevant (or not) to the research questions. The Methodological Index for Nonrandomized Studies (MINORS) scale was used to judge the quality of nonrandomized manuscripts used in this review and the Jadad score was used to judge the quality of randomized trials. Seventeen articles were reviewed for the first research question and 83 articles were reviewed in the second research question from 301 articles identified in the original systematic search. The average MINORS score was 9.9 (62%) for noncomparative studies and 16.1 (67%) for comparative studies. The average Jadad score was 2.3 for the randomized studies. Articular chondrocyte transplantation shows better patient-reported outcomes at 5 years in patients without chronic symptoms preoperatively compared with microfracture (p = 0.026). Matrix-assisted articular chondrocyte transplantation consistently showed improved patient-reported functional outcomes compared with microfracture (p values ranging from < 0.001 to 0.029). Hyalograft C(®) (Anika Therapeutics Inc, Bedford, MA, USA) and Chondro-gide(®) (Genzyme Biosurgery, Kastrup, Denmark) are the matrices with the most published evidence in the literature, but no studies comparing different matrices met our inclusion criteria, because the literature consists only of uncontrolled case series. Matrix-assisted articular chondrocyte transplantation leads to better patient-reported outcomes in cartilage repair compared with microfracture; however, future prospective research is needed comparing different matrices to determine which products optimize cartilage repair. Level IV, therapeutic study.

Identification of latexin by a proteomic analysis in rat normal articular cartilage

PubMed Central

2010-01-01

Background Osteoarthritis (OA) is characterized by degeneration of articular cartilage. Animal models of OA induced are a widely used tool in the study of the pathogenesis of disease. Several proteomic techniques for selective extraction of proteins have provided protein profiles of chondrocytes and secretory patterns in normal and osteoarthritic cartilage, including the discovery of new and promising biomarkers. In this proteomic analysis to study several proteins from rat normal articular cartilage, two-dimensional electrophoresis and mass spectrometry (MS) were used. Interestingly, latexin (LXN) was found. Using an immunohistochemical technique, it was possible to determine its localization within the chondrocytes from normal and osteoarthritic articular cartilage. Results In this study, 147 proteins were visualized, and 47 proteins were identified by MS. A significant proportion of proteins are involved in metabolic processes and energy (32%), as well as participating in different biological functions including structural organization (19%), signal transduction and molecular signaling (11%), redox homeostasis (9%), transcription and protein synthesis (6%), and transport (6%). The identified proteins were assigned to one or more subcellular compartments. Among the identified proteins, we found some proteins already recognized in other studies such as OA-associated proteins. Interestingly, we identified LXN, an inhibitor of mammalian carboxypeptidases, which had not been described in articular cartilage. Immunolabeling assays for LXN showed a granular distribution pattern in the cytoplasm of most chondrocytes of the middle, deep and calcified zones of normal articular cartilage as well as in subchondral bone. In osteoarthritic cartilage, LXN was observed in superficial and deep zones. Conclusions This study provides the first proteomic analysis of normal articular cartilage of rat. We identified LXN, whose location was demonstrated by immunolabeling in the chondrocytes from the middle, deep and calcified zones of normal articular cartilage, and superficial and deep zones of osteoarthritic cartilage. PMID:20525390

Intra-articular decorin influences the fibrosis genetic expression profile in a rabbit model of joint contracture.

PubMed

Abdel, M P; Morrey, M E; Barlow, J D; Grill, D E; Kolbert, C P; An, K N; Steinmann, S P; Morrey, B F; Sanchez-Sotelo, J

2014-01-01

The goal of this study was to determine whether intra-articular administration of the potentially anti-fibrotic agent decorin influences the expression of genes involved in the fibrotic cascade, and ultimately leads to less contracture, in an animal model. A total of 18 rabbits underwent an operation on their right knees to form contractures. Six limbs in group 1 received four intra-articular injections of decorin; six limbs in group 2 received four intra-articular injections of bovine serum albumin (BSA) over eight days; six limbs in group 3 received no injections. The contracted limbs of rabbits in group 1 were biomechanically and genetically compared with the contracted limbs of rabbits in groups 2 and 3, with the use of a calibrated joint measuring device and custom microarray, respectively. There was no statistical difference in the flexion contracture angles between those limbs that received intra-articular decorin versus those that received intra-articular BSA (66° vs 69°; p = 0.41). Likewise, there was no statistical difference between those limbs that received intra-articular decorin versus those who had no injection (66° vs 72°; p = 0.27). When compared with BSA, decorin led to a statistically significant increase in the mRNA expression of 12 genes (p < 0.01). In addition, there was a statistical change in the mRNA expression of three genes, when compared with those without injection. In this model, when administered intra-articularly at eight weeks, 2 mg of decorin had no significant effect on joint contractures. However, our genetic analysis revealed a significant alteration in several fibrotic genes. Cite this article: Bone Joint Res 2014;3:82-8.

Arthroscopic findings of a diagnostic dilemma- hip pathology with normal imaging.

PubMed

Buikstra, Joel Glenn; Fary, Camdon; Tran, Phong

2017-03-21

Patients with groin, hip and pelvic pain but normal findings on MRI and minimal changes on x-ray can be a diagnostic problem. This paper looks at the arthroscopic findings of patients who have had hip pain and a positive response to an intra-articular anaesthetic but have non-contributory imaging. We hypothesized that standard MRI's were missing significant pathology and if there was a response to intra-articular local anaesthesia, pathology found during arthroscopy was likely. A retrospective review of all hip arthroscopies performed from March 2011 to January 2015 by two orthopaedic surgeons specializing in hip arthroscopy was conducted to identify patients with clinically suspected intra-articular hip pathology despite a normal MRI report and X-ray. Clinical suspicion of intra-articular hip pathology was confirmed with a positive response to a fluoroscopically guided intra-articular injection of local anaesthetic and corticosteroid. Pathologic findings were collated from the standardised operative notes. Fifty-three hip arthroscopies performed in 51 patients met the inclusion criteria from a total of 1348 hip arthroscopies performed over a 46-month period. All but one of the 53 (98%) hips had arthroscopically confirmed pathology. Mean patient age was 32.5 years [15 to 67 years] with 40 (78%) females and 11 (22%) males. 92.5% of the hips (49/53) were FADIR (flexion, adduction and internal rotation) positive on clinical examination, giving this test a positive predictive value of 98% (95% CI: 89.31 to 99.67%) for intra-articular pathology. In patients with a normal MRI without contrast and a positive response (relief of pain) to an intra-articular injection that failed conservative management, there is a 98% chance of intra-articular hip pathology being discovered on hip arthroscopy.

Preemptive Analgesia in Hip Arthroscopy: A Randomized Controlled Trial of Preemptive Periacetabular or Intra-articular Bupivacaine in Addition to Postoperative Intra-articular Bupivacaine.

PubMed

Shlaifer, Amir; Sharfman, Zachary Tuvya; Martin, Hal David; Amar, Eyal; Kazum, Efi; Warschawski, Yaniv; Paret, Matan; Brill, Silviu; Drexler, Michael; Rath, Ehud

2017-01-01

To evaluate and compare the efficacy of intra-articular and periacetabular blocks for postoperative pain control after hip arthroscopy. Forty-two consecutive patients scheduled for hip arthroscopy were randomized into 2 postoperative pain control groups. One group received preemptive intra-articular 20 mL of bupivacaine 0.5% injection, and the second group received preemptive periacetabular 20 mL of bupivacaine 0.5% injection. Before closure all patients received an additional dose of 20 mL of bupivacaine 0.5% intra-articularly. Data were compared with respect to postoperative pain with visual analog scale (VAS) and analgesic consumption, documented in a pain diary for 2 weeks after surgery. Twenty-one patients were treated with intra-articular injection, and 21 patients with peri-acetabular injection. There were no significant differences with regards to patient demographics or surgical procedures. VAS scores recorded during the first 30 minutes postoperatively and 18 hours after surgery were significantly lower in the periacetabular group compared with in the intra-articular group (0.667 ± 1.49 vs 2.11 ± 2.29; P < .045 and 2.62 ± 2.2 vs 4.79 ± 2.6; P < .009). There were no differences between the groups with regard to analgesic consumption. Periacetabular injection of bupivacaine 0.5% was superior to intra-articular injection in pain reduction after hip arthroscopy at 30 minutes and 18 hours postoperatively. However, total analgesic consumption over the first 2 postoperative weeks and VAS pain measurements were not significantly affected. Level I, randomized controlled trial. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Indentation mapping revealed poroelastic, but not viscoelastic, properties spanning native zonal articular cartilage.

PubMed

Wahlquist, Joseph A; DelRio, Frank W; Randolph, Mark A; Aziz, Aaron H; Heveran, Chelsea M; Bryant, Stephanie J; Neu, Corey P; Ferguson, Virginia L

2017-12-01

Osteoarthrosis is a debilitating disease affecting millions, yet engineering materials for cartilage regeneration has proven difficult because of the complex microstructure of this tissue. Articular cartilage, like many biological tissues, produces a time-dependent response to mechanical load that is critical to cell's physiological function in part due to solid and fluid phase interactions and property variations across multiple length scales. Recreating the time-dependent strain and fluid flow may be critical for successfully engineering replacement tissues but thus far has largely been neglected. Here, microindentation is used to accomplish three objectives: (1) quantify a material's time-dependent mechanical response, (2) map material properties at a cellular relevant length scale throughout zonal articular cartilage and (3) elucidate the underlying viscoelastic, poroelastic, and nonlinear poroelastic causes of deformation in articular cartilage. Untreated and trypsin-treated cartilage was sectioned perpendicular to the articular surface and indentation was used to evaluate properties throughout zonal cartilage on the cut surface. The experimental results demonstrated that within all cartilage zones, the mechanical response was well represented by a model assuming nonlinear biphasic behavior and did not follow conventional viscoelastic or linear poroelastic models. Additionally, 10% (w/w) agarose was tested and, as anticipated, behaved as a linear poroelastic material. The approach outlined here provides a method, applicable to many tissues and biomaterials, which reveals and quantifies the underlying causes of time-dependent deformation, elucidates key aspects of material structure and function, and that can be used to provide important inputs for computational models and targets for tissue engineering. Elucidating the time-dependent mechanical behavior of cartilage, and other biological materials, is critical to adequately recapitulate native mechanosensory cues for cells. We used microindentation to map the time-dependent properties of untreated and trypsin treated cartilage throughout each cartilage zone. Unlike conventional approaches that combine viscoelastic and poroelastic behaviors into a single framework, we deconvoluted the mechanical response into separate contributions to time-dependent behavior. Poroelastic effects in all cartilage zones dominated the time-dependent behavior of articular cartilage, and a model that incorporates tension-compression nonlinearity best represented cartilage mechanical behavior. These results can be used to assess the success of regeneration and repair approaches, as design targets for tissue engineering, and for development of accurate computational models. Copyright © 2017 Acta Materialia Inc. All rights reserved.

Physiotherapy co-management of rheumatoid arthritis: identification of red flags, significance to clinical practice and management pathways.

PubMed

Briggs, Andrew M; Fary, Robyn E; Slater, Helen; Ranelli, Sonia; Chan, Madelynn

2013-12-01

Rheumatoid arthritis (RA) is a chronic, systemic, autoimmune disease. Physiotherapy interventions for people with RA are predominantly targeted at ameliorating disability resulting from articular and peri-articular manifestations of the disease and providing advice and education to improve functional capacity and quality of life. To ensure safe and effective care, it is critical that physiotherapists are able to identify potentially serious articular and peri-articular manifestations of RA, such as instability of the cervical spine. Additionally, as primary contact professionals, it is essential that physiotherapists are aware of the potentially serious extra-articular manifestations of RA. This paper provides an overview of the practice-relevant manifestations associated with RA that might warrant further investigation by a medical practitioner (red flags), their relevance to physiotherapy practice, and recommended management pathways. Copyright © 2013 Elsevier Ltd. All rights reserved.

Relationship between intraosseous pressures and intra-articular pressure in arthritis of the knee. An experimental study in immature dogs.

PubMed

Bünger, C; Harving, S; Hjermind, J; Bünger, E H

1983-04-01

The influence of chronic synovial inflammation and effusion on the juxta-articular bone haemodynamics in the juvenile knee was studied in 12 immature dogs with Carragheenin-induced unilateral arthritis. Using a fluid filled electromanometric pressure recording system simultaneous pressure measurements were taken from the distal femoral metaphysis, juxta-articular epiphyses and knee joint cavity in general anaesthesia followed by intraosseous phlebographies. During resting conditions the intraosseous pressure of the distal femoral epiphysis and the intra-articular pressure was significantly elevated. The phlebographies showed increased accumulation of contrast in arthritic femoral epiphyses with decreased contrast clearance rate. During increasing intra-articular pressure an augmented vulnerability of the blood supply of the arthritic femoral epiphyses was demonstrated. The results suggests that joint effusion may play an important role in the bone changes in juvenile degenerative arthritis of the knee.

Gene Therapy for Osteoarthritis: Pharmacokinetics of Intra-articular scAAV.IL-1Ra Delivery in an Equine Model.

PubMed

Watson Levings, Rachael; Broome, Ted A; Smith, Andrew D; Rice, Brett L; Gibbs, Eric P; Myara, D Alex; Hyddmark, E Viktoria; Nasri, Elham; Zarezadeh, Ali; Levings, Padraic P; Lu, Yuan; Dacanay, E Anthony; Foremny, Gregory B; Evans, Christopher H; Morton, Alison J; Winter, Mathew; Dark, Michael J; Nickerson, David M; Colahan, Patrick T; Ghivizzani, Steven Craig

2018-06-05

142: Toward the treatment of osteoarthritis (OA), we have been investigating self-complementary adeno-associated virus (scAAV) for intra-articular delivery of gene products with therapeutic potential. As OA frequently affects weight-bearing joints, we performed pharmacokinetic studies in the equine forelimb to identify parameters of scAAV gene delivery relevant to clinical translation. Using the coding sequence for interleukin-1 receptor antagonist (IL-1Ra) as a secreted therapeutic reporter we first generated an scAAV vector containing an optimized cDNA for equine IL-1Ra. In dosing studies in vivo we identified a putative ceiling dose of 5 x 1012 viral genomes (vg) which elevated the steady-state eqIL-1Ra in synovial fluids >50-fold for over 6 months. No adverse effects of treatment were seen, and eqIL-1Ra in serum and urine remained at background. Using 5 x 1012 vg and GFP as a cytologic marker, we compared the local and systemic distribution of vector and transduced cells in healthy joints and those with late stage, naturally-occurring OA. Strikingly, a substantial increase in transgenic expression was associated with the articular pathologies characteristic of OA, including synovitis, osteophyte formation and damaged cartilage. Nonetheless, in both the healthy and OA environments the vector and transgene expression were effectively contained within the injected joint. 143: We are investigating self-complementary adeno-associated virus (scAAV) as a vector for intra-articular gene-delivery of IL-1Ra, and its therapeutic capacity in the treatment of osteoarthritis (OA). To model gene-transfer on a scale proportional to the human knee, a frequent site of OA incidence, we focused our studies on the joints of the equine forelimb. Using AAV2.5 capsid and equine IL-1Ra as a homologous transgene, we previously identified a functional ceiling dose of ~5 x 1012 viral genomes, which elevated the steady state levels of eqIL-1Ra in synovial fluids by more than 40-fold over endogenous production for at least 6 months. Here, using an osteochondral fragmentation model of early OA, we examined the functional capacity of scAAV.IL-1Ra gene-delivery in equine joints over a period of 12 weeks. In the disease model, transgenic eqIL-1Ra expression was several-fold higher than seen previously in healthy joints, and correlated directly with the severity of joint pathology at the time of treatment. Despite wide variation in expression, the steady-state eqIL-1Ra in synovial fluids exceeded that of IL-1 by > 400-fold in all animals, and a consistent treatment effect was observed. This included a 30-40% reduction in lameness and ~25% improvement in total joint pathology by both MRI and arthroscopic assessments, which included reduced joint effusion and synovitis, and improved repair of the osteochondral lesion. No vector-related increase in eqIL-1Ra levels in blood or urine was noted. Cumulatively our studies in the equine model indicate scAAV.IL-1Ra administration is reasonably safe and capable of sustained therapeutic IL-1Ra production intra-articularly in joints of human scale. This profile supports consideration for human testing in OA.

Chondromalacia induced by patellar subluxation: morphological and morphometrical aspects in rabbits.

PubMed

Sant'Anna, M M S; Apfel, M I R

2002-01-01

The purpose of this study was to describe morphologically and quantify the changes of the articular cartilage in chondromalacia, concerning both the chondrocytes and extracellular matrix. Eight rabbits were submitted daily to patellar subluxation, causing chondromalacia after two weeks. The knee fragments obtained were processed by the standard methods. These experimental conditions caused degenerative alterations of the articular cartilage, varying from a slight decrease of proteoglycans, to fibrillations, clefts, and horizontal splitting. The results showed a significantly increase number of chondrocytes (p < 0,000139), although smaller in size (p < 0,000109). The immobilization for 2 weeks and the intermittent passive daily motion afterwards for a period of 2 weeks, was effective to cause patellar chrondomalacia in rabbits.

[The occurance lead and cadmium in hip joint in aspect of exposure on tobacco smoke].

PubMed

Bogunia, Mariusz; Brodziak-Dopierała, Barbara; Kwapuliński, Jerzy; Ahnert, Bozena; Kowol, Jolanta; Nogaj, Ewa

2008-01-01

The objective of this study was qualification of content cadmium and lead in selected elements of the hip joint in aspect of tobacco smoking. The material for the research were 5 elements of hip joint (articular cartilage, trabecular bone and cortical bone femur head, fragment articular capsule and fragment trabecular bone from region intertrochanteric femoral bone), obtained intraoperatively during endoprothesoplastic surgeries. The samples come from habitants of Upper Silesian Region. Determination of trace elements contents were performed by ASA method (Pye Unicam SP-9) in acetylene-oxygen flame. Higher contents of lead were observed for smoking people, however in case of cadmium the differences of this element were not statistical essential between smokers and non-smokers.

Seven diverse human embryonic stem cell-derived chondrogenic clonal embryonic progenitor cell lines display site-specific cell fates.

PubMed

Sternberg, Hal; Kidd, Jennifer; Murai, James T; Jiang, Jianjie; Rinon, Ariel; Erickson, Isaac E; Funk, Walter D; Wang, Qian; Chapman, Karen B; Vangsness, C Thomas; West, Michael D

2013-03-01

The transcriptomes of seven diverse clonal human embryonic progenitor cell lines with chondrogenic potential were compared with that of bone marrow-derived mesenchymal stem cells (MSCs). The cell lines 4D20.8, 7PEND24, 7SMOO32, E15, MEL2, SK11 and SM30 were compared with MSCs using immunohistochemical methods, gene expression microarrays and quantitative real-time PCR. In the undifferentiated progenitor state, each line displayed unique combinations of site-specific markers, including AJAP1, ALDH1A2, BMP5, BARX1, HAND2, HOXB2, LHX1, LHX8, PITX1, TBX15 and ZIC2, but none of the lines expressed the MSC marker CD74. The lines showed diverse responses when differentiated in the presence of combinations of TGF-β3, BMP2, 4, 6 and 7 and GDF5, with the lines 4D20.8, SK11, SM30 and MEL2 showing osteogenic markers in some differentiation conditions. The line 7PEND24 showed evidence of regenerating articular cartilage and, in some conditions, markers of tendon differentiation. The scalability of site-specific clonal human embryonic stem cell-derived embryonic progenitor cell lines may provide novel models for the study of differentiation and methods for preparing purified and identified cells types for use in therapy.

