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Sample records for early articular cartilage

  1. Microscale surface friction of articular cartilage in early osteoarthritis.

    PubMed

    Desrochers, Jane; Amrein, Matthias W; Matyas, John R

    2013-09-01

    Articular cartilage forms the articulating surface of long bones and facilitates energy dissipation upon loading as well as joint lubrication and wear resistance. In normal cartilage, boundary lubrication between thin films at the cartilage surface reduces friction in the absence of interstitial fluid pressurization and fluid film lubrication by synovial fluid. Inadequate boundary lubrication is associated with degenerative joint conditions such as osteoarthritis (OA), but relations between OA and surface friction, lubrication and wear in boundary lubrication are not well defined. The purpose of the present study was to measure microscale boundary mode friction of the articular cartilage surface in an in vivo experimental model to better understand changes in cartilage surface friction in early OA. Cartilage friction was measured on the articular surface by atomic force microscopy (AFM) under applied loads ranging from 0.5 to 5 μN. Microscale AFM friction analyses revealed depth dependent changes within the top-most few microns of the cartilage surface in this model of early OA. A significant increase of nearly 50% was observed in the mean engineering friction coefficient for OA cartilage at the 0.5 μN load level; no significant differences in friction coefficients were found under higher applied loads. Changes in cartilage surface morphology observed by scanning electron microscopy included cracking and roughening of the surface indicative of disruption and wear accompanied by an apparent disintegration of the thin surface lamina from the underlying matrix. Immunohistochemical staining of lubricin - an important cartilage surface boundary lubricant - did not reveal differences in spatial distribution near the cartilage surface in OA compared to controls. The increase in friction at the 0.5 μN force level is interpreted to reflect changes in the interfacial mechanics of the thin surface lamina of articular cartilage: increased friction implies reduced

  2. [The early development of the articular cartilage. IV. The metamorphosing cartilage].

    PubMed

    Knese, K H

    1980-01-01

    The definite articular cartilage originate from 2 anlagen, the primordial tangential layer and the greater part including the joint bone plate from the metamorphosing cartilage. The tangential layer grow by apposition from the perichondrium. Additional the layer becomes also dilatated as a result of the growing volume of the ossification center. In this way the Lamina splendens with residues of cells may be formed. The chondrocytes resemble partly fibroblasts, in older animals possibly even tendocytes. Moreover the cells exhibit a varying different shape. Today it is impossible to interpret the polymorphism of the cells. In the primordial state, the chondrocyts are embedded in a network from thin cartilage fibrils. Later on collagen fibrils from varied thickness (up to 900 A) are formed. The fibrils run only partly parallel to each other, in general they form a network, in which they cross with a low angle. There are great local differences in the fibrillar structure by the same animal. PMID:7461420

  3. [Articular cartilage regeneration using scaffold].

    PubMed

    Ishimoto, Yoshiyuki; Hattori, Koji; Ohgushi, Hajime

    2008-12-01

    The self-healing capacity of articular cartilage for repair is limited. For articular cartilage injury, several surgical techniques are used in clinical practice, namely drilling, abrasion arthroplasty, microfracture, or autologous osteochondral grafting, while various methods of autologous chondrocyte transplantation to cartilage defect sites have been reported since 1990s. In a case of chondrocyte transplantation to cartilage defect site, the use of proper scaffold is important. Currently, collagen gel or PLGA is used widely as a scaffold. PMID:19043192