Evaluation of the effects of dexketoprofen trometamol on knee joınt: an in vivo & in vitro study

PubMed Central

Sagir, Ozlem; Sunay, Fatma Bahar; Yildirim, Hatice; Aksoz, Elif; Ozaslan, Sabri; Koroglu, Ahmet; Aydemir, Tugsen; Ulusal, Ali Engin; Kockar, Feray

2013-01-01

Background & objectives: Intra-articular (ia) injections of local anaesthetics and non-steroidal anti-inflammatory drugs (NSAID's) are simple and efficient to ensure post-operative analgesia but some of these have toxic effects on the synovium and cartilage. Dexketoprofen is recently introduced S-enantiomer of ketoprofen with a better analgesic and side effect profile. This study was done to evaluate the possible toxic effects of dexketoprofen trometamol on knee joint cartilage and symovium in vitro and in vivo. Methods: Forty one Sprague-Dawley rats were anaesthetized by ketamine. Dexketoprofen trometamol (0.25 ml) was injected into the right knee joint of the 35 rats and 0.25 ml serum physiologic into the left knee joint of the same animals. Six rats were sham operated. Thirty five animals were randomly divided into five equal groups. Seven animals were sacrified at 24th, 48th hours and 7th, 14th, and 21st days of the injections. Haematoxylin eosin stained sections from the knee joints were evaluated for the signs of inflammation according to five point scale. Primary chondrocytes were isolated from the articular cartilages of rats for in vitro studies. Cells were exposed to 0.25 ml dexketoprofen trometamol or 0.25 ml dexketoprofen medium mixture at 1:1 ratio for 15, 30, 45 and 60 min. Cell viability was determined by 3-(4, 5- dimethylthiazole-2-yl)-2.5-diphenyl tetrazolium bromide (MTT) assay, 24, 48 and 72 h after drug treatment. Results: No significant histopathologic differences were found between dexketoprofen trometamol and physiologic serum (control) applied joints at all time intervals in in vivo study. Cell proliferation in dexketoprofen trometamol treated chondrocytes was inhibited for all time intervals compared to control. In dexketoprofen-medium mixture groups significant differences were only seen 24 h after the 30 and 45 min application of medium: drug mixture. Interpretation & conclusions: Intra-articular application of dexketoprofen trometamol into the rat knee joints did not cause significant histopathological changes, but its in vitro application in primary chondrocyte culture caused significant cytotoxicity. The effects of dexketoprofen at different concentrations need to be further investigated in culture of rat and human chondrocytes. PMID:24521635

Morphometric Study of Clavicular Facet of Coracoclavicular Joint in Adult Indian Population

PubMed Central

Mahajan, Anita; Vasudeva, Neelam

2016-01-01

Introduction Anthropologists have used Coracoclavicular Joint (CCJ), a non-metric anatomical variant in population, as a marker for population migration from prehistoric times to present. Aim The aim of this osteological study was to determine the incidence and morphometry of articular facet of CCJ on conoid tubercle of clavicle in Indian population, as Indian studies are scanty and incomplete. Materials and Methods The study was done on 144 adult human clavicles (76 right and 68 left; 93 males and 51 females) collected from osteology museum in Department of Anatomy, Maulana Azad Medical College, New Delhi, India. The presence of articular facet on the conoid tubercle was determined and Maximum Antero-Posterior (MAPD) and maximum transverse diameter (MTD) was measured by digital vernier calliper. The incidence was compared on the basis of sex, side and with other osteological studies in the world. Statistical analysis was done using the Chi-Square test for nominal categorical data and student’s t-test for normally distributed continuous variables in Microsoft Excel 2007 to assess the relationship between the examined variables. Results Articular facet on conoid tubercle was found in 8 cases (5.6%). Seven (9.2%) were present on the right side and one (1.5%) on the left side. Seven cases (7.5%) were present in males and one case (2%) was found in females. The facets were generally oval, with MAPD and MTD of 12.28 and 17.17 mm respectively. A significant side variation was present with right sided facet being more common. The left sided facet was more transversely elongated than right. In males, the facets were more elongated antero-posteriorly than in females. Conclusion The Indian population showed an incidence of 5.6%, which was comparable to other ethnic groups in world population. The morphometric and side differences could be attributed to the occupational factors and range of movements associated with the CCJ. The CCJ should be borne in mind as a differential diagnosis for thoracic outlet syndrome and in general for shoulder pain. PMID:27190785

Surgical Indications and Technique for Anterior Cruciate Ligament Reconstruction Combined with Lateral Extra-articular Tenodesis or Anterolateral Ligament Reconstruction.

PubMed

Vundelinckx, Bart; Herman, Benjamin; Getgood, Alan; Litchfield, Robert

2017-01-01

After anterior cruciate ligament (ACL) rupture, anteroposterior and rotational laxity in the knee causes instability, functional symptoms, and damage to other intra-articular structures. Surgical reconstruction aims to restore the stability in the knee, and to improve function and ability to participate in sports. It also protects cartilage and menisci from secondary injuries. Because of persistent rotational instability after ACL reconstruction, combined intra-articular and extra-articular procedures are more commonly performed. In this article, an overview of anatomy, biomechanical studies, current gold standard procedures, techniques, and research topics are summarized. Copyright © 2016 Elsevier Inc. All rights reserved.

Complications of intra-articular injections of triamcinolone hexacetonide in chronic arthritis in children.

PubMed

Job-Deslandre, C; Menkes, C J

1990-01-01

Intra-articular injections of triamcinolone hexacetonide (THA) are a useful therapy in JRA and HLA B 27 related arthritis (B 27 RA). Published data have indicated good results and few side effects. We evaluate here the frequency of occurrence of local side effects in 35 children with JRA (115 joints treated) and 13 children with B 27 RA (29 joints treated). With a mean follow up of 25 months in JRA and 18 months in B 27 RA, we observed 12 cases (8.3%) of subcutaneous tissue atrophy with local depigmentation (knees 5 cases, wrists 2 cases, ankles 3 cases, metatarsophalangeal joints 2 cases) and 7 cases (4.9%) of intra-articular calcifications all in the JRA group (wrists 3 cases, knees 2 cases, ankles 2 cases). Youth and joint size are possible predisposing factors for subcutaneous tissue atrophy and intra-articular calcification. Spontaneous improvement previously reported for these local side effects was not observed in our study. These results underline the necessity of discussing on a case by case basis whether intra-articular, non long-acting corticosteroid or THA are indicated. THA must be injected with a rigorous technique and with a dosage adapted to the articular volume.

Comparative Effect of Physicomechanical and Biomolecular Cues on Zone-Specific Chondrogenic Differentiation of Mesenchymal Stem Cells

PubMed Central

Moeinzadeh, Seyedsina; Shariati, Seyed Ramin Pajoum; Jabbari, Esmaiel

2016-01-01

Current tissue engineering approaches to regeneration of articular cartilage rarely restore the tissue to its normal state because the generated tissue lacks the intricate zonal organization of the native cartilage. Zonal regeneration of articular cartilage is hampered by the lack of knowledge for the relation between physical, mechanical, and biomolecular cues and zone-specific chondrogenic differentiation of progenitor cells. This work investigated in 3D the effect of TGF-β1, zone-specific growth factors, optimum matrix stiffness, and adding nanofibers on the expression of chondrogenic markers specific to the superficial, middle, and calcified zones of articular cartilage by the differentiating human mesenchymal stem cells (hMSCs). Growth factors included BMP-7, IGF-1, and hydroxyapatite (HA) for the superficial, middle, and calcified zones, respectively; optimum matrix stiffness was 80 kPa, 2.1 MPa, and 320 MPa; and nanofibers were aligned horizontal, random, and perpendicular to the gel surface. hMSCs with zone-specific cell densities were encapsulated in engineered hydrogels and cultured with or without TGF-β1, zone-specific growth factor, optimum matrix modulus, and fiber addition and cultured in basic chondrogenic medium. The expression of encapsulated cells was measured by mRNA, protein, and biochemical analysis. Results indicated that zone-specific matrix stiffness had a dominating effect on chondrogenic differentiation of hMSCs to the superficial and calcified zone phenotypes. Addition of aligned nanofibers parallel to the direction of gel surface significantly enhanced expression of Col II in the superficial zone chondrogenic differentiation of hMSCs. Conversely, biomolecular factor IGF-1 in combination with TGF-β1 had a dominating effect on the middle zone chondrogenic differentiation of hMSCs. Results of this work could potentially lead to the development of multilayer grafts mimicking the zonal organization of articular cartilage. PMID:27038568

Comparative analysis of gene expression profiles of hip articular cartilage between non-traumatic necrosis and osteoarthritis.

PubMed

Wang, Wenyu; Liu, Yang; Hao, Jingcan; Zheng, Shuyu; Wen, Yan; Xiao, Xiao; He, Awen; Fan, Qianrui; Zhang, Feng; Liu, Ruiyu

2016-10-10

Hip cartilage destruction is consistently observed in the non-traumatic osteonecrosis of femoral head (NOFH) and accelerates its bone necrosis. The molecular mechanism underlying the cartilage damage of NOFH remains elusive. In this study, we conducted a systematically comparative study of gene expression profiles between NOFH and osteoarthritis (OA). Hip articular cartilage specimens were collected from 12 NOFH patients and 12 controls with traumatic femoral neck fracture for microarray (n=4) and quantitative real-time PCR validation experiments (n=8). Gene expression profiling of articular cartilage was performed using Agilent Human 4×44K Microarray chip. The accuracy of microarray experiment was further validated by qRT-PCR. Gene expression results of OA hip cartilage were derived from previously published study. Significance Analysis of Microarrays (SAM) software was applied for identifying differently expressed genes. Gene ontology (GO) and pathway enrichment analysis were conducted by Gene Set Enrichment Analysis software and DAVID tool, respectively. Totally, 27 differently expressed genes were identified for NOFH. Comparing the gene expression profiles of NOFH cartilage and OA cartilage detected 8 common differently expressed genes, including COL5A1, OGN, ANGPTL4, CRIP1, NFIL3, METRNL, ID2 and STEAP1. GO comparative analysis identified 10 common significant GO terms, mainly implicated in apoptosis and development process. Pathway comparative analysis observed that ECM-receptor interaction pathway and focal adhesion pathway were enriched in the differently expressed genes of both NOFH and hip OA. In conclusion, we identified a set of differently expressed genes, GO and pathways for NOFH articular destruction, some of which were also involved in the hip OA. Our study results may help to reveal the pathogenetic similarities and differences of cartilage damage of NOFH and hip OA. Copyright © 2016 Elsevier B.V. All rights reserved.

Pre-Treatment of Human Mesenchymal Stem Cells With Inflammatory Factors or Hypoxia Does Not Influence Migration to Osteoarthritic Cartilage and Synovium.

PubMed

Leijs, Maarten J C; van Buul, Gerben M; Verhaar, Jan A N; Hoogduijn, Martin J; Bos, Pieter K; van Osch, Gerjo J V M

2017-04-01

Mesenchymal stem cells (MSCs) are promising candidates as a cell-based therapy for osteoarthritis (OA), although current results are modest. Pre-treatment of MSCs before application might improve their therapeutic efficacy. Pre-treatment of MSCs with inflammatory factors or hypoxia will improve their migration and adhesion capacities toward OA-affected tissues. Controlled laboratory study. We used real-time polymerase chain reaction to determine the effects of different fetal calf serum (FCS) batches, platelet lysate (PL), hypoxia, inflammatory factors, factors secreted by OA tissues, and OA synovial fluid (SF) on the expression of 12 genes encoding chemokine or adhesion receptors. Migration of MSCs toward factors secreted by OA tissues was studied in vitro, and attachment of injected MSCs was evaluated in vivo in healthy and OA knees of male Wistar rats. Different FCS batches, PL, or hypoxia did not influence the expression of the migration and adhesion receptor genes. Exposure to inflammatory factors altered the expression of CCR1, CCR4, CD44, PDGFRα, and PDGFRβ. MSCs migrated toward factors secreted by OA tissues in vitro. Neither pre-treatment with inflammatory factors nor the presence of OA influenced MSC migration in vitro or adhesion in vivo. Factors secreted by OA tissues increase MSC migration in vitro. In vivo, no difference in MSC adhesion was found between OA and healthy knees. Pre-treatment with inflammatory factors influenced the expression of migration and adhesion receptors of MSCs but not their migration in vitro or adhesion in vivo. To improve the therapeutic capacity of intra-articular injection of MSCs, they need to remain intra-articular for a longer period of time. Pre-treatment of MSCs with hypoxia or inflammatory factors did not increase the migration or adhesion capacity of MSCs and will therefore not likely prolong their intra-articular longevity. Alternative approaches to prolong the intra-articular presence of MSCs should be developed to increase the therapeutic effect of MSCs in OA.

Benefits of Ilizarov automated bone distraction for nerves and articular cartilage in experimental leg lengthening.

PubMed

Shchudlo, Nathalia; Varsegova, Tatyana; Stupina, Tatyana; Shchudlo, Michael; Saifutdinov, Marat; Yemanov, Andrey

2017-09-18

To determine peculiarities of tissue responses to manual and automated Ilizarov bone distraction in nerves and articular cartilage. Twenty-nine dogs were divided in two experimental groups: Group M - leg lengthening with manual distraction (1 mm/d in 4 steps), Group A - automated distraction (1 mm/d in 60 steps) and intact group. Animals were euthanized at the end of distraction, at 30 th day of fixation in apparatus and 30 d after the fixator removal. M-responses in gastrocnemius and tibialis anterior muscles were recorded, numerical histology of peroneal and tibialis nerves and knee cartilage semi-thin sections, scanning electron microscopy and X-ray electron probe microanalysis were performed. Better restoration of M-response amplitudes in leg muscles was noted in A-group. Fibrosis of epineurium with adipocytes loss in peroneal nerve, subperineurial edema and fibrosis of endoneurium in some fascicles of both nerves were noted only in M-group, shares of nerve fibers with atrophic and degenerative changes were bigger in M-group than in A-group. At the end of experiment morphometric parameters of nerve fibers in peroneal nerve were comparable with intact nerve only in A-group. Quantitative parameters of articular cartilage (thickness, volumetric densities of chondrocytes, percentages of isogenic clusters and empty cellular lacunas, contents of sulfur and calcium) were badly changed in M-group and less changed in A-group. Automated Ilizarov distraction is more safe method of orthopedic leg lengthening than manual distraction in points of nervous fibers survival and articular cartilage arthrotic changes.

Optical clearing of articular cartilage: a comparison of clearing agents

NASA Astrophysics Data System (ADS)

Bykov, Alexander; Hautala, Tapio; Kinnunen, Matti; Popov, Alexey; Karhula, Sakari; Saarakkala, Simo; Nieminen, Miika T.; Tuchin, Valery

2015-07-01

Optical clearing technique was applied to the problem of OCT imaging of articular cartilage and subchondral bone. We show that optical clearing significantly enhances visualization of articular cartilage and cartilage-bone interface. The effect of different clearing agents was analyzed. For the clearing, iohexol solution and propylene glycol (PG) were used. Clearing was performed in vitro at room temperature by immersion method. Cylindrical osteochondral samples (d=4.8mm) were drilled from bovine lateral femur and stored in phosphate-buffered saline at -20°C until clearing. Monitoring of clearing process was performed using high-speed spectral-domain OCT system providing axial resolution of 5.8μm at 930nm. Total duration of experiment was 90-100min to ensure saturation of clearing. We have shown that iohexol solution and PG are capable to optically clear articular cartilage enabling reliable characterization of cartilagebone interface with OCT. Being a low osmolarity agent, iohexol provides minimal changes to the thickness of cartilage sample. Clearing saturation time for the cartilage sample with the thickness of 0.9 mm measured with OCT is of 50 min. However, less than 15 min is enough to reliably detect the rear cartilage boundary. Alternatively, PG significantly (60%) reduces the cartilage thickness enabling better visualization of subchondral bone. It was observed that PG has higher clearing rate. The clearing saturation time is of 30 min, however less than 5 min is enough to detect cartilage-bone interface. We conclude that iohexol solution is superior for OCT imaging of cartilage and cartilage-bone interface, while PG suits better for subhondral bone visualization.

Aquarium Portal Technique for PASTA Lesion Repair.

PubMed

Meyer, Dominik C; Gerber, Christian; Familiari, Filippo

2017-10-01

The simultaneous arthroscopic exposure of the subacromial and intra-articular space of the shoulder is challenging in the presence of only partial-thickness rotator cuff tears. We present our experience and method of entering the joint through the opened rotator cuff interval from an anterosuperior portal between the coracoid process and anterior acromion. With moderate (approximately 30°) abduction and external rotation, the rotator interval opens readily, offering a view with the camera toward the anterior edge of the supraspinatus tendon. An anterior view on the anterior leading edge of the supraspinatus tendon is obtained, showing the subacromial space above and the glenohumeral space below the tendon, similar to the view in an aquarium. The rotator cuff can be elevated using a rod inserted intra-articularly from posterior, whereas anchors and other instruments may be inserted from lateral. This approach offers the advantages of full exposure of the posterior undersurface of the rotator cuff insertion; a convenient approximately 90° angle between the camera and instruments; and no need to change portals for anchor placement, tendon stitching, or suture handling. The objective of this Technical Note is to describe our arthroscopic repair approach (aquarium technique) to PASTA (partial articular supraspinatus tendon avulsion) lesions.

Intra-articular calcaneal fractures: effect of open reduction and internal fixation on the contact characteristics of the subtalar joint.

PubMed

Mulcahy, D M; McCormack, D M; Stephens, M M

1998-12-01

Intra-articular calcaneal fractures are associated with significant long-term morbidity, and considerable controversy exists regarding the optimum method of treating them. The contact characteristics in the intact subtalar joint were determined at known loads and for different positions of the ankle and subtalar joint, using pressure-sensitive film (Super Low; Fuji, Itochu Canada Ltd, Montreal, Quebec). We measured the contact area to joint area ratio (pressure > 5 kg force/cm2 [kgf/cm2]) which normalizes for differences in joint size and the ratio of high pressure zone (>20 kgf/cm2) as a reflection of overall increase in joint pressure. Three simulated fracture patterns were then created and stabilized with either 1 or 2 mm of articular incongruity. Eight specimens were prepared with a primary fracture line through the posterior facet, eight with a joint depression-type fracture, and six with a central joint depression fracture. A measure of 1 to 2 mm of incongruity in the posterior facet for all three fracture patterns produced significant unloading of the depressed fragment, with a redistribution of the overall pattern of pressure distribution to parts of the facet that were previously unloaded.

The potential of IGF-1 and TGFbeta1 for promoting "adult" articular cartilage repair: an in vitro study.