  4. Very early osteoarthritis changes sensitively fluid flow properties of articular cartilage.

    PubMed

    Mäkelä, J T A; Han, S-K; Herzog, W; Korhonen, R K

    2015-09-18

    In this study, fibril-reinforced poroelastic (FRPE) modeling was used for rabbit knee after anterior cruciate ligament transection (ACLT) to assess how the mechanical properties of collagen, proteoglycans, and fluid in articular cartilage change in early osteoarthritis, and how site-specific these changes are. Unilateral ACLT was performed in eight skeletally mature, female New Zealand white rabbits. A separate control (CTRL) group consisted of knee joints of five non-operated rabbits. Animals were sacrificed at four weeks after ACLT and cartilage-on-bone samples from femoral groove, medial and lateral femoral condyles, and tibial plateaus were harvested. A stress-relaxation protocol in indentation geometry was applied and the FRPE model was fitted to the experimental force-time curve by minimizing the mean absolute error between experiment and simulation. The optimized parameters were: fibril network modulus (Ef), representing the collagen network; non-fibrillar matrix modulus (Enf), representing the PG matrix; and permeability (k), representing fluid flow. Permeability was increased significantly in the ACLT group compared to the CTRL group knees at all sites except for the medial tibial plateau. ACLT also caused a decrease in the Ef at all sites except for the medial and lateral tibial plateaus. The Enf of the ACLT group knees was altered only for the lateral femoral condyle. The results of this study suggest that early osteoarthritis primarily affects cartilage permeability and impairs the collagen network stiffness in a site-specific manner. These findings from early osteoarthritis indicate that fluid flow velocity in articular cartilage may change prior to quantifiable structural alterations in the tissue. PMID:26159056

  5. 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

  6. Fracture of articular cartilage.

    PubMed

    Chin-Purcell, M V; Lewis, J L

    1996-11-01

    Crack formation and propagation is a significant element of the degeneration process in articular cartilage. In order to understand this process, and separate the relative importance of structural overload and material failure, methods for measuring the fracture toughness of cartilage are needed. In this paper, two such methods are described and used to measure fracture properties of cartilage from the canine patella. A modified single edge notch (MSEN) specimen was used to measure J, and a trouser tear test was used to measure T, both measures of fracture toughness with units of kN/m. A pseudo-elastic modulus was also obtained from the MSEN test. Several potential error sources were examined, and results for the MSEN test compared with another method for measuring the fracture parameter for urethane rubber. Good agreement was found. The two test methods were used to measure properties of cartilage from the patellae of 12 canines: 4-9 specimens from each of 12 patellae, with 5 right-left pairs were tested. Values of J ranged from 0.14-1.2 kN/m. J values correlated with T and were an average of 1.7 times larger than T. A variety of failure responses was seen in the MSEN tests, consequently a grade of 0 to 3 was assigned to each test, where 0 represented a brittle-like crack with minimal opening and 3 represented plastic flow with no crack formation. The initial cracks in 12/82 specimens did not propagate and were assigned to grade 3. The method for reducing data in the MSEN test assumed pseudo-elastic response and could not be used for the grade 3 specimens. Stiffness did not correlate with J. Neither J nor T was statistically different between right-left pairs, but varied between animals. The test methods appear useful for providing a quantitative measure of fracture toughness for cartilage and other soft materials. PMID:8950659

  7. Structural Variations in Articular Cartilage Matrix Are Associated with Early-Onset Osteoarthritis in the Spondyloepiphyseal Dysplasia Congenita (Sedc) Mouse

    PubMed Central

    Macdonald, David W.; Squires, Ryan S.; Avery, Shaela A.; Adams, Jason; Baker, Melissa; Cunningham, Christopher R.; Heimann, Nicholas B.; Kooyman, David L.; Seegmiller, Robert E.

    2013-01-01

    Heterozgyous spondyloepiphyseal dysplasia congenita (sedc/+) mice expressing a missense mutation in col2a1 exhibit a normal skeletal morphology but early-onset osteoarthritis (OA). We have recently examined knee articular cartilage obtained from homozygous (sedc/sedc) mice, which express a Stickler-like phenotype including dwarfism. We examined sedc/sedc mice at various levels to better understand the mechanistic process resulting in OA. Mutant sedc/sedc, and control (+/+) cartilages were compared at two, six and nine months of age. Tissues were fixed, decalcified, processed to paraffin sections, and stained with hematoxylin/eosin and safranin O/fast green. Samples were analyzed under the light microscope and the modified Mankin and OARSI scoring system was used to quantify the OA-like changes. Knees were stained with 1C10 antibody to detect the presence and distribution of type II collagen. Electron microscopy was used to study chondrocyte morphology and collagen fibril diameter. Compared with controls, mutant articular cartilage displayed decreased fibril diameter concomitant with increases in size of the pericellular space, Mankin and OARSI scores, cartilage thickness, chondrocyte clustering, proteoglycan staining and horizontal fissuring. In conclusion, homozygous sedc mice are subject to early-onset knee OA. We conclude that collagen in the mutant’s articular cartilage (both heterozygote and homozygote) fails to provide the normal meshwork required for matrix integrity and overall cartilage stability. PMID:23939426