PubMed

Davies, Lindsay C; Blain, Emma J; Gilbert, Sophie J; Caterson, Bruce; Duance, Victor C

2008-07-01

Research into articular cartilage repair, a tissue unable to spontaneously regenerate once injured, has focused on the generation of a biomechanically functional repair tissue with the characteristics of hyaline cartilage. This study was undertaken to provide insight into how to improve ex vivo chondrocyte amplification, without cellular dedifferentiation for cell-based methods of cartilage repair. We investigated the effects of insulin-like growth factor 1 (IGF-1) and transforming growth factor beta 1 (TGFbeta1) on cell proliferation and the de novo synthesis of sulfated glycosaminoglycans and collagen in chondrocytes isolated from skeletally mature bovine articular cartilage, whilst maintaining their chondrocytic phenotype. Here we demonstrate that mature differentiated chondrocytes respond to growth factor stimulation to promote de novo synthesis of matrix macromolecules. Additionally, chondrocytes stimulated with IGF-1 or TGFbeta1 induced receptor expression. We conclude that IGF-1 and TGFbeta1 in addition to autoregulatory effects have differential effects on each other when used in combination. This may be mediated by regulation of receptor expression or endogenous factors; these findings offer further options for improving strategies for repair of cartilage defects.

Permeability and shear modulus of articular cartilage in growing mice.

PubMed

Berteau, J-Ph; Oyen, M; Shefelbine, S J

2016-02-01

Articular cartilage maturation is the postnatal development process that adapts joint surfaces to their site-specific biomechanical demands. Understanding the changes in mechanical tissues properties during growth is a critical step in advancing strategies for orthopedics and for cell- and biomaterial- based therapies dedicated to cartilage repair. We hypothesize that at the microscale, the articular cartilage tissue properties of the mouse (i.e., shear modulus and permeability) change with the growth and are dependent on location within the joint. We tested cartilage on the medial femoral condyle and lateral femoral condyle of seven C57Bl6 mice at different ages (2, 3, 5, 7, 9, 12, and 17 weeks old) using a micro-indentation test. Results indicated that permeability decreased with age from 2 to 17 weeks. Shear modulus reached a peak at the end of the growth (9 weeks). Within an age group, shear modulus was higher in the MFC than in the LFC, but permeability did not change. We have developed a method that can measure natural alterations in cartilage material properties in a murine joint, which will be useful in identifying changes in cartilage mechanics with degeneration, pathology, or treatment.

Longitudinal Study of Human Hearings: Its Relationship to Noise and Other Factors. 1. Design of Five Year Study; Data from First Year

DTIC Science & Technology

1977-03-01

I i ,-, r .Lt-hc,uqh thei-e was little evidence of a . - - 4 n the frequency of interruptions ’p -f . articular ear (scores 2 and 3). ::Itr t r .he...boy’s increments are artifactual due to inattention, distraction , etc., during the second visit. His total noise scores (total period and interval) at

Curcumin inhibits pro-inflammatory mediators and metalloproteinase-3 production by chondrocytes.

PubMed

Mathy-Hartert, M; Jacquemond-Collet, I; Priem, F; Sanchez, C; Lambert, C; Henrotin, Y

2009-12-01

This study aims to investigate the effects of curcumin (Cur) on the extracellular matrix protein metabolism of articular chondrocytes and on their production of inflammatory mediators. Human chondrocytes in alginate beads and human cartilage explants were cultured in the absence or in the presence of interleukin (IL)-1beta (10(-11) M) and with or without Cur (5-20 microM). Nitric oxide (NO) synthesis was measured by the Griess spectrophotometric method; prostaglandin (PG) E(2) by a specific radioimmunoassay; and IL-6, IL-8, aggrecan (Agg), matrix metalloproteinase (MMP)-3, and tissue inhibitor of metalloproteinase (TIMP)-1 by specific enzyme-amplified immunoassays. Proteoglycan degradation was evaluated by the release of (35)S-glycosaminoglycans (GAG) from human cartilage explants. In alginate beads and cartilage explant models, Cur inhibited the basal and the IL-1beta-stimulated NO, PGE(2), IL-6, IL-8, and MMP-3 production by human chondrocytes in a concentration-dependent manner. The TIMP-1 and the Agg productions were not modified. In the basal condition, (35)S-GAG release from cartilage explants was decreased by Cur. Curcumin was a potent inhibitor of the production of inflammatory and catabolic mediators by chondrocytes, suggesting that this natural compound could be efficient in the treatment of osteoarthritis.

Light microscopic histology of supraspinatus tendon ruptures.

PubMed

Longo, Umile Giuseppe; Franceschi, Francesco; Ruzzini, Laura; Rabitti, Carla; Morini, Sergio; Maffulli, Nicola; Forriol, Francisco; Denaro, Vincenzo

2007-11-01

We analysed the morphological features of the human surgical specimens of supraspinatus tendon from patients with rotator cuff tears. Tendon samples were harvested from 31 subjects (21 men and 10 women; mean age 51 years, range 38-64) who underwent arthroscopic repair of a rotator cuff tear, and from five male patients who died of cardiovascular events (mean age, 69.6 years). Histological examination was performed using Haematoxylin and Eosin, Masson's Trichrome and Van Gieson's connective tissue stain. The specimens were examined twice by the same examiner under white light and polarized light microscopy. Particular effort was made to assess any evidence of the changes associated with tendinopathy. Within each specific category of tendon abnormalities, the chi-square test showed significant differences between the control and ruptured tendons (P < 0.05). Using the kappa statistics, the agreement between the two readings ranged from 0.57 to 0.84. We found thinning and disorientation of collagen fibres and chondroid metaplasia to be more pronounced on the articular side of the specimens from patients with rotator cuff tear (P < 0.05). The present study provides a description of the histological architecture of human surgical specimens of normal supraspinatus tendon from patients with rotator cuff tears and demonstrates more frequent tendon changes on the articular side of the rotator cuff.

Effects of tofacitinib on nucleic acid metabolism in human articular chondrocytes.

PubMed

Koizumi, Hideki; Arito, Mitsumi; Endo, Wataru; Kurokawa, Manae S; Okamoto, Kazuki; Omoteyama, Kazuki; Suematsu, Naoya; Beppu, Moroe; Kato, Tomohiro

2015-07-01

In our previous screening of chondrocyte protein profiles, the amount of adenosine monophosphate deaminase (AMPD) 2 was found to be decreased by tofacitinib. Extending the study, here we confirmed the decrease of AMPD2 by tofacitinib and further investigated effects of tofacitinib on purine nucleotide metabolism. Human articular chondrocytes and a chondrosarcoma cell line: OUMS-27 were stimulated with tofacitinib. Then the levels of AMPD2 and its related enzymes were investigated by Western blot. The levels of AMP and adenosine were assessed by mass spectrometry. We confirmed the significant decrease of AMPD2 by tofacitinib in chondrocytes (p = 0.025). The levels of adenosine kinase and 5'-nucleotidase were decreased in chondrocytes, although they did not meet statistical significance (p = 0.067 and p = 0.074, respectively). The results from OUMS-27 were similar to those from the chondrocytes. The cellular adenosine levels were significantly decreased by tofacitinib in OUMS-27 (p = 0.014). The cellular AMP levels were increased, although they did not meet statistical significance in OUMS-27 (p = 0.066). Our data indicate that tofacitinib increases the cellular levels of adenosine, which is known to have anti-inflammatory activity, through the downregulation of AMPD2. This would be a novel functional aspect of tofacitinib.

Actinomyces timonensis sp. nov., isolated from a human clinical osteo-articular sample.

PubMed

Renvoise, Aurélie; Raoult, Didier; Roux, Véronique

2010-07-01

Gram-positive, non-spore-forming rods were isolated from a human osteo-articular sample (strain 7400942(T)). Based on cellular morphology and the results of biochemical analysis, this strain was tentatively identified as a novel species of the genus Actinomyces. Phylogenetic analysis based on 16S rRNA gene sequence comparisons showed that the bacterium was closely related to the type strain of Actinomyces denticolens (96.9 % 16S rRNA gene sequence similarity). A comparison of biochemical traits showed that strain 7400942(T) was distinct from A. denticolens in a number of characteristics, i.e. in contrast with A. denticolens, strain 7400942(T) was negative for nitrate reduction and for beta-galactosidase, alpha-glucosidase and alanine arylamidase activities, it was positive for acid production from N-acetylglucosamine, melezitose and glycogen, and it was negative for acid production from turanose. Matrix-assisted laser-desorption/ionization time-of-flight MS protein analysis confirmed that strain 7400942(T) represents a novel species, as scores obtained for its spectra were significant (>2.2) only with strain 7400942(T). On the basis of phenotypic data and phylogenetic inference, it is proposed that this strain should be designated Actinomyces timonensis sp. nov.; the type strain is strain 7400942(T) (=CSUR P35(T)=CCUG 55928(T)).

Monomeric, porous type II collagen scaffolds promote chondrogenic differentiation of human bone marrow mesenchymal stem cells in vitro

NASA Astrophysics Data System (ADS)

Tamaddon, M.; Burrows, M.; Ferreira, S. A.; Dazzi, F.; Apperley, J. F.; Bradshaw, A.; Brand, D. D.; Czernuszka, J.; Gentleman, E.

2017-03-01

Osteoarthritis (OA) is a common cause of pain and disability and is often associated with the degeneration of articular cartilage. Lesions to the articular surface, which are thought to progress to OA, have the potential to be repaired using tissue engineering strategies; however, it remains challenging to instruct cell differentiation within a scaffold to produce tissue with appropriate structural, chemical and mechanical properties. We aimed to address this by driving progenitor cells to adopt a chondrogenic phenotype through the tailoring of scaffold composition and physical properties. Monomeric type-I and type-II collagen scaffolds, which avoid potential immunogenicity associated with fibrillar collagens, were fabricated with and without chondroitin sulfate (CS) and their ability to stimulate the chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells was assessed. Immunohistochemical analyses showed that cells produced abundant collagen type-II on type-II scaffolds and collagen type-I on type-I scaffolds. Gene expression analyses indicated that the addition of CS - which was released from scaffolds quickly - significantly upregulated expression of type II collagen, compared to type-I and pure type-II scaffolds. We conclude that collagen type-II and CS can be used to promote a more chondrogenic phenotype in the absence of growth factors, potentially providing an eventual therapy to prevent OA.

The synovial microenvironment of osteoarthritic joints alters RNA-seq expression profiles of human primary articular chondrocytes

PubMed Central

Lewallen, Eric A.; Bonin, Carolina A.; Li, Xin; Smith, Jay; Karperien, Marcel; Larson, A. Noelle; Lewallen, David G.; Cool, Simon M.; Westendorf, Jennifer J.; Krych, Aaron J.; Leontovich, Alexey A.; Im, Hee-Jeong; van Wijnen, Andre J.

2018-01-01

Osteoarthritis (OA) is a disabling degenerative joint disease that prompts pain with limited treatment options. To permit early diagnosis and treatment of OA, a high resolution mechanistic understanding of human chondrocytes in normal and diseased states is necessary. In this study, we assessed the biological effects of OA-related changes in the synovial microenvironment on chondrocytes embedded within anatomically intact cartilage from joints with different pathological grades by next generation RNA-sequencing (RNA-seq). We determined the transcriptome of primary articular chondrocytes derived from pristine knees and ankles, as well as from joints affected by OA. The GALAXY bioinformatics platform was used to facilitate biological interpretations. Comparisons of patient samples by k-means, hierarchical clustering and principal component analysis reveal that primary chondrocytes exhibit OA grade-related differences in gene expression, including genes involved in cell-adhesion, ECM production and immune response. We conclude that diseased synovial microenvironments in joints with different histopathological OA grades directly alter gene expression in chondrocytes. One ramification of this finding is that sampling anatomically intact cartilage from OA joints is not an ideal source of healthy chondrocytes, nor should they be used to generate a normal baseline for the molecular characterization of diseased joints. PMID:27378743

Polar extract of Curcuma longa protects cartilage homeostasis: possible mechanism of action.

PubMed

Velusami, Chandrasekaran Chinampudur; Richard, Edwin Jothie; Bethapudi, Bharathi

2018-01-08

Curcuma longa has been well documented for managing joint inflammation and pain. The present study investigated the effect of polar extract of C. longa (NR-INF-02) on cartilage homeostasis in human articular chondrocytes knee (NHAC-kn) cells to understand its plausible mechanism of action. Dysregulation of cartilage homeostasis was induced by IL-1β and H 2 O 2 . Modulating effects of NR-INF-02 on degradation markers viz., chondrocyte apoptosis, senescence, cytokine, eicosanoids, and cartilage synthesis markers viz., glycosaminoglycans and type II collagen degradation was evaluated in human articular chondrocytes knee (NHAC-kn) cells. Further, the effect of NR-INF-02 on lipopolysaccharide (LPS)-induced expression of NF-kB in RAW264.7 macrophages was investigated. NR-INF-02 significantly attenuated IL-1β-induced chondrocyte cytotoxicity, apoptosis and release of chondrocyte degradation markers such as IL-6, IL-8, COX-2, PGE 2 , TNF-α, ICAM-1 in NHAC-kn cells. Also, NR-INF-02 protected IL-1β-induced damage to synthesis markers such as glycosaminoglycans, type II collagen and further attenuated H 2 O 2 -induced chondrocyte senescence. In addition NR-INF-02 suppressed LPS-induced NF-kB expression in RAW264.7 cells. NR-INF-02 protects cartilage homeostasis by maintaining the balance between synthesis and degradation of cartilage matrix.

Growth factor transgenes interactively regulate articular chondrocytes.

PubMed

Shi, Shuiliang; Mercer, Scott; Eckert, George J; Trippel, Stephen B

2013-04-01

Adult articular chondrocytes lack an effective repair response to correct damage from injury or osteoarthritis. Polypeptide growth factors that stimulate articular chondrocyte proliferation and cartilage matrix synthesis may augment this response. Gene transfer is a promising approach to delivering such factors. Multiple growth factor genes regulate these cell functions, but multiple growth factor gene transfer remains unexplored. We tested the hypothesis that multiple growth factor gene transfer selectively modulates articular chondrocyte proliferation and matrix synthesis. We tested the hypothesis by delivering combinations of the transgenes encoding insulin-like growth factor I (IGF-I), fibroblast growth factor-2 (FGF-2), transforming growth factor beta1 (TGF-β1), bone morphogenetic protein-2 (BMP-2), and bone morphogenetic protien-7 (BMP-7) to articular chondrocytes and measured changes in the production of DNA, glycosaminoglycan, and collagen. The transgenes differentially regulated all these chondrocyte activities. In concert, the transgenes interacted to generate widely divergent responses from the cells. These interactions ranged from inhibitory to synergistic. The transgene pair encoding IGF-I and FGF-2 maximized cell proliferation. The three-transgene group encoding IGF-I, BMP-2, and BMP-7 maximized matrix production and also optimized the balance between cell proliferation and matrix production. These data demonstrate an approach to articular chondrocyte regulation that may be tailored to stimulate specific cell functions, and suggest that certain growth factor gene combinations have potential value for cell-based articular cartilage repair. Copyright © 2012 Wiley Periodicals, Inc.

Correlation between radiographic findings of osteoarthritis and arthroscopic findings of articular cartilage degeneration within the patellofemoral joint.

PubMed

Kijowski, Richard; Blankenbaker, Donna; Stanton, Paul; Fine, Jason; De Smet, Arthur

2006-12-01

To correlate radiographic findings of osteoarthritis on axial knee radiographs with arthroscopic findings of articular cartilage degeneration within the patellofemoral joint in patients with chronic knee pain. The study group consisted of 104 patients with osteoarthritis of the patellofemoral joint and 30 patients of similar age with no osteoarthritis of the patellofemoral joint. All patients in the study group had an axial radiograph of the knee performed prior to arthroscopic knee surgery. At the time of arthroscopy, each articular surface of the patellofemoral joint was graded using the Noyes classification system. Two radiologists retrospectively reviewed the knee radiographs to determine the presence of marginal osteophytes, joint-space narrowing, subchondral sclerosis, and subchondral cysts. The sensitivity and specificity of the various radiographic features of osteoarthritis for the detection of articular cartilage degeneration within the patellofemoral joint were determined. The sensitivity of marginal osteophytes, joint-space narrowing, subchondral sclerosis, and subchondral cysts for the detection of articular cartilage degeneration within the patellofemoral joint was 73%, 37%, 4%, and 0% respectively. The specificity of marginal osteophytes, joint-space narrowing, subchondral sclerosis, and subchondral cysts for the detection of articular cartilage degeneration within the patellofemoral joint was 67%, 90%, 100%, and 100% respectively. Marginal osteophytes were the most sensitive radiographic feature for the detection of articular cartilage degeneration within the patellofemoral joint. Joint-space narrowing, subchondral sclerosis, and subchondral cysts were insensitive radiographic features of osteoarthritis, and rarely occurred in the absence of associated osteophyte formation.

Non-destructive electromechanical assessment (Arthro-BST) of human articular cartilage correlates with histological scores and biomechanical properties.

PubMed

Sim, S; Chevrier, A; Garon, M; Quenneville, E; Yaroshinsky, A; Hoemann, C D; Buschmann, M D

2014-11-01

The hand-held Arthro-BST™ device is used to map electromechanical properties of articular cartilage. The purpose of the study was to evaluate correlation of electromechanical properties with histological, biochemical and biomechanical properties of cartilage. Electromechanical properties (quantitative parameter (QP)) of eight human distal femurs were mapped manually ex vivo using the Arthro-BST (1 measure/site, 5 s/measure, 3209 sites). Osteochondral cores were then harvested from different areas on the femurs and assessed with the Mankin histological score. Prior to histoprocessing, cores were tested in unconfined compression. A subset of the cores was analyzed with polarized light microscopy (PLM) to assess collagen structure. Biochemical assays were done on additional cores to obtain water content and glycosaminoglycan (GAG) content. The QP corresponding to each core was calculated by averaging all QPs collected within 6 mm of the core center. The electromechanical QP correlated strongly with both the Mankin score and the PLM score (r = 0.73, P < 0.0001 and r = -0.70, P < 0.0001 respectively) thus accurately reflecting tissue quality and collagen architecture. Electromechanical QP also correlated strongly with biomechanical properties including fibril modulus (r = -0.76, P < 0.0001), matrix modulus (r = -0.69, P < 0.0001), and log of permeability (r = 0.72, P < 0.0001). The QP correlated weakly with GAG per wet weight and with water content (r = -0.50, P < 0.0003 and r = 0.39, P < 0.006 respectively). Non-destructive electromechanical QP measurements correlate strongly with histological scores and biomechanical parameters providing a rapid and reliable assessment of articular cartilage quality. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Neutral solute transport across osteochondral interface: A finite element approach.

PubMed

Arbabi, Vahid; Pouran, Behdad; Weinans, Harrie; Zadpoor, Amir A

2016-12-08

Investigation of the solute transfer across articular cartilage and subchondral bone plate could nurture the understanding of the mechanisms of osteoarthritis (OA) progression. In the current study, we approached the transport of neutral solutes in human (slight OA) and equine (healthy) samples using both computed tomography and biphasic-solute finite element modeling. We developed a multi-zone biphasic-solute finite element model (FEM) accounting for the inhomogeneity of articular cartilage (superficial, middle and deep zones) and subchondral bone plate. Fitting the FEM model to the concentration-time curves of the cartilage and the equilibrium concentration of the subchondral plate/calcified cartilage enabled determination of the diffusion coefficients in the superficial, middle and deep zones of cartilage and subchondral plate. We found slightly higher diffusion coefficients for all zones in the human samples as compared to the equine samples. Generally the diffusion coefficient in the superficial zone of human samples was about 3-fold higher than the middle zone, the diffusion coefficient of the middle zone was 1.5-fold higher than that of the deep zone, and the diffusion coefficient of the deep zone was 1.5-fold higher than that of the subchondral plate/calcified cartilage. Those ratios for equine samples were 9, 2 and 1.5, respectively. Regardless of the species considered, there is a gradual decrease of the diffusion coefficient as one approaches the subchondral plate, whereas the rate of decrease is dependent on the type of species. Copyright © 2016 Elsevier Ltd. All rights reserved.

Total knee replacement with natural rollback.

PubMed

Wachowski, Martin Michael; Walde, Tim Alexander; Balcarek, Peter; Schüttrumpf, Jan Philipp; Frosch, Stephan; Stauffenberg, Caspar; Frosch, Karl-Heinz; Fiedler, Christoph; Fanghänel, Jochen; Kubein-Meesenburg, Dietmar; Nägerl, Hans

2012-03-20

A novel class of total knee replacement (AEQUOS G1) is introduced which features a unique design of the articular surfaces. Based on the anatomy of the human knee and differing from all other prostheses, the lateral tibial "plateau" is convexly curved and the lateral femoral condyle is posteriorly shifted in relation to the medial femoral condyle. Under compressive forces the configuration of the articular surfaces of human knees constrains the relative motion of femur and tibia in flexion/extension. This constrained motion is equivalent to that of a four-bar linkage, the virtual 4 pivots of which are given by the centres of curvature of the articulating surfaces. The dimensions of the four-bar linkage were optimized to the effect that constrained motion of the total knee replacement (TKR) follows the flexional motion of the human knee in close approximation, particularly during gait. In pilot studies lateral X-ray pictures have demonstrated that AEQUOS G1 can feature the natural rollback in vivo. Rollback relieves the load of the patello-femoral joint and minimizes retropatellar pressure. This mechanism should reduce the prevalence of anterior knee pain. The articulating surfaces roll predominantly in the stance phase. Consequently sliding friction is replaced by the lesser rolling friction under load. Producing rollback should minimize material wear due to friction and maximize the lifetime of the prosthesis. To definitely confirm these theses one has to wait for the long term results. Copyright © 2011 Elsevier GmbH. All rights reserved.

Changes in Mechanics and Composition of Human Talar Cartilage Anlagen During Fetal Development

PubMed Central

Mahmoodian, Roza; Leasure, Jeremi; Philip, Phitha; Pleshko, Nancy; Capaldi, Franco; Siegler, Sorin

2011-01-01

Objective Fetal cartilage anlage provides a framework for endochondral ossification and organization into articular cartilage. We previously reported differences between mechanical properties of talar cartilage anlagen and adult articular cartilage. However, the underlying development-associated changes remain to be established. Delineation of the normal evolvement of mechanical properties and its associated compositional basis provides insight into the natural mechanisms of cartilage maturation. Our goal was to address this issue. Materials and methods Human fetal cartilage anlagen were harvested from the tali of normal stillborn fetuses from 20 to 36 weeks of gestational age. Data obtained from stress relaxation experiments conducted under confined and unconfined compression configurations were processed to derive the compressive mechanical properties. The compressive mechanical properties were extracted from a linear fit to the equilibrium response in unconfined compression, and by using the nonlinear biphasic theory to fit to the experimental data from the confined compression experiment, both in stress-relaxation. The molecular composition was obtained using FTIR, and spatial maps of tissue contents per dry weight were created using FTIR imaging. Correlative and regression analyses were performed to identify relationships between the mechanical properties and age, compositional properties and age, and mechanical versus compositional parameters. Results All of the compositional quantities and the mechanical properties excluding the Poisson’s ratio changed with maturation. Stiffness increased by a factor of ~2.5 and permeability decreased by 20% over the period studied. Collagen content and degree of collagen integrity increased with age by ~3-fold, while the proteoglycan content decreased by 18%. Significant relations were found between the mechanical and compositional properties. Conclusion The mechanics of fetal talar cartilage is related to its composition, where the collagen and proteoglycan network play a prominent role. An understanding of the mechanisms of early cartilage maturation could provide a framework to guide tissue-engineering strategies. PMID:21843650

Hamster and Murine Models of Severe Destructive Lyme Arthritis

PubMed Central

Munson, Erik; Nardelli, Dean T.; Du Chateau, Brian K.; Callister, Steven M.; Schell, Ronald F.

2012-01-01

Arthritis is a frequent complication of infection in humans with Borrelia burgdorferi. Weeks to months following the onset of Lyme borreliosis, a histopathological reaction characteristic of synovitis including bone, joint, muscle, or tendon pain may occur. A subpopulation of patients may progress to a chronic, debilitating arthritis months to years after infection which has been classified as severe destructive Lyme arthritis. This arthritis involves focal bone erosion and destruction of articular cartilage. Hamsters and mice are animal models that have been utilized to study articular manifestations of Lyme borreliosis. Infection of immunocompetent LSH hamsters or C3H mice results in a transient synovitis. However, severe destructive Lyme arthritis can be induced by infecting irradiated hamsters or mice and immunocompetent Borrelia-vaccinated hamsters, mice, and interferon-gamma- (IFN-γ-) deficient mice with viable B. burgdorferi. The hamster model of severe destructive Lyme arthritis facilitates easy assessment of Lyme borreliosis vaccine preparations for deleterious effects while murine models of severe destructive Lyme arthritis allow for investigation of mechanisms of immunopathology. PMID:22461836

Tissue-engineered cartilage with inducible and tunable immunomodulatory properties

PubMed Central

Glass, Katherine A.; Link, Jarrett M.; Brunger, Jonathan M.; Moutos, Franklin T.; Gersbach, Charles A.; Guilak, Farshid

2014-01-01

The pathogenesis of osteoarthritis is mediated in part by inflammatory cytokines including interleukin-1 (IL-1), which promote degradation of articular cartilage and prevent human mesenchymal stem cell (MSC) chondrogenesis. In this study, we combined gene therapy and functional tissue engineering to develop engineered cartilage with immunomodulatory properties that allow chondrogenesis in the presence of pathologic levels of IL-1 by inducing overexpression of IL-1 receptor antagonist (IL-1Ra) in MSCs via scaffold-mediated lentiviral gene delivery. A doxycycline-inducible vector was used to transduce MSCs in monolayer or within 3D woven PCL scaffolds to enable tunable IL-1Ra production. In the presence of IL-1, IL-1Ra-expressing engineered cartilage produced cartilage-specific extracellular matrix, while resisting IL-1-induced upregulation of matrix metalloproteinases and maintaining mechanical properties similar to native articular cartilage. The ability of functional engineered cartilage to deliver tunable anti-inflammatory cytokines to the joint may enhance the long-term success of therapies for cartilage injuries or osteoarthritis. PMID:24767790

Articular Cartilage Repair Through Muscle Cell-Based Tissue Engineering

DTIC Science & Technology

2011-03-01

defects display good cell survival and can differentiate into chondrocytes that improve the healing of articular cartilage. We also have observed that... self -renewal to their regenerative capacity after transplantation into the cartilage defects (Technical Objective #1). Next, we will determine the...osteochondral defects display good cell survival and can differentiate into chondrocytes that improve the healing of articular cartilage. We also have

Articular congruity is associated with short-term clinical outcomes of operatively treated SER IV ankle fractures.

PubMed

Berkes, Marschall B; Little, Milton T M; Lazaro, Lionel E; Pardee, Nadine C; Schottel, Patrick C; Helfet, David L; Lorich, Dean G

2013-10-02

With regard to supination-external rotation type-IV (SER IV) ankle fractures, there is no consensus regarding which patient, injury, and treatment variables most strongly influence clinical outcome. The purpose of this investigation was to examine the impact of articular surface congruity on the functional outcomes of operatively treatment of SER IV ankle fractures. A prospectively generated database consisting of operatively treated SER IV ankle fractures was reviewed. Postoperative computed tomography (CT) scans were used to assess ankle joint congruity. Ankles were considered incongruent in the presence of >2 mm of articular step-off, intra-articular loose bodies, or an articular surface gap of >2 mm (despite an otherwise anatomic reduction) due to joint impaction and comminution. Patients with at least one year of clinical follow-up were eligible for analysis. The primary and secondary outcome measures were the Foot and Ankle Outcome Score (FAOS) and ankle motion. One hundred and eight SER IV fractures met our inclusion criteria. The average duration of follow-up was twenty-one months. Seventy-two patients (67%) had a congruent ankle joint, and thirty-six (33%) had elements of articular surface incongruity on postoperative CT scanning. These two groups were similar with regard to comorbidities and injury and treatment variables. At the time of the final follow-up, the group with articular incongruity had a significantly worse FAOS with regard to symptoms (p = 0.012), pain (p = 0.004), and activities of daily living (p = 0.038). Those with articular incongruity had worse average scores in the FAOS sport domain as well. No significant differences in ankle motion were found between the two groups. In this population of patients with an operatively treated SER IV ankle fracture, the presence of postoperative articular incongruity correlated with inferior early clinical outcomes. Orthopaedic surgeons should scrutinize ankle fracture reductions and strive for perfection to allow for the best possible clinical outcome. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Quantitative MRI T2 relaxation time evaluation of knee cartilage: comparison of meniscus-intact and -injured knees after anterior cruciate ligament reconstruction.

PubMed

Li, Hong; Chen, Shuang; Tao, Hongyue; Chen, Shiyi

2015-04-01

Associated meniscal injury is well recognized at anterior cruciate ligament (ACL) reconstruction, and it is a known risk factor for osteoarthritis. To evaluate and characterize the postoperative appearance of articular cartilage after different meniscal treatment in ACL-reconstructed knees using T2 relaxation time evaluation on MRI. Cohort study; Level of evidence, 3. A total of 62 consecutive patients who under ACL reconstruction were recruited in this study, including 23 patients undergoing partial meniscectomy (MS group), 21 patients undergoing meniscal repair (MR group), and 18 patients with intact menisci (MI group) at time of surgery. Clinical evaluation, including subjective functional scores and physical examination, was performed on the same day as the MRI examination and at follow-up times ranging from 2 to 4.2 years. The MRI multiecho sagittal images were segmented to determine the T2 relaxation time value of each meniscus and articular cartilage plate. Differences in each measurement were compared among groups. No patient had joint-line tenderness or reported pain or clicking on McMurray test or instability. There were also no statistically significant differences in functional scores or medial or lateral meniscus T2 values among the 3 groups (P > .05 for both). There was a significantly higher articular cartilage T2 value in the medial femorotibial articular cartilage for the MS group (P < .01) and the MR group (P < .05) compared with that of the MI group, while there was no significant difference in articular cartilage T2 value between the MS and MR groups (P > .05) in each articular cartilage plate. The medial tibial articular cartilage T2 value had a significant positive correlation with medial meniscus T2 value (r = 0.287; P = .024) CONCLUSION: This study demonstrates that knees with meniscectomy or meniscal repair had articular cartilage degeneration at 2 to 4 years postoperatively, with higher articular cartilage T2 relaxation time values compared with the knees with an intact meniscus. © 2015 The Author(s).

CCN Family Member 2/Connective Tissue Growth Factor (CCN2/CTGF) Has Anti-Aging Effects That Protect Articular Cartilage from Age-Related Degenerative Changes

PubMed Central

Itoh, Shinsuke; Hattori, Takako; Tomita, Nao; Aoyama, Eriko; Yutani, Yasutaka; Yamashiro, Takashi; Takigawa, Masaharu

2013-01-01

To examine the role of connective tissue growth factor CCN2/CTGF (CCN2) in the maintenance of the articular cartilaginous phenotype, we analyzed knee joints from aging transgenic mice (TG) overexpressing CCN2 driven by the Col2a1 promoter. Knee joints from 3-, 14-, 40-, and 60-day-old and 5-, 12-, 18-, 21-, and 24-month-old littermates were analyzed. Ccn2-LacZ transgene expression in articular cartilage was followed by X-gal staining until 5 months of age. Overexpression of CCN2 protein was confirmed through all ages in TG articular cartilage and in growth plates. Radiographic analysis of knee joints showed a narrowing joint space and other features of osteoarthritis in 50% of WT, but not in any of the TG mice. Transgenic articular cartilage showed enhanced toluidine blue and safranin-O staining as well as chondrocyte proliferation but reduced staining for type X and I collagen and MMP-13 as compared with those parameters for WT cartilage. Staining for aggrecan neoepitope, a marker of aggrecan degradation in WT articular cartilage, increased at 5 and 12 months, but disappeared at 24 months due to loss of cartilage; whereas it was reduced in TG articular cartilage after 12 months. Expression of cartilage genes and MMPs under cyclic tension stress (CTS) was measured by using primary cultures of chondrocytes obtained from wild-type (WT) rib cartilage and TG or WT epiphyseal cartilage. CTS applied to primary cultures of mock-transfected rib chondrocytes from WT cartilage and WT epiphyseal cartilage induced expression of Col1a1, ColXa1, Mmp-13, and Mmp-9 mRNAs; however, their levels were not affected in CCN2-overexpressing chondrocytes and TG epiphyseal cartilage. In conclusion, cartilage-specific overexpression of CCN2 during the developmental and growth periods reduced age-related changes in articular cartilage. Thus CCN2 may play a role as an anti-aging factor by stabilizing articular cartilage. PMID:23951098

[Patellar instability : diagnosis and treatment].

PubMed

Ngo, Trieu Hoai Nam; Martin, Robin

2017-12-13

The aim of this paper is to present recent advances in surgical management of patellar instability. Several anatomical factors were reported to promote instability. We propose to classify them in two groups. Extra articular factors are valgus and torsion deformity. Articular factors include trochlea and patella dysplasia, tibial tubercle lateralization and medial patellofemoral ligament (MPFL) insufficiency. Acute patellar dislocations are treated conservatively, with exception for osteochondral and MPFL avulsion fractures that require acute reinsertion. Surgery is considered for recurrent instability. As we aim for a correction of all contributing elements, we prefer a two stages approach. Extra articular factors are treated first by osteotomy, followed by articular factors after 4-6 months. This allows separate rehabilitation protocols.

Transcription factor ERG and joint and articular cartilage formation during mouse limb and spine skeletogenesis.

PubMed

Iwamoto, Masahiro; Tamamura, Yoshihiro; Koyama, Eiki; Komori, Toshihisa; Takeshita, Nobuo; Williams, Julie A; Nakamura, Takashi; Enomoto-Iwamoto, Motomi; Pacifici, Maurizio

2007-05-01

Articular cartilage and synovial joints are critical for skeletal function, but the mechanisms regulating their development are largely unknown. In previous studies we found that the ets transcription factor ERG and its alternatively-spliced variant C-1-1 have roles in joint formation in chick. Here, we extended our studies to mouse. We found that ERG is also expressed in developing mouse limb joints. To test regulation of ERG expression, beads coated with the joint master regulator protein GDF-5 were implanted close to incipient joints in mouse limb explants; this led to rapid and strong ectopic ERG expression. We cloned and characterized several mammalian ERG variants and expressed a human C-1-1 counterpart (hERG3Delta81) throughout the cartilaginous skeleton of transgenic mice, using Col2a1 gene promoter/enhancer sequences. The skeletal phenotype was severe and neonatal lethal, and the transgenic mice were smaller than wild type littermates and their skeletons were largely cartilaginous. Limb long bone anlagen were entirely composed of chondrocytes actively expressing collagen IX and aggrecan as well as articular markers such as tenascin-C. Typical growth plates were absent and there was very low expression of maturation and hypertrophy markers, including Indian hedgehog, collagen X and MMP-13. The results suggest that ERG is part of molecular mechanisms leading chondrocytes into a permanent developmental path and become joint forming cells, and may do so by acting downstream of GDF-5.

SEWER AND TANK FLUSHING FOR CORROSION AND POLLUTION CONTROL

EPA Science Inventory

This paper presents an overview of the causes of sewer deterioration and control methods that can prevent or arrest this deterioration. articular, the paper addresses the use of inline- and combined sewer overflow (CSO) storage tank-flushing systems for removing sediments and mi...

Magnetic resonance imaging of articular cartilage: trauma, degeneration, and repair.

PubMed

Potter, Hollis G; Foo, Li F

2006-04-01

The assessment of articular cartilage using magnetic resonance imaging has seen considerable advances in recent years. Cartilage morphologic characteristics can now be evaluated with a high degree of accuracy and reproducibility using dedicated pulse sequences, which are becoming standard at many institutions. These techniques detect clinically unsuspected traumatic cartilage lesions, allowing the physician to study their natural history with longitudinal evaluation and also to assess disease status in degenerative osteoarthritis. Magnetic resonance imaging also provides a more objective assessment of cartilage repair to augment the information obtained from more subjective clinical outcome instruments. Newly developed methods that provide detail at an ultrastructural level offer an important addition to cartilage evaluation, particularly in the detection of early alterations in the extracellular matrix. These methods have created an undeniably important role for magnetic resonance imaging in the reproducible, noninvasive, and objective evaluation and monitoring of cartilage. An overview of the advances, current techniques, and impact of magnetic resonance imaging in the setting of trauma, degenerative arthritides, and surgical treatment for cartilage injury is presented.

Anti-nociceptive effect of thalidomide on zymosan-induced experimental articular incapacitation.

PubMed

Vale, Mariana L; Cunha, Fernando Q; Brito, Gerly A C; Benevides, Verônica M; Ferreira, Sérgio H; Poole, Stephen; Ribeiro, Ronaldo A

2006-05-01

The anti-nociceptive effect of thalidomide on zymosan-induced articular knee joint incapacitation in rats was investigated. Thalidomide (5-45 mg/kg), given 30 min before but not 2 h after the intra-articular injection of zymosan, inhibited the nociceptive response in a dose-dependent manner. Furthermore, thalidomide pretreatment significantly reduced the concentration of tumor necrosis factor-alpha (TNF-alpha, -68.4%) in the exudate of zymosan-injected joints, but not those of interleukin-1beta, interleukin-6, CINC-1 or interleukin-10. The expression of TNF-alpha, determined by immunohistochemical staining, in synovial tissues obtained from articular joints injected with zymosan was also inhibited by thalidomide pretreatment. The anti-nociceptive effect of thalidomide was not reversed by the co-administration of an opioid receptor antagonist, naloxone, suggesting that endogenous opioids do not mediate the anti-nociceptive effect of thalidomide in this model. In conclusion, the anti-nociceptive activity of thalidomide in zymosan-induced articular incapacitation is associated with the inhibition of TNF-alpha by resident synovial cells.

MRI of articular cartilage at microscopic resolution

PubMed Central

Xia, Y.