  8. Engineering lubrication in articular cartilage.

    PubMed

    McNary, Sean M; Athanasiou, Kyriacos A; Reddi, A Hari

    2012-04-01

    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

  9. 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

  10. Micromechanical Mapping of Early Osteoarthritic Changes in the Pericellular Matrix of Human Articular Cartilage

    PubMed Central

    Wilusz, Rebecca E.; Zauscher, Stefan; Guilak, Farshid

    2013-01-01

    Objective Osteoarthritis (OA) is a degenerative joint disease characterized by the progressive loss of articular cartilage. While macroscale degradation of the cartilage extracellular matrix (ECM) has been extensively studied, microscale changes in the chondrocyte pericellular matrix (PCM) and immediate microenvironment with OA are not fully understood. The objective of this study was to quantify osteoarthritic changes in the micromechanical properties of the ECM and PCM of human articular cartilage in situ using atomic force microscopy (AFM). Method AFM elastic mapping was performed on cryosections of human cartilage harvested from both condyles of macroscopically normal and osteoarthritic knee joints. This method was used to test the hypotheses that both ECM and PCM regions exhibit a loss of mechanical properties with OA and that the size of the PCM is enlarged in OA cartilage as compared to normal tissue. Results Significant decreases were observed in both ECM and PCM moduli of 45% and 30%, respectively, on the medial condyle of OA knee joints as compared to cartilage from macroscopically normal joints. Enlargement of the PCM, as measured biomechanically, was also observed in medial condyle OA cartilage, reflecting the underlying distribution of type VI collagen in the region. No significant differences were observed in elastic moduli or their spatial distribution on the lateral condyle between normal and OA joints. Conclusion Our findings provide new evidence of significant site-specific degenerative changes in the chondrocyte micromechanical environment with OA. PMID:24025318

  11. [Imaging of articular cartilage].

    PubMed

    Arkun, Remide

    2007-01-01

    There have been many improvements in joint cartilage imaging in recent years with the development of new imaging methods. The purpose of cartilage imaging is to assess the integrity of the cartilage surface, the thickness and volume of the cartilage matrix and its relationship with the subchondral bone. Direct radiography, the conventional imaging method for the skeletal system, is not sufficient for assessing the joint cartilage, nor are arthrography, computed tomography, and arthrography together with computed tomography. Moreover, biomechanical changes in the joint cartilage cannot be assessed with these methods. Magnetic resonance imaging (MRI), with its superior contrast resolution and multiplanar imaging capability across tissues, has become the primary diagnostic method for assessment of joint pathologies. The morphological features of the joint cartilage can be assessed adequately with the use of MRI sequences specific to the cartilage. Appropriate use of MRI sequences to determine the type of cartilage damage, the presence and degree of accompanying pathologies in the subchondral bone will help minimize diagnostic errors. This article reviews cartilage imaging in the following aspects: the technique used in MRI for cartilage imaging, findings of cartilage pathology, and anticipation of future cartilage imaging. PMID:18180582