2013-01-01

This review briefly summarises some of the definitive studies of articular cartilage by microscopic MRI (µMRI) that were conducted with the highest spatial resolutions. The article has four major sections. The first section introduces the cartilage tissue, MRI and µMRI, and the concept of image contrast in MRI. The second section describes the characteristic profiles of three relaxation times (T1, T2 and T1ρ) and self-diffusion in healthy articular cartilage. The third section discusses several factors that can influence the visualisation of articular cartilage and the detection of cartilage lesion by MRI and µMRI. These factors include image resolution, image analysis strategies, visualisation of the total tissue, topographical variations of the tissue properties, surface fibril ambiguity, deformation of the articular cartilage, and cartilage lesion. The final section justifies the values of multidisciplinary imaging that correlates MRI with other technical modalities, such as optical imaging. Rather than an exhaustive review to capture all activities in the literature, the studies cited in this review are merely illustrative. PMID:23610697

[Posttraumatic deformities of the knee joint : Intra-articular osteotomy after malreduction of tibial head fractures].

PubMed

Frosch, K-H; Krause, M; Frings, J; Drenck, T; Akoto, R; Müller, G; Madert, J

2016-10-01

Malreduction of tibial head fractures often leads to malalignment of the lower extremity, pain, limited range of motion and instability. The extent of the complaints and the degree of deformity requires an exact analysis and a standardized approach. True ligamentous instability should be distinguished from pseudoinstability of the joint. Also extra- and intra-articular deformities have to be differentiated. In intra-articular deformities the extent of articular surface displacement, defects and clefts must be accurately evaluated. A specific surgical approach is necessary, which allows adequate visualization, correct osteotomy and refixation of the fractured area of the tibial head. In the long-term course good clinical results are described for intra-articular osteotomies. If the joint is damaged to such an extent that it cannot be reconstructed or in cases of advanced posttraumatic osteoarthritis, total knee arthroplasty may be necessary; however, whenever possible and reasonable, anatomical reconstruction and preservation of the joint should be attempted.

Mesenchymal stem cells in cartilage regeneration.

PubMed

Savkovic, Vuk; Li, Hanluo; Seon, Jong-Keun; Hacker, Michael; Franz, Sandra; Simon, Jan-Christoph

2014-01-01

Articular cartilage provides life-long weight-bearing and mechanical lubrication with extraordinary biomechanical performance and simple structure. However, articular cartilage is apparently vulnerable to multifactorial damage and insufficient to self-repair, isolated in articular capsule without nerves or blood vessels. Osteoarthritis (OA) is known as a degenerative articular cartilage deficiency progressively affecting large proportion of the world population, and restoration of hyaline cartilage is clinical challenge to repair articular cartilage lesion and recreate normal functionality over long period. Mesenchymal stem cells (MSC) are highly proliferative and multipotent somatic cells that are able to differentiate mesoderm-derived cells including chondrocytes and osteoblasts. Continuous endeavors in basic research and preclinical trial have achieved promising outcomes in cartilage regeneration using MSCs. This review focuses on rationale and technologies of MSC-based hyaline cartilage repair involving tissue engineering, 3D biomaterials and growth factors. By comparing conventional treatment and current research progress, we describe insights of advantage and challenge in translation and application of MSC-based chondrogenesis for OA treatment.

Variation of mechanical property of single-walled carbon nanotubes-treated cells explored by atomic force microscopy.

PubMed

Dulińska-Molak, Ida; Mao, Hongli; Kawazoe, Naoki; Chen, Guoping

2014-04-01

With a range of biological properties, single-walled carbon nanotubes (SWCNTs) are a promising material for nanobiotechnology. Concerns about their potential effect on human health have led to the interest in understanding the interaction between SWCNTs and cells. There are many reports showing the potential cellular effects of SWCNTs but this issue is quite controversially discussed in the literature. In this study, we used conventional biological evaluation methods and atomic force microscopy (AFM) to compare the effects of SWCNTs on three different cell types: bovine articular chondrocytes, human bone marrow-derived mesenchymal stem cells and HeLa cells. No obvious effects of SWCNTs on cell morphology and viability were observed during 3 days in vitro culture. However, SWCNTs significantly increased the Young's modulus of all the three types of cells. The effect of SWCNTs on Young's modulus was in an increasing order of Hela cells < chondrocytes < mesenchymal stem cells. AFM was shown to be a useful tool for investigation of the effect of nanomaterials on mechanical property of cells.

Intra-Articular Therapeutic Delivery for Post Traumatic Osteoarthritis

DTIC Science & Technology

2015-10-01

AWARD NUMBER: W81XWH-14-2-0188 TITLE: Intra-Articular Therapeutic Delivery for Post-Traumatic Osteoarthritis PRINCIPAL INVESTIGATOR: Robert...Intra-Articular Therapeutic Delivery for Post-Traumatic Osteoarthritis 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-2-0188 5c. PROGRAM ELEMENT...are to test the ability of a novel therapeutic to hinder the progression of post-traumatic osteoarthritis . This debilitating joint condition more

Effects of immobilization on articular cartilage: Autohistoradiographic findings with S35

NASA Technical Reports Server (NTRS)

Digiovanni, C.; Desantis, E.

1980-01-01

The effect of immobilization on the articular cartilage of rabbits was studied by light microscope. The knee joint of each rabbit was immobilized in a plaster in a position midway between flexion and extension for a 10 to 120 days period. Degenerative changes in the articular cartilage of increasing severity were observed. The fixation of the labeled SO4 by cartilage cells was decreased in advanced immobilization.

New Frontiers for Cartilage Repair and Protection.

PubMed

Zaslav, Kenneth; McAdams, Timothy; Scopp, Jason; Theosadakis, Jason; Mahajan, Vivek; Gobbi, Alberto

2012-01-01

Articular cartilage injury is common after athletic injury and remains a difficult treatment conundrum both for the surgeon and athlete. Although recent treatments for damage to articular cartilage have been successful in alleviating symptoms, more durable and complete, long-term articular surface restoration remains the unattained goal. In this article, we look at both new ways to prevent damage to articular surfaces as well as new techniques to recreate biomechanically sound and biochemically true articular surfaces once an athlete injures this surface. This goal should include reproducing hyaline cartilage with a well-integrated and flexible subchondral base and the normal zonal variability in the articular matrix. A number of nonoperative interventions have shown early promise in mitigating cartilage symptoms and in preclinical studies have shown evidence of chondroprotection. These include the use of glucosamine, chondroitin, and other neutraceuticals, viscosupplementation with hyaluronic acid, platelet-rich plasma, and pulsed electromagnetic fields. Newer surgical techniques, some already in clinical study, and others on the horizon offer opportunities to improve the surgical restoration of the hyaline matrix often disrupted in athletic injury. These include new scaffolds, single-stage cell techniques, the use of mesenchymal stem cells, and gene therapy. Although many of these treatments are in the preclinical and early clinical study phase, they offer the promise of better options to mitigate the sequelae of athletically induced cartilage.

The effects of intermittent hydrostatic pressure on self-assembled articular cartilage constructs.

PubMed

Hu, Jerry C; Athanasiou, Kyriacos A

2006-05-01

To date, static culture for the tissue engineering of articular cartilage has shown to be inadequate in conferring functionality to constructs. Various forms of mechanical stimuli accompany articular cartilage development in vivo, and one of these is hydrostatic pressure. This study used histology, biochemistry, and biomechanics to examine the effects of intermittent hydrostatic pressure, applied at 10 MPa and 1 Hz for 4 h per day for 5 days per week for up to 8 weeks on self-assembled chondrocyte constructs. The self-assembling process is a novel approach that allows engineering of articular cartilage constructs without the use of exogenous scaffolds. The self-assembled constructs were found to be capable of enduring this loading regimen. Significant increases in collagen production were only observed in pressurized samples. Intermittent hydrostatic pressure prevented a significant decrease in total GAG, which was significant in controls. Aside from the beneficial effects intermittent hydrostatic pressure may have on ECM synthesis, its effects on mechanical properties may require longer culture periods to manifest. This study demonstrates the successful use of the self-assembling process to produce articular cartilage constructs. It also shows for the first time that long-term culture of tissue-engineered articular cartilage construct benefits from intermittent hydrostatic pressure.

Indentation stiffness does not discriminate between normal and degraded articular cartilage.

PubMed

Brown, Cameron P; Crawford, Ross W; Oloyede, Adekunle

2007-08-01

Relative indentation characteristics are commonly used for distinguishing between normal healthy and degraded cartilage. The application of this parameter in surgical decision making and an appreciation of articular cartilage biomechanics has prompted us to hypothesise that it is difficult to define a reference stiffness to characterise normal articular cartilage. This hypothesis is tested for validity by carrying out biomechanical indentation of articular cartilage samples that are characterised as visually normal and degraded relative to proteoglycan depletion and collagen disruption. Compressive loading was applied at known strain rates to visually normal, artificially degraded and naturally osteoarthritic articular cartilage and observing the trends of their stress-strain and stiffness characteristics. While our results demonstrated a 25% depreciation in the stiffness of individual samples after proteoglycan depletion, they also showed that when compared to the stiffness of normal samples only 17% lie outside the range of the stress-strain behaviour of normal samples. We conclude that the extent of the variability in the properties of normal samples, and the degree of overlap (81%) of the biomechanical properties of normal and degraded matrices demonstrate that indentation data cannot form an accurate basis for distinguishing normal from abnormal articular cartilage samples with consequences for the application of this mechanical process in the clinical environment.

Biomechanical analysis of the influence of friction in jaw joint disorders.

PubMed

Koolstra, J H

2012-01-01

Increased friction due to impaired lubrication in the jaw joint has been considered as one of the possible causes for internal joint disorders. A very common internal disorder in the jaw joint is an anteriorly dislocated articular disc. This is generally considered to contribute to the onset of arthritic injuries. Increase of friction as caused by impairment of lubrication is suspected to be a possible cause for such a disorder. The influence of friction was addressed by analysis of its effects on tensions and deformations of the cartilaginous structures in the jaw joint using computational biomechanical analysis. Jaw open-close movements were simulated while in one or two compartments of the right joint friction was applied in the articular contact. The left joint was treated as the healthy control. The simulations predicted that friction primarily causes increased shear stress in the articular cartilage layers, but hardly in the articular disc. This suggests that impaired lubrication may facilitate deterioration of the cartilage-subchondral bone unit of the articular surfaces. The results further suggest that increased friction is not a plausible cause for turning a normally functioning articular disc into an anteriorly dislocated one. Copyright © 2011 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

The control of mono-articular muscles in multijoint leg extensions in man.

PubMed Central

van Ingen Schenau, G J; Dorssers, W M; Welter, T G; Beelen, A; de Groot, G; Jacobs, R

1995-01-01

1. Movements often require control of direction and a magnitude of force exerted externally on the environment. Bi-articular upper leg muscles appear to play a unique role in the regulation of the net torques about the hip and knee joints, necessary for the control of this external force. 2. The aim of this study was to test the hypothesis that the mono-articular muscles act as work generators in powerful dynamic leg extensions, which means that they should be activated primarily in the phases during which they can contribute to work, irrespective of the net joint torques required to control the external force. 3. Cycling movements of six trained subjects were analysed by means of inverse dynamics, yielding net joint torques as well as activity patterns and shortening velocities of four mono- and four bi-articular leg muscles. 4. The results show that the mono-articular muscles exert force only in the phase in which these muscles shorten, whereas this appears not to be the case for the bi-articular muscles. 5. Reciprocal patterns of activation of the rectus femoris and hamstring muscles appear to tune the distribution of net joint torques about the hip and knee joints, necessary to control the (changing) direction of the force on the pedal. 6. An analysis of running in man and additional related literature based on animal studies appears to provide further support for the hypothesis that mono- and bi-articular muscles have essentially different roles in these powerful multijoint leg extension tasks. PMID:7602524

Polyethylene wear in Oxford unicompartmental knee replacement: a retrieval study of 47 bearings.

PubMed

Kendrick, B J L; Longino, D; Pandit, H; Svard, U; Gill, H S; Dodd, C A F; Murray, D W; Price, A J

2010-03-01

The Oxford Unicompartmental Knee replacement (UKR) was introduced as a design to reduce polyethylene wear. There has been one previous retrieval study involving this implant, which reported very low rates of wear in some specimens but abnormal patterns of wear in others. There has been no further investigation of these abnormal patterns. The bearings were retrieved from 47 patients who had received a medial Oxford UKR for anteromedial osteoarthritis of the knee. None had been studied previously. The mean time to revision was 8.4 years (sd 4.1), with 20 having been implanted for over ten years. The macroscopic pattern of polyethylene wear and the linear penetration were recorded for each bearing. The mean rate of linear penetration was 0.07 mm/year. The patterns of wear fell into three categories, each with a different rate of linear penetration; 1) no abnormal macroscopic wear and a normal articular surface, n = 16 (linear penetration rate = 0.01 mm/year); 2) abnormal macroscopic wear and normal articular surfaces with extra-articular impingement, n = 16 (linear penetration rate = 0.05 mm/year); 3) abnormal macroscopic wear and abnormal articular surfaces with intra-articular impingement +/- signs of non-congruous articulation, n = 15 (linear penetration rate = 0.12 mm/year). The differences in linear penetration rate were statistically significant (p < 0.001). These results show that very low rates of polyethylene wear are possible if the device functions normally. However, if the bearing displays suboptimal function (extra-articular, intra-articular impingement or incongruous articulation) the rates of wear increase significantly.

Articular disc and eminence modeling after experimental relocation of the glenoid fossa in growing rabbits.

PubMed

Pirttiniemi, P; Kantomaa, T; Tuominen, M; Salo, L

1994-02-01

The articular surface of the glenoid fossa shows some analogy to the mandibular condyle, since the surface is covered by secondary cartilage, which makes the process more elastic than purely bony structures. The condylar cartilage has been shown to be responsive to alterations in load pressures, and this secondary type of cartilage is also able to increase its proliferative activity to a limited extent when the load pressure is altered. The aim here was to measure changes in proliferative activity and type II collagen secretion in the articular surface of the glenoid fossa after steady experimental posterior relocation of the fossa in the rabbit without actively interfering with normal masticatory action. The shape of the articular disc and interrelations of the joint components were measured macroscopically. Twenty-four five-day-old rabbits underwent gluing of the interparietal, temporoparietal, and lambdoidal sutures. Three experimental and 3 control rabbits were injected with tritiated thymidine at 10, 15, 20, and 30 days and were killed after 2 h for histological, autoradiographic, and immunohistochemical examination. The total number of labeled cells in the proliferative layer near the articular eminence was higher in the experimental group, the difference being greatest in the 15- and 20-day-old rabbits. Immunohistochemical examination revealed less staining for type II collagen on the postero-inferior side of the eminence in the experimental group. The articular disc was flattened in the experimental group, and the elastic tissue bundle connecting the articular eminence and the anterior border of the disc was significantly narrower and longer.

The Articular Morphology of the First Carpometacarpal Joint Does Not Differ between Men and Women, but Changes with Aging and Early Stage Osteoarthritis

PubMed Central

Halilaj, Eni; Moore, Douglas C.; Laidlaw, David H.; Got, Christopher J.; Weiss, Arnold-Peter C.; Ladd, Amy L.; Crisco, Joseph J.

2014-01-01

The increased prevalence of thumb carpometacarpal (CMC) joint osteoarthritis (OA) in women has been previously linked to the articular morphology of the trapezium. However, studies report conflicting results on how the articular shapes of male and female trapezia compare to one another, mainly because their findings are based on data from older cadaver specimens. The purpose of this in vivo study was to dissociate the effect of sex from that of aging and early OA by using cohorts of healthy young and healthy older subjects, as well as patients with early stage OA. Computed tomography scans from 68 healthy subjects and 87 arthritic subjects were used to obtain 3-D bone models. The trapezial and metacarpal articular surfaces were manually delineated on scaled bone models, to remove the effect of size, and then were compared between sex, age, and health groups by using polar histograms of curvature and average curvature values. We found no sex differences, but significant age-group and health-group differences, in the articular surfaces of both bones. The older healthy subjects had higher curvature in the concave and lower curvature in the convex directions of both the trapezial and metacarpal saddles than the healthy young subjects. Subjects with early OA had significantly different metacarpal and trapezial articular shapes from healthy subjects. These findings suggest that aging and OA affect the articular shape of the CMC joint, but that, in contrast to previously held beliefs, inherent sex differences are not responsible for the higher incidence of CMC OA in women. PMID:24909332

Intra-Articular Blockade of P2X7 Receptor Reduces the Articular Hyperalgesia and Inflammation in the Knee Joint Synovitis Especially in Female Rats.

PubMed

Teixeira, Juliana Maia; Dias, Elayne Vieira; Parada, Carlos Amílcar; Tambeli, Cláudia Herrera

2017-02-01

Synovitis is a key factor in joint disease pathophysiology, which affects a greater proportion of women than men. P2X7 receptor activation contributes to arthritis, but whether it plays a role in articular inflammatory pain in a sex-dependent manner is unknown. We investigated whether the P2X7 receptor blockade in the knee joint of male and female rats reduces the articular hyperalgesia and inflammation induced by a carrageenan knee joint synovitis model. Articular hyperalgesia was quantified using the rat knee joint incapacitation test and the knee joint inflammation, characterized by the concentration of cytokines tumor necrosis factor-α, interleukin-1β, interleukin-6, and cytokine-induced neutrophil chemoattractant-1, and by neutrophil migration, was quantified using enzyme-linked immunosorbent assay and by myeloperoxidase enzyme activity measurement, respectively. P2X7 receptor blockade by the articular coadministration of selective P2X7 receptor antagonist A740003 with carrageenan significantly reduced articular hyperalgesia, pro-inflammatory cytokine concentrations, and myeloperoxidase activity induced by carrageenan injection into the knee joint of male and estrus female rats. However, a lower dose of P2X7 receptor antagonist was sufficient to significantly induce the antihyperalgesic and anti-inflammatory effects in estrus female but not in male rats. These results suggest that P2X7 receptor activation by endogenous adenosine 5'-triphosphate is essential to articular hyperalgesia and inflammation development in the knee joint of male and female rats. However, female rats are more responsive than male rats to the antihyperalgesic and anti-inflammatory effects induced by P2X7 receptor blockade. P2X7 receptors could be promising therapeutic targets in the treatment of knee joint disease symptoms, especially in women, who are more affected than men by these conditions. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

Gunshot wounds: epidemiology, wound ballistics, and soft-tissue treatment.

PubMed

Dougherty, Paul J; Najibi, Soheil; Silverton, Craig; Vaidya, Rahul

2009-01-01

The extremities are the most common anatomic location for gunshot wounds. Because of the prevalence of gunshot injuries, it is important that orthopaedic surgeons are knowledgeable about caring for them. The most common injuries seen with gunshot wounds are those of the soft tissues. Nonsurgical management of patients who have gunshot wounds with minimal soft-tissue disruption has been successfully accomplished in emergency departments for several years; this includes extremity wounds without nerve, intra-articular, or vascular injury. Stable, nonarticular fractures of an extremity have also been successfully treated with either minimal surgical or nonsurgical methods in the emergency department. Indications for surgical treatment include unstable fractures, intra-articular injuries, a significant soft-tissue injury (especially with skin loss), vascular injury, and/or a large or expanding hematoma.