  12. Development of artificial articular cartilage.

    PubMed

    Oka, M; Ushio, K; Kumar, P; Ikeuchi, K; Hyon, S H; Nakamura, T; Fujita, H

    2000-01-01

    Attempts have been made to develop an artificial articular cartilage on the basis of a new viewpoint of joint biomechanics in which the lubrication and load-bearing mechanisms of natural and artificial joints are compared. Polyvinyl alcohol hydrogel (PVA-H), 'a rubber-like gel', was investigated as an artificial articular cartilage and the mechanical properties of this gel were improved through a new synthetic process. In this article the biocompatibility and various mechanical properties of the new improved PVA-H is reported from the perspective of its usefulness as an artificial articular cartilage. As regards lubrication, the changes in thickness and fluid pressure of the gap formed between a glass plate and the specimen under loading were measured and it was found that PVA-H had a thicker fluid film under higher pressures than polyethylene (PE) did. The momentary stress transmitted through the specimen revealed that PVA-H had a lower peak stress and a longer duration of sustained stress than PE, suggesting a better damping effect. The wear factor of PVA-H was approximately five times that of PE. Histological studies of the articular cartilage and synovial membranes around PVA-H implanted for 8-52 weeks showed neither inflammation nor degenerative changes. The artificial articular cartilage made from PVA-H could be attached to the underlying bone using a composite osteochondral device made from titanium fibre mesh. In the second phase of this work, the damage to the tibial articular surface after replacement of the femoral surface in dogs was studied. Pairs of implants made of alumina, titanium or PVA-H on titanium fibre mesh were inserted into the femoral condyles. The two hard materials caused marked pathological changes in the articular cartilage and menisci, but the hydrogel composite replacement caused minimal damage. The composite osteochondral device became rapidly attached to host bone by ingrowth into the supporting mesh. The clinical implications of

  13. Progression of Gene Expression Changes following a Mechanical Injury to Articular Cartilage as a Model of Early Stage Osteoarthritis

    PubMed Central

    McCulloch, R. S.; Ashwell, M. S.; Maltecca, C.; O'Nan, A. T.; Mente, P. L.

    2014-01-01

    An impact injury model of early stage osteoarthritis (OA) progression was developed using a mechanical insult to an articular cartilage surface to evaluate differential gene expression changes over time and treatment. Porcine patellae with intact cartilage surfaces were randomized to one of three treatments: nonimpacted control, axial impaction (2000 N), or a shear impaction (500 N axial, with tangential displacement to induce shear forces). After impact, the patellae were returned to culture for 0, 3, 7, or 14 days. At the appropriate time point, RNA was extracted from full-thickness cartilage slices at the impact site. Quantitative real-time PCR was used to evaluate differential gene expression for 18 OA related genes from four categories: cartilage matrix, degradative enzymes and inhibitors, inflammatory response and signaling, and cell apoptosis. The shear impacted specimens were compared to the axial impacted specimens and showed that shear specimens more highly expressed type I collagen (Col1a1) at the early time points. In addition, there was generally elevated expression of degradative enzymes, inflammatory response genes, and apoptosis markers at the early time points. These changes suggest that the more physiologically relevant shear loading may initially be more damaging to the cartilage and induces more repair efforts after loading. PMID:25478225

  14. Treatment and Prevention of (Early) Osteoarthritis Using Articular Cartilage Repair—Fact or Fiction? A Systematic Review

    PubMed Central

    de Windt, Tommy S.; Vonk, Lucienne A.; Brittberg, Mats

    2013-01-01

    Early osteoarthritis (OA) is increasingly being recognized in patients who wish to remain active while not accepting the limitations of conservative treatment or joint replacement. The aim of this systematic review was to evaluate the existing evidence for treatment of patients with early OA using articular cartilage repair techniques. A systematic search was performed in EMBASE, MEDLINE, and the Cochrane collaboration. Articles were screened for relevance and appraised for quality. Nine articles of generally low methodological quality (mean Coleman score 58) including a total of 502 patients (mean age range = 36-57 years) could be included. In the reports, both radiological and clinical criteria for early OA were applied. Of all patients included in this review, 75% were treated with autologous chondrocyte implantation. Good short-term clinical outcome up to 9 years was shown. Failure rates varied from 8% to 27.3%. The conversion to total knee arthroplasty rate was 2.5% to 6.5%. Although a (randomized controlled) trial in this patient category with long-term follow-up is needed, the literature suggests autologous chondrocyte implantation could provide good short- to mid-term clinical outcome and delay the need for total knee arthroplasty. The use of standardized criteria for early OA and implementation of (randomized) trials with long-term follow-up may allow for further expansion of the research field in articular cartilage repair to the challenging population with (early) OA. PMID:26069664

  15. 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

  16. 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

  17. Articular cartilage: structure and regeneration.

    PubMed

    Becerra, José; Andrades, José A; Guerado, Enrique; Zamora-Navas, Plácido; López-Puertas, José M; Reddi, A Hari

    2010-12-01

    Articular cartilage (AC) has no or very low ability of self-repair, and untreated lesions may lead to the development of osteoarthritis. One method that has been proven to result in long-term repair or isolated lesions is autologous chondrocyte transplantation. However, first generation of these cells' implantation has limitations, and introducing new effective cell sources can improve cartilage repair. AC provides a resilient and compliant articulating surface to the bones in diarthrodial joints. It protects the joint by distributing loads applied to it, so preventing potentially damaging stress concentrations on the bone. At the same time it provides a low-friction-bearing surface to enable free movement of the joint. AC may be considered as a visco- or poro-elastic fiber-composite material. Fibrils of predominantly type II collagen provide tensile reinforcing to a highly hydrated proteoglycan gel. The tissue typically comprises 70% water and it is the structuring and retention of this water by the proteoglycans and collagen that is largely responsible for the remarkable ability of the tissue to support compressive loads. PMID:20836752

  18. Surface of articular cartilage: immunohistological studies.

    PubMed

    Duance, V C

    1983-10-01

    Using several physical techniques the surface of articular cartilage has been reported to be structurally different from the deeper layers. In this paper using immunohistochemical methods, the surface has been shown to contain a characteristically different collagen, Type I in contrast to Type II which is the major collagen of cartilage. These results support previous proposals for a surface layer, or lamina splendens, the presence of which would be of considerable importance in understanding the degradation of cartilage in arthritides. PMID:6678620

  19. Matrilin-2 Is a Widely Distributed Extracellular Matrix Protein and a Potential Biomarker in the Early Stage of Osteoarthritis in Articular Cartilage

    PubMed Central

    Zhang, Shukun; Peng, Jinwu; Guo, Yan; Javidiparsijani, Sara; Wang, Guirong; Wang, Yichun; Liu, Honggang; Liu, Jingshi; Luo, Junming

    2014-01-01

    In this study, we first generated and characterized a polyclonal antibody against unique domain of matrlin-2 and then used this specific antibody to assess the expression pattern of matrilin-2 by immunohistochemistry. We found that marilin-2 is widely distributed in the connective tissues of many mouse tissues including heart, colon, penis, esophagus, lung, kidney, tracheal cartilage, developmental bone, and adult bone. The expression level of matrilin-2 was remarkably increased in the tissues of osteoarthritis developmental articular cartilage, compared to normal healthy tissues. Furthermore, we determined matrilin-2 expression in specific epithelial cells in stomach and ductal epithelial cells of salivary gland. In other tissues, the positive signals were mainly located around cardiac muscle cells and Purkinje fibers in the heart; corpus spongiosum in the penis; submucosa in the colon and esophagus; extracellular matrix of cartilage in the tracheal cartilage; and, glomerulus, the basement membrane of distal convoluted tubule and renal matrix in kidney. These observations indicated that the distribution pattern of matrilin-2 is heterogeneous in each tissue. Matrilin-2 may play an important role in the communication of matrix to matrix and matrix to cells and will be used as a potential biomarker in the early stage of osteoarthritis of articular cartilage. PMID:24741569

  20. Vitrification of intact human articular cartilage.

    PubMed

    Jomha, Nadr M; Elliott, Janet A W; Law, Garson K; Maghdoori, Babak; Forbes, J Fraser; Abazari, Alireza; Adesida, Adetola B; Laouar, Leila; Zhou, Xianpei; McGann, Locksley E