Interspecific scaling patterns of talar articular surfaces within primates and their closest living relatives

PubMed Central

Yapuncich, Gabriel S; Boyer, Doug M

2014-01-01

The articular facets of interosseous joints must transmit forces while maintaining relatively low stresses. To prevent overloading, joints that transmit higher forces should therefore have larger facet areas. The relative contributions of body mass and muscle-induced forces to joint stress are unclear, but generate opposing hypotheses. If mass-induced forces dominate, facet area should scale with positive allometry to body mass. Alternatively, muscle-induced forces should cause facets to scale isometrically with body mass. Within primates, both scaling patterns have been reported for articular surfaces of the femoral and humeral heads, but more distal elements are less well studied. Additionally, examination of complex articular surfaces has largely been limited to linear measurements, so that ‘true area' remains poorly assessed. To re-assess these scaling relationships, we examine the relationship between body size and articular surface areas of the talus. Area measurements were taken from microCT scan-generated surfaces of all talar facets from a comprehensive sample of extant euarchontan taxa (primates, treeshrews, and colugos). Log-transformed data were regressed on literature-derived log-body mass using reduced major axis and phylogenetic least squares regressions. We examine the scaling patterns of muscle mass and physiological cross-sectional area (PCSA) to body mass, as these relationships may complicate each model. Finally, we examine the scaling pattern of hindlimb muscle PCSA to talar articular surface area, a direct test of the effect of mass-induced forces on joint surfaces. Among most groups, there is an overall trend toward positive allometry for articular surfaces. The ectal (= posterior calcaneal) facet scales with positive allometry among all groups except ‘sundatherians', strepsirrhines, galagids, and lorisids. The medial tibial facet scales isometrically among all groups except lemuroids. Scaling coefficients are not correlated with sample size, clade inclusivity or behavioral diversity of the sample. Muscle mass scales with slight positive allometry to body mass, and PCSA scales at isometry to body mass. PCSA generally scales with negative allometry to articular surface area, which indicates joint surfaces increase faster than muscles' ability to generate force. We suggest a synthetic model to explain the complex patterns observed for talar articular surface area scaling: whether ‘muscles or mass' drive articular facet scaling is probably dependent on the body size range of the sample and the biological role of the facet. The relationship between ‘muscle vs. mass' dominance is likely bone-and facet-specific, meaning that some facets should respond primarily to stresses induced by larger body mass, whereas others primarily reflect muscle forces. PMID:24219027

Histopathology of chondronecrosis development in knee articular cartilage in a rat model of Kashin-Beck disease using T-2 toxin and selenium deficiency conditions.

PubMed

Guan, Fang; Li, Siyuan; Wang, Zhi-Lun; Yang, Haojie; Xue, Senghai; Wang, Wei; Song, Daiqing; Zhou, Xiaorong; Zhou, Wang; Chen, Jing-Hong; Caterson, Bruce; Hughes, Clare

2013-01-01

The objective of this study is to observe pathogenic lesions of joint cartilages in rats fed with T-2 toxin under a selenium deficiency nutrition status in order to determine possible etiological factors causing Kashin-Beck disease (KBD). Sprague-Dawley rats were fed selenium-deficient or control diets for 4 weeks prior to their being exposed to T-2 toxin. Six dietary groups were formed and studied 4 weeks later, i.e., controls, selenium-deficient, low T-2 toxin, high T-2 toxin, selenium-deficient diet plus low T-2 toxin, and selenium-deficient diet plus high T-2 toxin. Selenium deficiencies were confirmed by the determination of glutathione peroxidase activity and selenium levels in serum. The morphology and pathology (chondronecrosis) of knee joint cartilage of experimental rats were observed using light microscopy and the expression of proteoglycans was determined by histochemical staining. Chondronecrosis in deep zone of articular cartilage of knee joints was seen in both the low and high T-2 toxin plus selenium-deficient diet groups, these chondronecrotic lesions being very similar to chondronecrosis observed in human KBD. However, the chondronecrosis observed in the rat epiphyseal growth plates of animals treated with T-2 toxin alone or T-2 toxin plus selenium-deficient diets were not similar to that found in human KBD. Our results indicate that the rat can be used as a suitable animal model for studying etiological factors contributing to the pathogenesis (chondronecrosis) observed in human KBD. However, those changes seen in epiphyseal growth plate differ from those seen in human KBD probably because of the absence of growth plate closure in the rat.

Human platelet lysate successfully promotes proliferation and subsequent chondrogenic differentiation of adipose-derived stem cells: a comparison with articular chondrocytes.

PubMed

Hildner, F; Eder, M J; Hofer, K; Aberl, J; Redl, H; van Griensven, M; Gabriel, C; Peterbauer-Scherb, A

2015-07-01

Fetal calf serum (FCS) bears a potential risk for carrying diseases and eliciting immune reactions. Nevertheless, it still represents the gold standard as medium supplement in cell culture. In the present study, human platelet lysate (PL) was tested as an alternative to FCS for the expansion and subsequent chondrogenic differentiation of human adipose-derived stem cells (ASCs). ASCs were expanded with 10% FCS (group F) or 5% PL (group P). Subsequently, three-dimensional (3D) micromass pellets were created and cultured for 5 weeks in chondrogenic differentiation medium. Additionally, the de- and redifferentiation potential of human articular chondrocytes (HACs) was evaluated and compared to ASCs. Both HACs and ASCs cultured with PL showed strongly enhanced proliferation rates. Redifferentiation of HACs was possible for cells expanded up to 3.3 population doublings (PD). At this stage, PL-expanded HACs demonstrated better redifferentiation potential than FCS-expanded cells. ASCs could also be differentiated following extended passaging. Glycosaminoglycan (GAG) quantification and qRT-PCR of 10 cartilage related markers demonstrated a tendency for increased chondrogenic differentiation of PL-expanded ASCs compared to cells expanded with FCS. Histologically, collagen type II but also collagen type X was mainly present in group P. The present study demonstrates that PL strongly induces proliferation of ASCs, while the chondrogenic differentiation potential is retained. HACs also showed enhanced proliferation and even better redifferentiation when previously expanded with PL. This suggests that PL is superior to FCS as a supplement for the expansion of ASCs and HACs, particularly with regard to chondrogenic (re)differentiation. Copyright © 2013 John Wiley & Sons, Ltd.

Replacing Shox2 with human SHOX leads to congenital disc degeneration of the temporomandibular joint in mice

PubMed Central

Li, Xihai; Liu, Hongbing; Gu, Shuping; Liu, Chao; Sun, Cheng; Zheng, Yuqian; Chen, YiPing

2013-01-01

The temporomandibular joint (TMJ) consists of the glenoid fossa arising from the otic capsule through intramembranous ossification, the fibrocartilaginous disc and the condyle, derived from the secondary cartilage by endochondral ossification. We have reported previously that cranial neural crest-specific inactivation of the homeobox gene Shox2, which is expressed in the mesenchymal cells of maxilla-mandibular junction and later in the progenitor cells and perichondrium of the developing chondyle, led to dysplasia and ankylosis of the TMJ, and replacement of the mouse Shox2 with the human SHOX gene rescued the dysplastic and ankylosis phenotypes but developed a prematurely worn out articular disc. In this study, we investigated the molecular and cellular bases for the premature wear out articular disc in the TMJ of mice carrying the human SHOX replacement allele in the Shox2 locus (referred as Shox2SHOX-KI/KI). We found that the developmental process and expression of several key genes in the TMJ of Shox2SHOX-KI/KI mice appeared similar to the controls. However, the disc of the Shox2SHOX-KI/KI TMJ exhibited a reduced level of Col I and Aggrecan, accompanied by increased activities of matrix metalloproteinases (MMPs) and a down-regulation of Ihh expression. Dramatically increased cell apoptosis in the disc was also observed. These combinatory cellular and molecular defects appear to contribute to the observed disc phenotype, suggesting that while the human SHOX can exert similar function as the mouse Shox2 in regulating early TMJ development, it apparently has a distinct function in the regulation of those molecules that are involved in tissue homeostasis. PMID:24248941

Development and morphogenesis of human wrist joint during embryonic and early fetal period

PubMed Central

Hita-Contreras, Fidel; Martínez-Amat, Antonio; Ortiz, Raúl; Caba, Octavio; Álvarez, Pablo; Prados, José C; Lomas-Vega, Rafael; Aránega, Antonia; Sánchez-Montesinos, Indalecio; Mérida-Velasco, Juan A

2012-01-01

The development of the human wrist joint has been studied widely, with the main focus on carpal chondrogenesis, ligaments and triangular fibrocartilage. However, there are some discrepancies concerning the origin and morphogenetic time-table of these structures, including nerves, muscles and vascular elements. For this study we used serial sections of 57 human embryonic (n = 30) and fetal (n = 27) specimens from O’Rahilly stages 17–23 and 9–14 weeks, respectively. The following phases in carpal morphogenesis have been established: undifferentiated mesenchyme (stage 17), condensated mesenchyme (stages 18 and 19), pre-chondrogenic (stages 19 and 20) and chondrogenic (stages 21 and over). Carpal chondrification and osteogenic processes are similar, starting with capitate and hamate (stage 19) and ending with pisiform (stage 22). In week 14, a vascular bud penetrates into the lunate cartilaginous mold, early sign of the osteogenic process that will be completed after birth. In stage 18, median, ulnar and radial nerves and thenar eminence appear in the hand plate. In stage 21, there are indications of the interosseous muscles, and in stage 22 flexor digitorum superficialis, flexor digitorum profundus and lumbrical muscles, transverse carpal ligament and collateral ligaments emerge. In stage 23, the articular disc, radiocarpal and ulnocarpal ligaments and deep palmar arterial arch become visible. Radiate carpal and interosseous ligaments appear in week 9, and in week 10, dorsal radiocarpal ligament and articular capsule are evident. Finally, synovial membrane is observed in week 13. We have performed a complete analysis of the morphogenesis of the structures of the human wrist joint. Our results present new data on nervous and arterial elements and provide the basis for further investigations on anatomical pathology, comparative morphology and evolutionary anthropology. PMID:22428933

Articular Joint Lubricants during Osteoarthritis and Rheumatoid Arthritis Display Altered Levels and Molecular Species

PubMed Central

Liebisch, Gerhard; Zhang, Ruiyan; Siebert, Hans-Christian; Wilhelm, Jochen; Kaesser, Ulrich; Dettmeyer, Reinhard B.; Klein, Heiko; Ishaque, Bernd; Rickert, Markus; Schmitz, Gerd; Schmidt, Tannin A.; Steinmeyer, Juergen

2015-01-01

Background Hyaluronic acid (HA), lubricin, and phospholipid species (PLs) contribute independently or together to the boundary lubrication of articular joints that is provided by synovial fluid (SF). Our study is the first reporting quantitative data about the molecular weight (MW) forms of HA, lubricin, and PLs in SF from cohorts of healthy donors, patients with early (eOA)- or late (lOA)-stage osteoarthritis (OA), and patients with active rheumatoid arthritis (RA). Methods We used human SF from unaffected controls, eOA, lOA, and RA. HA and lubricin levels were measured by enzyme-linked immunosorbent assay. PLs was quantified by electrospray ionization tandem mass spectrometry. Fatty acids (FAs) were analyzed by gas chromatography, coupled with mass spectrometry. The MW distribution of HA was determined by agarose gel electrophoresis. Results Compared with control SF, the concentrations of HA and lubricin were lower in OA and RA SF, whereas those of PLs were higher in OA and RA SF. Moreover, the MW distribution of HA shifted toward the lower ranges in OA and RA SF. We noted distinct alterations between cohorts in the relative distribution of PLs and the degree of FA saturation and chain lengths of FAs. Conclusions The levels, composition, and MW distribution of all currently known lubricants in SF—HA, lubricin, PLs—vary with joint disease and stage of OA. Our study is the first delivering a comprehensive view about all joint lubricants during health and widespread joint diseases. Thus, we provide the framework to develop new optimal compounded lubricants to reduce joint destruction. PMID:25933137

Changes in Cartilage Morphology of the Knee after 14-days of Bed Rest

NASA Astrophysics Data System (ADS)

Liphardt, A.-M.; Mündermann, A.; Koo, S.; Bäcker, N.; Andriacchi, T.; Zange, J.; Mester, J.; Heer, M.

Introduction While there are still many unanswered questions related to the effects of space flight and disuse on cartilage health and cartilage morphology the number of in vivo experiments in humans is small For muscle and bone tissue it is well known that unloading results in degeneration of those tissues Also for cartilage previous studies in patients suggest that unloading causes cartilage degeneration Studies using immobilization as a model of unloading help to investigate the importance of experiencing mechanical loads for the maintenance of healthy biological tissues The goal of our study was to investigate whether bed rest induced immobilization has a negative effect on articular cartilage in healthy subjects and if vibration training is a potential counter-measure for these negative effects Methods Eight male healthy subjects 78 1 pm 9 5 kg 179 pm 9 6 cm 26 pm 5 years performed a 14-day bed rest in 6 r -head down tilt HDT The study was designed in a cross-over-design where each subject received a training intervention vib in one phase and no intervention con in the other phase During the training intervention subjects trained 2 x 5-minutes per day at 20 Hz with 2 -- 4 mm amplitude on a vibration plate Galileo 900 Magnet resonance MR imaging of the right knee was performed to measure articular cartilage thickness MR-images 2 mm slice thickness 0 35 mm x 0 35 mm in-plane resolution 448 x 512 pixels were taken before and after bed rest to investigate the effects of bed rest

Blends and Nanocomposite Biomaterials for Articular Cartilage Tissue Engineering

PubMed Central

Doulabi, Azadehsadat Hashemi; Mequanint, Kibret; Mohammadi, Hadi

2014-01-01

This review provides a comprehensive assessment on polymer blends and nanocomposite systems for articular cartilage tissue engineering applications. Classification of various types of blends including natural/natural, synthetic/synthetic systems, their combination and nanocomposite biomaterials are studied. Additionally, an inclusive study on their characteristics, cell responses ability to mimic tissue and regenerate damaged articular cartilage with respect to have functionality and composition needed for native tissue, are also provided. PMID:28788131

Pathomechanics of Post-Traumatic OA Development in the Military Following Articular Fracture

DTIC Science & Technology

2016-10-01

post -op CT) associated with IAFs, but more patient data are needed to make the risk models clinically useful. Prospective studies of PTOA...AWARD NUMBER: W81XWH-15-2-0087 TITLE: Pathomechanics of Post -Traumatic OA Development in the Military Following Articular Fracture PRINCIPAL...29 Sep 2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Pathomechanics of Post -Traumatic OA Development in the Military Following Articular Fracture

The biological effects of sex hormones on rabbit articular chondrocytes from different genders.

PubMed

Chang, Shwu Jen; Kuo, Shyh Ming; Lin, Yen Ting; Yang, Shan-Wei

2014-01-01

The aim of this study was to investigate the biological effects of sex hormones (17β-estradiol and testosterone) on rabbit articular chondrocytes from different genders. We cultured primary rabbit articular chondrocytes from both genders with varying concentration of sex hormones. We evaluate cell proliferation and biochemical functions by MTT and GAG assay. The chondrocyte function and phenotypes were analyzed by mRNA level using RT-PCR. Immunocytochemical staining was also used to evaluate the generation of collagen-II. This study demonstrated that 17β-estradiol had greater positive regulation on the biological function and gene expressions of articular chondrocytes than testosterone, with the optimal concentrations of 10(-6) and 10(-7) M, particularly for female chondrocytes.

Juxta-articular osteoid osteoma of the talar neck: a case report.

PubMed

Mavrogenis, Andreas F; Dimitriou, Rozalia; Benetos, Ioannis S; Korres, Demetrios S; Papagelopoulos, Panayiotis J

2010-10-01

Juxta-articular osteoid osteomas of the ankle are rare and tend to have an atypical presentation. Because of the proximity to the joint, patients experience symptoms that may delay or mislead the diagnosis. This article presents a 33-year-old man with juxta-articular osteoid osteoma of the talar neck. The correct diagnosis was delayed for 2 years; the patient was initially misdiagnosed and treated for ankle sprain and anterior ankle impingement. Surgical excision of the lesion was performed with excellent results. Juxta-articular osteoid osteomas should be considered in the differential diagnosis of persistent ankle pain in teenagers and young adults who do not respond to treatment directed at more common conditions. Copyright © 2010 Elsevier Inc. All rights reserved.

Direct adenovirus-mediated gene delivery to the temporomandibular joint in guinea-pigs.

PubMed

Kuboki, T; Nakanishi, T; Kanyama, M; Sonoyama, W; Fujisawa, T; Kobayashi, K; Ikeda, T; Kubo, T; Yamashita, A; Takigawa, M

1999-09-01

Adenovirus vector system is expected to be useful for direct gene therapy for joint disease. This study first sought to confirm that foreign genes can be transferred to articular chondrocytes in primary culture. Next, recombinant adenovirus vectors harbouring beta-galactosidase gene (LacZ) was injected directly into the temporomandibular joints of Hartley guinea-pigs to clarify the in vivo transfer availability of the adenovirus vectors. Specifically, recombinant adenovirus harbouring LacZ gene (AxlCALacZ) was injected into the upper joint cavities of both mandibular joints of four male 6-week-old Hartley guinea-pigs. Either the same amount of recombinant adenovirus without LacZ gene (Axlw) suspension (placebo) or the same amount of phosphate-buffered saline solution (control) were injected into the upper joint cavities of both joints of another four male guinea-pigs. At 1, 2, 3 and 4 weeks after injection, the joints were dissected and the expression of delivered LacZ was examined by 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-gal) staining and reverse transcriptase-polymerase chain reaction (RT-PCR). To investigate the expression of transferred gene in other organs, total RNA was extracted from liver, kidney, heart and brain and the expression of LacZ mRNA and 18 S ribosomal RNA were analysed by RT-PCR. Clear expression of LacZ was observed in the articular surfaces of the temporal tubercle, articular disc and synovium of the temporomandibular joints even 4 weeks after injection in the AxlCALacZ-injected group, while no expression was detected in placebo and control groups. Histological examination confirmed that LacZ activity was clearly detected in a few cell layers of the articular surface tissues, which is much more efficient than in a previously study of the knee joint. In the other organs, expression of the delivered transgene was not observed. Based on these findings, direct gene delivery into the articular surface of the temporomandibular joint using the adenovirus vector is feasible as an effective in vivo method.

Can Signal Abnormalities Detected with MR Imaging in Knee Articular Cartilage Be Used to Predict Development of Morphologic Cartilage Defects? 48-Month Data from the Osteoarthritis Initiative

PubMed Central

Gersing, Alexandra S.; Mbapte Wamba, John; Nevitt, Michael C.; McCulloch, Charles E.; Link, Thomas M.