    2012-09-01

    Articular cartilage injuries do not heal and large defects result in osteoarthritis with major personal and socioeconomic costs. Osteochondral transplantation is an effective treatment for large joint defects but its use is limited by the inability to store cartilage for long periods of time. Cryopreservation/vitrification is one method to enable banking of this tissue but decades of research have been unable to successfully preserve the tissue while maintaining cartilage on its bone base - a requirement for transplantation. To address this limitation, human knee articular cartilage from total knee arthroplasty patients and deceased donors was exposed to specified concentrations of 4 different cryoprotective agents for mathematically determined periods of time at lowering temperatures. After complete exposure, the cartilage was immersed in liquid nitrogen for up to 3 months. Cell viability was 75.4 ± 12.1% determined by membrane integrity stains and confirmed with a mitochondrial assay and pellet culture documented production of sulfated glycosaminoglycans and collagen II similar to controls. This report documents successful vitrification of intact human articular cartilage on its bone base making it possible to bank this tissue indefinitely. PMID:22698720

  1. Body Weight Independently Affects Articular Cartilage Catabolism

    PubMed Central

    Denning, W. Matt; Winward, Jason G.; Pardo, Michael Becker; Hopkins, J. Ty; Seeley, Matthew K.

    2015-01-01

    Although obesity is associated with osteoarthritis, it is unclear whether body weight (BW) independently affects articular cartilage catabolism (i.e., independent from physiological factors that also accompany obesity). The primary purpose of this study was to evaluate the independent effect of BW on articular cartilage catabolism associated with walking. A secondary purpose was to determine how decreased BW influenced cardiovascular response due to walking. Twelve able-bodied subjects walked for 30 minutes on a lower-body positive pressure treadmill during three sessions: control (unadjusted BW), +40%BW, and -40%BW. Serum cartilage oligomeric matrix protein (COMP) was measured immediately before (baseline) and after, and 15 and 30 minutes after the walk. Heart rate (HR) and rate of perceived exertion (RPE) were measured every three minutes during the walk. Relative to baseline, average serum COMP concentration was 13% and 5% greater immediately after and 15 minutes after the walk. Immediately after the walk, serum COMP concentration was 14% greater for the +40%BW session than for the -40%BW session. HR and RPE were greater for the +40%BW session than for the other two sessions, but did not differ between the control and -40%BW sessions. BW independently influences acute articular cartilage catabolism and cardiovascular response due to walking: as BW increases, so does acute articular cartilage catabolism and cardiovascular response. These results indicate that lower-body positive pressure walking may benefit certain individuals by reducing acute articular cartilage catabolism, due to walking, while maintaining cardiovascular response. Key points Walking for 30 minutes with adjustments in body weight (normal body weight, +40% and -40% body weight) significantly influences articular cartilage catabolism, measured via serum COMP concentration. Compared to baseline levels, walking with +40% body weight and normal body weight both elicited significant increases in

  2. Distinguishing ankle and knee articular cartilage.

    PubMed

    Cole, Ada A; Margulis, Arkady; Kuettner, Klaus E

    2003-06-01

    Degenerative changes in the tall and femoral distal cartilages of more than 2,000 tissue donors were graded based on the appearance of articular cartilage and osteophytes. In the ankle and the knee the degenerative changes increased with age; however, the rate of degeneration in the ankle was slower than in the knee. The degenerative changes in the ankle were more severe in men than in women, were predominantly bilateral, and seemed to be correlated with weight. The slower rate of change in the ankle may be caused, in part, by the biochemical and biomechanical tissue properties that distinguish ankle cartilage from that of the knee. PMID:12911243

  3. Colonies in engineered articular cartilage express superior differentiation.

    PubMed

    Selvaratnam, L; Abd Rahim, S; Kamarul, T; Chan, K Y; Sureshan, S; Penafort, R; Ng, C L L

    2005-07-01

    In view of poor regeneration potential of the articular cartilage, in-vitro engineering of cartilage tissue offers a promising option for progressive joint disease. This study aims to develop a biologically engineered articular cartilage for autologous transplantation. The initial work involved determination of chondrocyte yield and viability, and morphological analysis. Cartilage was harvested from the knee, hip and shoulder joints of adult New Zealand white rabbits and chondrocytes were isolated by enzymatic digestion of the extra-cellular matrix before serial cultivation in DMEM/Ham's F12 media as monolayer cultures. No differences were noted in cell yield. Although chondrocytes viability was optimal (>93%) following harvest from native cartilage, their viability tended to be lowered on passaging. Chondrocytes aggregated in isogenous colonies comprising ovoid cells with intimate intracellular contacts and readily exhibited Safranin-O positive matrix; features typically associated with articular cartilage in-vivo. However, chondrocytes also existed concurrently in scattered bipolar/multipolar forms lacking Safranin-O expression. Therefore, early data demonstrated successful serial culture of adult chondrocytes with differentiated morphology seen in established chondrocyte colonies synthesizing matrix proteoglycans. PMID:16381284