2016-01-01

Purpose To determine the incidence with which morphologic articular cartilage defects develop over 48 months in cartilage with signal abnormalities at baseline magnetic resonance (MR) imaging in comparison with the incidence in articular cartilage without signal abnormalities at baseline. Materials and Methods The institutional review boards of all participating centers approved this HIPAA-compliant study. Right knees of 90 subjects from the Osteoarthritis Initiative (mean age, 55 years ± 8 [standard deviation]; 51% women) with cartilage signal abnormalities but without morphologic cartilage defects at 3.0-T MR imaging and without radiographic osteoarthritis (Kellgren-Lawrence score, 0–1) were frequency matched for age, sex, Kellgren-Lawrence score, and body mass index with right knees in 90 subjects without any signal abnormalities or morphologic defects in the articular cartilage (mean age, 54 years ± 5; 51% women). Individual signal abnormalities (n = 126) on intermediate-weighted fast spin-echo MR images were categorized into four subgrades: subgrade A, hypointense; subgrade B, inhomogeneous; subgrade C, hyperintense; and subgrade D, hyperintense with swelling. The development of morphologic articular cartilage defects (Whole-Organ MR Imaging Score ≥2) at 48 months was analyzed on a compartment level and was compared between groups by using generalized estimating equation logistic regression models. Results Cartilage signal abnormalities were more frequent in the patellofemoral joint than in the tibiofemoral joint (59.5% vs 39.5%). Subgrade A was seen more frequently than were subgrades C and D (36% vs 22%). Incidence of morphologic cartilage defects at 48 months was 57% in cartilage with baseline signal abnormalities, while only 4% of compartments without baseline signal abnormalities developed morphologic defects at 48 months (all compartments combined and each compartment separately, P < .01). The development of morphologic defects was not significantly more likely in any of the subgrades (P = .98) and was significantly associated with progression of bone marrow abnormalities (P = .002). Conclusion Knee cartilage signal abnormalities detected with MR imaging are precursors of morphologic defects with osteoarthritis and may serve as imaging biomarkers with which to assess risk for cartilage degeneration. © RSNA, 2016 PMID:27135833

Fatigue Failure in Extra-Articular Proximal Tibia Fractures: Locking Intramedullary Nail Versus Double Locking Plates-A Biomechanical Study.

PubMed

Kandemir, Utku; Herfat, Safa; Herzog, Mary; Viscogliosi, Paul; Pekmezci, Murat

2017-02-01

The goal of this study is to compare the fatigue strength of a locking intramedullary nail (LN) construct with a double locking plate (DLP) construct in comminuted proximal extra-articular tibia fractures. Eight pairs of fresh frozen cadaveric tibias with low bone mineral density [age: 80 ± 7 (SD) years, T-score: -2.3 ± 1.2] were used. One tibia from each pair was fixed with LN, whereas the contralateral side was fixed with DLP for complex extra-articular multifragmentary metaphyseal fractures (simulating OTA 41-A3.3). Specimens were cyclically loaded under compression simulating single-leg stance by staircase method out to 260,000 cycles. Every 2500 cycles, localized gap displacements were measured with a 3D motion tracking system, and x-ray images of the proximal tibia were acquired. To allow for mechanical settling, initial metrics were calculated at 2500 cycles. The 2 groups were compared regarding initial construct stiffness, initial medial and lateral gap displacements, stiffness at 30,000 cycles, medial and lateral gap displacements at 30,000 cycles, failure load, number of cycles to failure, and failure mode. Failure metrics were reported for initial and catastrophic failures. DLP constructs exhibited higher initial stiffness and stiffness at 30,000 cycles compared with LN constructs (P < 0.03). There were no significant differences between groups for loads at failure or cycles to failure. For the fixation of extra-articular proximal tibia fractures, a LN provides a similar fatigue performance to double locked plates. The locked nail could be safely used for fixation of proximal tibia fractures with the advantage of limited extramedullary soft tissue damage.

Hyaline Articular Matrix Formed by Dynamic Self-Regenerating Cartilage and Hydrogels.

PubMed

Meppelink, Amanda M; Zhao, Xing; Griffin, Darvin J; Erali, Richard; Gill, Thomas J; Bonassar, Lawrence J; Redmond, Robert W; Randolph, Mark A

2016-07-01

Injuries to the articular cartilage surface are challenging to repair because cartilage possesses a limited capacity for self-repair. The outcomes of current clinical procedures aimed to address these injuries are inconsistent and unsatisfactory. We have developed a novel method for generating hyaline articular cartilage to improve the outcome of joint surface repair. A suspension of 10(7) swine chondrocytes was cultured under reciprocating motion for 14 days. The resulting dynamic self-regenerating cartilage (dSRC) was placed in a cartilage ring and capped with fibrin and collagen gel. A control group consisted of chondrocytes encapsulated in fibrin gel. Constructs were implanted subcutaneously in nude mice and harvested after 6 weeks. Gross, histological, immunohistochemical, biochemical, and biomechanical analyses were performed. In swine patellar groove, dSRC was implanted into osteochondral defects capped with collagen gel and compared to defects filled with osteochondral plugs, collagen gel, or left empty after 6 weeks. In mice, the fibrin- and collagen-capped dSRC constructs showed enhanced contiguous cartilage matrix formation over the control of cells encapsulated in fibrin gel. Biochemically, the fibrin and collagen gel dSRC groups were statistically improved in glycosaminoglycan and hydroxyproline content compared to the control. There was no statistical difference in the biomechanical data between the dSRC groups and the control. The swine model also showed contiguous cartilage matrix in the dSRC group but not in the collagen gel and empty defects. These data demonstrate the survivability and successful matrix formation of dSRC under the mechanical forces experienced by normal hyaline cartilage in the knee joint. The results from this study demonstrate that dSRC capped with hydrogels successfully engineers contiguous articular cartilage matrix in both nonload-bearing and load-bearing environments.

Blocking VEGF with sFlt1 improves the chondrogenic potential of mouse skeletal muscle-derived stem cells

PubMed Central

Kubo, Seiji; Cooper, Gregory M.; Matsumoto, Tomoyuki; Phillippi, Julie A.; Corsi, Karin A.; Usas, Arvydas; Li, Guangheng; Fu, Freddie H.; Huard, Johnny

2010-01-01

Objective To investigate the effect of VEGF stimulation and the effect of blocking VEGF with its antagonist, sFlt1, on chondrogenesis using skeletal muscle-derived stem cells (MDSCs). Methods The direct effect of VEGF on the in vitro chondrogenic ability of mouse MDSCs was tested using a pellet culture system followed by quantitative real time PCR and histological analyses. Next, the effect of VEGF on chondrogenesis within the synovial joint was tested using genetically engineered MDSCs implanted into the rat osteochondral defect. In this model, MDSCs, transduced with a retroviral vector to express BMP4, were co-implanted with MDSCs transduced to express either VEGF or sFlt1 (a VEGF antagonist) to provide a gain- and loss-of VEGF function experimental design. Histological scoring was used to compare cartilage formation among the treatment groups. Results Hyaline-like cartilage matrix production was observed in both VEGF-treated and VEGF-blocked (sFlt1-treated) pellet cultures, but real-time PCR revealed that sFlt1 treatment improved the expression of chondrogenic genes in MDSCs that were stimulated to undergo chondrogenic differentiation with BMP4 and TGF-β3. In vivo testing of articular cartilage repair showed that VEGF-transduced MDSCs caused an arthritic change in the knee joint, and sFlt1 improved the MDSC-mediated repair of articular cartilage, compared to BMP4 alone. Conclusion sFlt1 gene therapy improved BMP4- and TGF-β3-induced chondrogenic gene expression of MDSCs in vitro, and improved the persistence of repaired articular cartilage by preventing vascularization and bone invasion into the repaired articular cartilage. PMID:19116905

Comparison of 2 fluid ingress/egress systems for canine stifle arthroscopy using computed tomography.

PubMed

Warnock, Jennifer J; Nemanic, Sarah; O'Donnell, Matthew D; Wiest, Jason E

2014-11-01

To evaluate volume of extra-articular fluid egress and complications associated with 2 fluid ingress/egress techniques for stifle arthroscopy. Ex vivo study. Canine cadavers (n = 14). Four cadavers (8 stifles) were used to validate 3D computed tomographic (CT) methods to quantify stifle joint intra- and extra-articular volumes of iodinated contrast medium. Ten canine cadavers (20 stifles) had preoperative CT, followed by stifle arthroscopy using a 10% solution of iodinated contrast enhanced ingress fluid delivered by pressure bag (2PB) or by arthroscopic peristaltic pump (3FP). All 3FP limbs had an additional fluid egress portal placed by cannula and obturator. Arthroscopy was limited to 20 minutes/joint. The volume of the contrast medium egress into the soft tissues was measured on postoperative 3D CT reconstructed images. Mean percentage of total ingress fluids administered that remained in the joint and extra-articular tissues postoperatively was 8.8 ± 1.2% in 3FP and 33.2 ± 8% in 2PB (P = .014). Two 3FP joints had 4-5 mm egress obturator tracks on the proximal medial trochlear ridge. Two 2PB joints had severe joint collapse from extracapsular fluid precluding further examination. Intermittent visual blurring by joint fluid mixing or fat pad fragmentation/dissolution was noted in 2PB joints. A superior technique was not identified: 2PB had greater egress fluid tissue accumulation, whereas 3FP had better viewing of intra-articular structures with less tissue egress fluid accumulation; however, cartilage damage was induced with the egress obturator. © Copyright 2014 by The American College of Veterinary Surgeons.

Engraftment of autologous bone marrow cells into the injured cranial cruciate ligament in dogs.

PubMed

Linon, E; Spreng, D; Rytz, U; Forterre, S

2014-12-01

Current research indicates that exogenous stem cells may accelerate reparative processes in joint disease but, no previous studies have evaluated whether bone marrow cells (BMCs) target the injured cranial cruciate ligament (CCL) in dogs. The objective of this study was to investigate engraftment of BMCs following intra-articular injection in dogs with spontaneous CCL injury. Autologous PKH26-labelled BMCs were injected into the stifle joint of eight client-owned dogs with CCL rupture. The effects of PKH26 staining on cell viability and PKH26 fluorescence intensity were analysed in vitro using a MTT assay and flow cytometry. Labelled BMCs in injured CCL tissue were identified using fluorescence microscopy of biopsies harvested 3 and 13 days after intra-articular BMC injection. The intensity of PKH26 fluorescence declines with cell division but was still detectable after 16 days. Labelling with PKH26 had no detectable effect on cell viability or proliferation. Only rare PKH26-positive cells were present in biopsies of the injured CCL in 3/7 dogs and in synovial fluid in 1/7 dogs. No differences in transforming growth factor-β1, and interleukin-6 before and after BMC treatment were found and no clinical complications were noted during a 1 year follow-up period. In conclusion, BMCs were shown to engraft to the injured CCL in dogs when injected into the articular cavity. Intra-articular application of PKH26-labelled cultured mesenchymal stem cells is likely to result in higher numbers of engrafted cells that can be tracked using this method in a clinical setting. Copyright © 2014 Elsevier Ltd. All rights reserved.

The Effect of Exercise on the Early Stages of Mesenchymal Stromal Cell-Induced Cartilage Repair in a Rat Osteochondral Defect Model

PubMed Central

Yamaguchi, Shoki; Aoyama, Tomoki; Ito, Akira; Nagai, Momoko; Iijima, Hirotaka; Tajino, Junichi; Zhang, Xiangkai; Kiyan, Wataru; Kuroki, Hiroshi

2016-01-01

The repair of articular cartilage is challenging owing to the restriction in the ability of articular cartilage to repair itself. Therefore, cell supplementation therapy is possible cartilage repair method. However, few studies have verified the efficacy and safety of cell supplementation therapy. The current study assessed the effect of exercise on early the phase of cartilage repair following cell supplementation utilizing mesenchymal stromal cell (MSC) intra-articular injection. An osteochondral defect was created on the femoral grooves bilaterally of Wistar rats. Mesenchymal stromal cells that were obtained from male Wistar rats were cultured in monolayer. After 4 weeks, MSCs were injected into the right knee joint and the rats were randomized into an exercise or no-exercise intervention group. The femurs were divided as follows: C group (no exercise without MSC injection); E group (exercise without MSC injection); M group (no exercise with MSC injection); and ME group (exercise with MSC injection). At 2, 4, and 8 weeks after the injection, the femurs were sectioned and histologically graded using the Wakitani cartilage repair scoring system. At 2 weeks after the injection, the total histological scores of the M and ME groups improved significantly compared with those of the C group. Four weeks after the injection, the scores of both the M and ME groups improved significantly. Additionally, the scores in the ME group showed a significant improvement compared to those in the M group. The improvement in the scores of the E, M, and ME groups at 8 weeks were not significantly different. The findings indicate that exercise may enhance cartilage repair after an MSC intra-articular injection. This study highlights the importance of exercise following cell transplantation therapy. PMID:26968036

The Effect of Exercise on the Early Stages of Mesenchymal Stromal Cell-Induced Cartilage Repair in a Rat Osteochondral Defect Model.

PubMed

Yamaguchi, Shoki; Aoyama, Tomoki; Ito, Akira; Nagai, Momoko; Iijima, Hirotaka; Tajino, Junichi; Zhang, Xiangkai; Kiyan, Wataru; Kuroki, Hiroshi

2016-01-01

The repair of articular cartilage is challenging owing to the restriction in the ability of articular cartilage to repair itself. Therefore, cell supplementation therapy is possible cartilage repair method. However, few studies have verified the efficacy and safety of cell supplementation therapy. The current study assessed the effect of exercise on early the phase of cartilage repair following cell supplementation utilizing mesenchymal stromal cell (MSC) intra-articular injection. An osteochondral defect was created on the femoral grooves bilaterally of Wistar rats. Mesenchymal stromal cells that were obtained from male Wistar rats were cultured in monolayer. After 4 weeks, MSCs were injected into the right knee joint and the rats were randomized into an exercise or no-exercise intervention group. The femurs were divided as follows: C group (no exercise without MSC injection); E group (exercise without MSC injection); M group (no exercise with MSC injection); and ME group (exercise with MSC injection). At 2, 4, and 8 weeks after the injection, the femurs were sectioned and histologically graded using the Wakitani cartilage repair scoring system. At 2 weeks after the injection, the total histological scores of the M and ME groups improved significantly compared with those of the C group. Four weeks after the injection, the scores of both the M and ME groups improved significantly. Additionally, the scores in the ME group showed a significant improvement compared to those in the M group. The improvement in the scores of the E, M, and ME groups at 8 weeks were not significantly different. The findings indicate that exercise may enhance cartilage repair after an MSC intra-articular injection. This study highlights the importance of exercise following cell transplantation therapy.

The Effect of Intra-Articular Meperidine and Bupivacaine 0.5% on Postoperative Pain of Arthroscopic Knee Surgery; a Randomized Double Blind Clinical Trial

PubMed Central

Imani, Farnad; Entezary, Saeidreza; Razi, Mohammad; Jafarian, Ali Akbar; Yousefshahi, Fardin; Etemadi, Hasan; Safari, Saeid

2015-01-01

Background: Arthroscopic knee surgeries have a painful postoperative course, which often necessitates acute pain management. Among different analgesia techniques, Intra-articular injection is the technique of choice for many pain specialists, based on its confined effect to the surgical site (knee), lack of systemic effects and promotion of safe early ambulation. Objectives: The aim of this study was to compare analgesic effects of intra-articular meperidine, bupivacaine 0.5% or their combination after knee arthroscopic surgery. Patients and Methods: Sixty ASA class I-II patients’ candidates for arthroscopy knee surgery enrolled in a randomized double blind study to receive either 20 mL of bupivacaine 0.5%; 100 mg meperidine (diluted in normal saline) or bupivacaine 0.5% along with 100 mg meperidine. A written informed consent was obtained from all patients. Postoperative analgesia duration, VAS at 2, 6, 12 and 24 hours, the first analgesic request time, total fentanyl consumption in first 24 hours, patients’ satisfaction and adverse effects were recorded. Results: The bupivacaine-meperidine group had better duration of postoperative analgesia (P = 0.001), latter first analgesic request (P ≤ 0.001), lower total fentanyl consumption in first 24 hours after the operation (P = 0.001), less mean VAS at 2 hours (P = 0.001) and more patients’ overall satisfaction (P = 0.01) compared with each medication alone. VAS at 6, 12 and 24 postoperative hours were not different between the groups of study. No adverse effects were observed. Conclusions: Although postoperative intra-articular meperidine is a better alternative for bupivacaine, their combination could improve their analgesic effects compared with each other alone. PMID:25830119

Release of oxygen radicals by articular chondrocytes: a study of luminol-dependent chemiluminescence and hydrogen peroxide secretion.

PubMed

Rathakrishnan, C; Tiku, K; Raghavan, A; Tiku, M L

1992-10-01

We previously established that normal articular chondrocytes, like macrophages, express class II major histocompatibility antigens, present antigen, and induce mixed and autologous lymphocyte stimulation. In a recent study using the trapped indicator 2',7'-dichlorofluorescein diacetate, we were able to measure levels of intracellular hydrogen peroxide within normal articular chondrocytes (J Immunol 245:690-696, 1990). In the present study, we utilized the technique of chemiluminescence and the biochemical method of quantitating hydrogen peroxide release to measure the production of reactive oxygen intermediates by articular chondrocytes. Chondrocytes, in suspension or adherent to coverslips, showed luminol-dependent chemiluminescence that was dependent on the number and viability of cells. There was a dose-dependent increase in chemiluminescence in response to soluble stimuli, such as phorbol myristate acetate (PMA), concanavalin A (ConA), and f-Met-Leu-Phe (FMLP). Azide inhibited chemiluminescence, suggesting that the light emission in chondrocytes is myeloperoxidase dependent. The antioxidant, catalase, inhibited chemiluminescence but superoxide dismutase had no effect, suggesting that luminol-dependent chemiluminescence in chondrocytes mostly measured hydrogen peroxide. Chemiluminescence was also observed in fragments of live cartilage tissue, indicating that chondrocytes that are cartilage matrix bound can generate the respiratory burst response. Using the scopoletin oxidation assay, we confirmed the release of increasing amounts of hydrogen peroxide by chondrocytes exposed to interleukin-1, rabbit interferon, and tumor necrosis factor alpha. Tumor necrosis factor alpha had both priming and enhancing effects on reactive oxygen intermediate production by chondrocytes. Reactive oxygen intermediates have been shown to play a significant role in matrix degradation. We suggest that reactive oxygen intermediates produced by chondrocytes play an important role in the degradation of matrix in arthritis.

Cartilage-targeting drug delivery: can electrostatic interactions help?

PubMed

Bajpayee, Ambika G; Grodzinsky, Alan J

2017-03-01

Current intra-articular drug delivery methods do not guarantee sufficient drug penetration into cartilage tissue to reach cell and matrix targets at the concentrations necessary to elicit the desired biological response. Here, we provide our perspective on the utilization of charge-charge (electrostatic) interactions to enhance drug penetration and transport into cartilage, and to enable sustained binding of drugs within the tissue's highly negatively charged extracellular matrix. By coupling drugs to positively charged nanocarriers that have optimal size and charge, cartilage can be converted from a drug barrier into a drug reservoir for sustained intra-tissue delivery. Alternatively, a wide variety of drugs themselves can be made cartilage-penetrating by functionalizing them with specialized positively charged protein domains. Finally, we emphasize that appropriate animal models, with cartilage thickness similar to that of humans, must be used for the study of drug transport and retention in cartilage.

Protective effect of sensory denervation in inflammatory arthritis (evidence of regulatory neuroimmune pathways in the arthritic joint)

PubMed Central

Kane, D; Lockhart, J; Balint, P; Mann, C; Ferrell, W; McInnes, I

2005-01-01

Case report: The patient developed arthritis mutilans in all digits of both hands with the exception of the left 4th finger, which had prior sensory denervation following traumatic nerve dissection. Plain radiography, ultrasonography and nerve conduction studies of the hands confirmed the absence of articular disease and sensory innervation in the left 4th digit. Methods: This relationship between joint innervation and joint inflammation was investigated experimentally by prior surgical sensory denervation of the medial aspect of the knee in six Wistar rats in which carrageenan induced arthritis was subsequently induced. Prior sensory denervation—with preservation of muscle function—prevented the development of inflammatory arthritis in the denervated knee. Discussion: Observations in human and animal inflammatory arthritis suggest that regulatory neuroimmune pathways in the joint are an important mechanism that modulates the clinical expression of inflammatory arthritis. PMID:15155371

Pain Management After Outpatient Anterior Cruciate Ligament Reconstruction: A Systematic Review of Randomized Controlled Trials.

PubMed

Secrist, Eric S; Freedman, Kevin B; Ciccotti, Michael G; Mazur, Donald W; Hammoud, Sommer

2016-09-01

Effective pain management after anterior cruciate ligament (ACL) reconstruction improves patient satisfaction and function. To collect and evaluate the available evidence from randomized controlled trials (RCTs) on pain control after ACL reconstruction. Systematic review. A systematic literature review was performed using PubMed, Medline, Google Scholar, UpToDate, Cochrane Reviews, CINAHL, and Scopus following PRISMA guidelines (July 2014). Only RCTs comparing a method of postoperative pain control to another method or placebo were included. A total of 77 RCTs met inclusion criteria: 14 on regional nerve blocks, 21 on intra-articular injections, 4 on intramuscular/intravenous injections, 12 on multimodal regimens, 6 on oral medications, 10 on cryotherapy/compression, 6 on mobilization, and 5 on intraoperative techniques. Single-injection femoral nerve blocks provided superior analgesia to placebo for up to 24 hours postoperatively; however, this also resulted in a quadriceps motor deficit. Indwelling femoral catheters utilized for 2 days postoperatively provided superior analgesia to a single-injection femoral nerve block. Local anesthetic injections at the surgical wound site or intra-articularly provided equivalent analgesia to regional nerve blocks. Continuous-infusion catheters of a local anesthetic provided adequate pain relief but have been shown to cause chondrolysis. Cryotherapy improved analgesia compared to no cryotherapy in 4 trials, while in 4 trials, ice water and water at room temperature provided equivalent analgesic effects. Early weightbearing decreased pain compared to delayed weightbearing. Oral gabapentin given preoperatively and oral zolpidem given for the first week postoperatively each decreased opioid consumption as compared to placebo. Ibuprofen reduced pain compared to acetaminophen. Oral ketorolac reduced pain compared to hydrocodone-acetaminophen. Regional nerve blocks and intra-articular injections are both effective forms of analgesia. Cryotherapy-compression appears to be beneficial, provided that intra-articular temperatures are sufficiently decreased. Early mobilization reduces pain symptoms. Gabapentin, zolpidem, ketorolac, and ibuprofen decrease opioid consumption. Despite the vast amount of high-quality evidence on this topic, further research is needed to determine the optimal multimodal approach that can maximize recovery while minimizing pain and opioid consumption. These results provide the best available evidence from RCTs on pain control regimens after ACL reconstruction. © 2015 The Author(s).

The Anatomic Midpoint of the Attachment of the Medial Patellofemoral Complex.

PubMed

Tanaka, Miho J; Voss, Andreas; Fulkerson, John P

2016-07-20

The medial patellofemoral ligament varies in attachment of its fibers to the patella and vastus intermedius tendon. Our aim was to identify and describe its anatomic midpoint. To account for the variability of the attachment site, we refer to it as the medial patellofemoral complex. Using AutoCAD software, we identified the midpoint of the medial patellofemoral complex attachment on photographs of 31 cadaveric knee dissections. The midpoint was referenced relative to the superior articular surface of the patella (P1) and was described in terms of the percentage of the patellar articular length distal to this point. A second point, at the junction of the medial border of the vastus intermedius tendon with the superior articular border of the patella, was identified (P2). The distances of the midpoint to P1 and P2 were calculated and were compared using paired t tests. Twenty-five images had appropriate quality and landmarks for digital analysis. The midpoint of the medial patellofemoral complex was located a mean (and standard deviation) of 2.3% ± 15.8% of the patellar articular length distal to the superior pole and was at or proximal to P1 in 12 knees. In all knees, the midpoint was at or proximal to P2. After exclusion of 2 knees with vastus intermedius tendon attachments only, the medial patellofemoral complex midpoint was closer to P2 (5.3% ± 8.6% of the patellar articular length) than to P1 (9.3% ± 8.5% of the patellar articular length) (p = 0.06). The midpoint of the medial patellofemoral complex was 2.3% of the articular length distal to the superior pole of the patella. Additionally, we describe an anatomic landmark at the junction of the medial border of the vastus intermedius tendon and the articular border of the patella that approximates the midpoint of this complex. Our study shows that the anatomic midpoint of the attachment of the medial patellofemoral complex is proximal to the junction of the medial vastus intermedius tendon and the articular border of the patella, suggesting that graft placement may be more anatomic on the vastus intermedius tendon rather than on the patella. Copyright © 2016 by The Journal of Bone and Joint Surgery, Incorporated.

A diagnostic system for articular cartilage using non-destructive pulsed laser irradiation.

PubMed

Sato, Masato; Ishihara, Miya; Kikuchi, Makoto; Mochida, Joji

2011-07-01

Osteoarthritis involves dysfunction caused by cartilage degeneration, but objective evaluation methodologies based on the original function of the articular cartilage remain unavailable. Evaluations for osteoarthritis are mostly based simply on patient symptoms or the degree of joint space narrowing on X-ray images. Accurate measurement and quantitative evaluation of the mechanical characteristics of the cartilage is important, and the tissue properties of the original articular cartilage must be clarified to understand the pathological condition in detail and to correctly judge the efficacy of treatment. We have developed new methods to measure some essential properties of cartilage: a photoacoustic measurement method; and time-resolved fluorescence spectroscopy. A nanosecond-pulsed laser, which is completely non-destructive, is focused onto the target cartilage and induces a photoacoustic wave that will propagate with attenuation and is affected by the viscoelasticity of the surrounding cartilage. We also investigated whether pulsed laser irradiation and the measurement of excited autofluorescence allow real-time, non-invasive evaluation of tissue characteristics. The decay time, during which the amplitude of the photoacoustic wave is reduced by a factor of 1/e, represents the key numerical value used to characterize and evaluate the viscoelasticity and rheological behavior of the cartilage. Our findings show that time-resolved laser-induced autofluorescence spectroscopy (TR-LIFS) is useful for evaluating tissue-engineered cartilage. Photoacoustic measurement and TR-LIFS, predicated on the interactions between optics and living organs, is a suitable methodology for diagnosis during arthroscopy, allowing quantitative and multidirectional evaluation of the original function of the cartilage based on a variety of parameters. Copyright © 2011 Wiley-Liss, Inc.

Histopomorphic Evaluation of Radiofrequency Mediated Débridement Chondroplasty

PubMed Central

Ganguly, Kumkum; McRury, Ian D; Goodwin, Peter M; Morgan, Roy E; Augé II, Wayne K

2010-01-01

The use of radiofrequency devices has become widespread for surgical ablation procedures. When ablation devices have been deployed in treatment settings requiring tissue preservation like débridement chondroplasty, adoption has been limited due to the collateral damage caused by these devices in healthy tissue surrounding the treatment site. Ex vivo radiofrequency mediated débridement chondroplasty was performed on osteochondral specimens demonstrating surface fibrillation obtained from patients undergoing knee total joint replacement. Three radiofrequency systems designed to perform débridement chondroplasty were tested each demonstrating different energy delivery methods: monopolar ablation, bipolar ablation, and non-ablation energy. Treatment outcomes were compared with control specimens as to clinical endpoint and histopomorphic characteristics. Fibrillated cartilage was removed in all specimens; however, the residual tissue remaining at the treatment site displayed significantly different characteristics attributable to radiofrequency energy delivery method. Systems that delivered ablation-based energies caused tissue necrosis and collateral damage at the treatment site including corruption of cartilage Superficial and Transitional Zones; whereas, the non-ablation system created a smooth articular surface with Superficial Zone maintenance and without chondrocyte death or tissue necrosis. The mechanism of radiofrequency energy deposition upon tissues is particularly important in treatment settings requiring tissue preservation. Ablation-based device systems can cause a worsened state of articular cartilage from that of pre-treatment. Non-ablation energy can be successful in modifying/preconditioning tissue during débridement chondroplasty without causing collateral damage. Utilizing a non-ablation radiofrequency system provides the ability to perform successful débridement chondroplasty without causing additional articular cartilage tissue damage and may allow for other cartilage intervention success. PMID:20721322

Characterization of articular cartilage by combining microscopic analysis with a fibril-reinforced finite-element model.

PubMed

Julkunen, Petro; Kiviranta, Panu; Wilson, Wouter; Jurvelin, Jukka S; Korhonen, Rami K

2007-01-01

Load-bearing characteristics of articular cartilage are impaired during tissue degeneration. Quantitative microscopy enables in vitro investigation of cartilage structure but determination of tissue functional properties necessitates experimental mechanical testing. The fibril-reinforced poroviscoelastic (FRPVE) model has been used successfully for estimation of cartilage mechanical properties. The model includes realistic collagen network architecture, as shown by microscopic imaging techniques. The aim of the present study was to investigate the relationships between the cartilage proteoglycan (PG) and collagen content as assessed by quantitative microscopic findings, and model-based mechanical parameters of the tissue. Site-specific variation of the collagen network moduli, PG matrix modulus and permeability was analyzed. Cylindrical cartilage samples (n=22) were harvested from various sites of the bovine knee and shoulder joints. Collagen orientation, as quantitated by polarized light microscopy, was incorporated into the finite-element model. Stepwise stress-relaxation experiments in unconfined compression were conducted for the samples, and sample-specific models were fitted to the experimental data in order to determine values of the model parameters. For comparison, Fourier transform infrared imaging and digital densitometry were used for the determination of collagen and PG content in the same samples, respectively. The initial and strain-dependent fibril network moduli as well as the initial permeability correlated significantly with the tissue collagen content. The equilibrium Young's modulus of the nonfibrillar matrix and the strain dependency of permeability were significantly associated with the tissue PG content. The present study demonstrates that modern quantitative microscopic methods in combination with the FRPVE model are feasible methods to characterize the structure-function relationships of articular cartilage.

Development of a Valid and Reliable Knee Articular Cartilage Condition-Specific Study Methodological Quality Score.

PubMed

Harris, Joshua D; Erickson, Brandon J; Cvetanovich, Gregory L; Abrams, Geoffrey D; McCormick, Frank M; Gupta, Anil K; Verma, Nikhil N; Bach, Bernard R; Cole, Brian J

2014-02-01

Condition-specific questionnaires are important components in evaluation of outcomes of surgical interventions. No condition-specific study methodological quality questionnaire exists for evaluation of outcomes of articular cartilage surgery in the knee. To develop a reliable and valid knee articular cartilage-specific study methodological quality questionnaire. Cross-sectional study. A stepwise, a priori-designed framework was created for development of a novel questionnaire. Relevant items to the topic were identified and extracted from a recent systematic review of 194 investigations of knee articular cartilage surgery. In addition, relevant items from existing generic study methodological quality questionnaires were identified. Items for a preliminary questionnaire were generated. Redundant and irrelevant items were eliminated, and acceptable items modified. The instrument was pretested and items weighed. The instrument, the MARK score (Methodological quality of ARticular cartilage studies of the Knee), was tested for validity (criterion validity) and reliability (inter- and intraobserver). A 19-item, 3-domain MARK score was developed. The 100-point scale score demonstrated face validity (focus group of 8 orthopaedic surgeons) and criterion validity (strong correlation to Cochrane Quality Assessment score and Modified Coleman Methodology Score). Interobserver reliability for the overall score was good (intraclass correlation coefficient [ICC], 0.842), and for all individual items of the MARK score, acceptable to perfect (ICC, 0.70-1.000). Intraobserver reliability ICC assessed over a 3-week interval was strong for 2 reviewers (≥0.90). The MARK score is a valid and reliable knee articular cartilage condition-specific study methodological quality instrument. This condition-specific questionnaire may be used to evaluate the quality of studies reporting outcomes of articular cartilage surgery in the knee.

Routine clinical knee MR reports: comparison of diagnostic performance at 1.5 T and 3.0 T for assessment of the articular cartilage.

PubMed

Mandell, Jacob C; Rhodes, Jeffrey A; Shah, Nehal; Gaviola, Glenn C; Gomoll, Andreas H; Smith, Stacy E

2017-11-01

Accurate assessment of knee articular cartilage is clinically important. Although 3.0 Tesla (T) MRI is reported to offer improved diagnostic performance, literature regarding the clinical impact of MRI field strength is lacking. The purpose of this study is to compare the diagnostic performance of clinical MRI reports for assessment of cartilage at 1.5 and 3.0 T in comparison to arthroscopy. This IRB-approved retrospective study consisted of 300 consecutive knees in 297 patients who had routine clinical MRI and arthroscopy. Descriptions of cartilage from MRI reports of 165 knees at 1.5 T and 135 at 3.0 T were compared with arthroscopy. The sensitivity, specificity, percent of articular surfaces graded concordantly, and percent of articular surfaces graded within one grade of the arthroscopic grading were calculated for each articular surface at 1.5 and 3.0 T. Agreement between MRI and arthroscopy was calculated with the weighted-kappa statistic. Significance testing was performed utilizing the z-test after bootstrapping to obtain the standard error. The sensitivity, specificity, percent of articular surfaces graded concordantly, and percent of articular surfaces graded within one grade were 61.4%, 82.7%, 62.2%, and 77.5% at 1.5 T and 61.8%, 80.6%, 59.5%, and 75.6% at 3.0 T, respectively. The weighted kappa statistic was 0.56 at 1.5 T and 0.55 at 3.0 T. There was no statistically significant difference in any of these parameters between 1.5 and 3.0 T. Factors potentially contributing to the lack of diagnostic advantage of 3.0 T MRI are discussed.

Full-thickness knee articular cartilage defects in national football league combine athletes undergoing magnetic resonance imaging: prevalence, location, and association with previous surgery.

PubMed

Nepple, Jeffrey J; Wright, Rick W; Matava, Matthew J; Brophy, Robert H

2012-06-01

To better define the prevalence and location of full-thickness articular cartilage lesions in elite football players undergoing knee magnetic resonance imaging (MRI) at the National Football League (NFL) Invitational Combine and assess the association of these lesions with previous knee surgery. We performed a retrospective review of all participants in the NFL Combine undergoing a knee MRI scan from 2005 to 2009. Each MRI scan was reviewed for evidence of articular cartilage disease. History of previous knee surgery including anterior cruciate ligament reconstruction, meniscal procedures, and articular cartilage surgery was recorded for each athlete. Knees with a history of previous articular cartilage restoration surgery were excluded from the analysis. A total of 704 knee MRI scans were included in the analysis. Full-thickness articular cartilage lesions were associated with a history of any previous knee surgery (P < .001) and, specifically, previous meniscectomy (P < .001) but not with anterior cruciate ligament reconstruction (P = .7). Full-thickness lesions were present in 27% of knees with a previous meniscectomy compared with 12% of knees without any previous meniscal surgery. Full-thickness lesions in the lateral compartment were associated with previous lateral meniscectomy (P < .001); a similar relation was seen for medial meniscus tears in the medial compartment (P = .01). Full-thickness articular cartilage lesions of the knee were present in 17.3% of elite American football players at the NFL Combine undergoing MRI. The lateral compartment appears to be at greater risk for full-thickness cartilage loss. Previous knee surgery, particularly meniscectomy, is associated with these lesions. Level IV, therapeutic case series. Copyright © 2012 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

It's time to change perspective! New diagnostic tools for lateral elbow pain.

PubMed

Arrigoni, P; Cucchi, D; Menon, A; Randelli, P

2017-12-01

The presence of intra-articular findings that may complement the extra-articular pathology in lateral epicondilytis has been suggested, and a role for minor instability of the elbow as part of the causative process of this disease has been postulated. This study was designed to describe two new clinical tests, aimed at detecting intra-articular pathology in patients affected by recalcitrant lateral epicondylitis and investigate their diagnostic performance. Ten patients suffering of atraumatic lateral elbow pain unresponsive to conservative treatment were considered in this study. Two clinical tests were developed and administrated prior to arthroscopy: Supination and Antero-Lateral pain Test (SALT); Posterior Elbow Pain by Palpation-Extension of the Radiocapitellar joint (PEPPER). Sensitivity, specificity, predictive values and accuracy of SALT and PEPPER as diagnostic tests for seven intra-articular findings were calculated. In 90% of the patients, at least one test was positive. All patients with signs of lateral ligamentous patholaxity or intra-articular abnormal findings had a positive response to at least one of the two tests. SALT proved to have a high sensitivity but a low specificity and is accurate in detecting the presence of intra-articular abnormal findings, especially synovitis. PEPPER test was sensible, specific and accurate in the detection of radial head chondropathy. Two new diagnostic tests (SALT and PEPPER) were specifically designed to evoke pain from intra-articular structures. These tests could be a valid support in the diagnostic algorithm of recalcitrant lateral elbow pain. Positive findings may be indicative of a minor instability of the lateral elbow condition. Diagnostic study, development of diagnostic criteria on basis of consecutive patients, level II.

Intra-articular nerve growth factor regulates development, but not maintenance, of injury-induced facet joint pain & spinal neuronal hypersensitivity.

PubMed

Kras, J V; Kartha, S; Winkelstein, B A

2015-11-01

The objective of the current study is to define whether intra-articular nerve growth factor (NGF), an inflammatory mediator that contributes to osteoarthritic pain, is necessary and sufficient for the development or maintenance of injury-induced facet joint pain and its concomitant spinal neuronal hyperexcitability. Male Holtzman rats underwent painful cervical facet joint distraction (FJD) or sham procedures. Mechanical hyperalgesia was assessed in the forepaws, and NGF expression was quantified in the C6/C7 facet joint. An anti-NGF antibody was administered intra-articularly in additional rats immediately or 1 day following facet distraction or sham procedures to block intra-articular NGF and test its contribution to initiation and/or maintenance of facet joint pain and spinal neuronal hyperexcitability. NGF was injected into the bilateral C6/C7 facet joints in separate rats to determine if NGF alone is sufficient to induce these behavioral and neuronal responses. NGF expression increases in the cervical facet joint in association with behavioral sensitivity after that joint's mechanical injury. Intra-articular application of anti-NGF immediately after a joint distraction prevents the development of both injury-induced pain and hyperexcitability of spinal neurons. Yet, intra-articular anti-NGF applied after pain has developed does not attenuate either behavioral or neuronal hyperexcitability. Intra-articular NGF administered to the facet in naïve rats also induces behavioral hypersensitivity and spinal neuronal hyperexcitability. Findings demonstrate that NGF in the facet joint contributes to the development of injury-induced joint pain. Localized blocking of NGF signaling in the joint may provide potential treatment for joint pain. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.