  4. Effect of passive motion on articular cartilage in rat osteoarthritis

    PubMed Central

    QIAN, JIE; LIANG, JUN; WANG, YUBIN; WANG, HUIFANG

    2014-01-01

    The aim of the present study was to investigate the effect of moderate passive motion on articular cartilage in osteoarthritis (OA) caused by knee fracture. Sprague-Dawley rats (age, 8 weeks) with knee fractures were used to construct rat knee early- and middle-stage OA models. The stages were fixed for three and six weeks, with 20 rats analyzed at each stage. The experimental groups were exercised daily for 15 m/min with a specified duration. Following the completion of exercise, the effects of proper passive motion on cartilage thickness, the Mankin rating, cartilage collagen matrix, proteoglycan content and the morphological structure of the cartilage in the rat OA models were measured at the various degenerative stages caused by knee fracture. The proteoglycan content of the cartilage matrix, type II collagen fibers and the number of cartilage cells undergoing apoptosis were semiquantified. For early- and middle-stage OA, the cartilage layers in the three- or six-week experimental groups were significantly thicker and the levels of proteoglycans and type II collagen fibers in the weight-bearing area of the cartilage were significantly higher when compared with the control groups (P<0.05). In addition, the Mankin ratings were lower and ligament tension was increased when compared with the control group (P<0.05). In the early-stage OA group, significantly decreased apoptotic rates (P<0.05) were observed in the three- and six-week experimental groups, however, no significant decrease was observed in the middle-stage OA group. In the early-stage OA rats, the thickness of the cartilage layer, as well as the levels of proteoglycans and type II collagen fibers, in the six-week experimental group, were significantly higher compared with the control and three-week subgroups, and a decreased apoptotic rate was observed (P<0.05). In the six-week experimental middle-stage OA group, significant differences were observed in the content of proteoglycans and type II collagen

  5. Effect of passive motion on articular cartilage in rat osteoarthritis.

    PubMed

    Qian, Jie; Liang, Jun; Wang, Yubin; Wang, Huifang

    2014-08-01

    The aim of the present study was to investigate the effect of moderate passive motion on articular cartilage in osteoarthritis (OA) caused by knee fracture. Sprague-Dawley rats (age, 8 weeks) with knee fractures were used to construct rat knee early- and middle-stage OA models. The stages were fixed for three and six weeks, with 20 rats analyzed at each stage. The experimental groups were exercised daily for 15 m/min with a specified duration. Following the completion of exercise, the effects of proper passive motion on cartilage thickness, the Mankin rating, cartilage collagen matrix, proteoglycan content and the morphological structure of the cartilage in the rat OA models were measured at the various degenerative stages caused by knee fracture. The proteoglycan content of the cartilage matrix, type II collagen fibers and the number of cartilage cells undergoing apoptosis were semiquantified. For early- and middle-stage OA, the cartilage layers in the three- or six-week experimental groups were significantly thicker and the levels of proteoglycans and type II collagen fibers in the weight-bearing area of the cartilage were significantly higher when compared with the control groups (P<0.05). In addition, the Mankin ratings were lower and ligament tension was increased when compared with the control group (P<0.05). In the early-stage OA group, significantly decreased apoptotic rates (P<0.05) were observed in the three- and six-week experimental groups, however, no significant decrease was observed in the middle-stage OA group. In the early-stage OA rats, the thickness of the cartilage layer, as well as the levels of proteoglycans and type II collagen fibers, in the six-week experimental group, were significantly higher compared with the control and three-week subgroups, and a decreased apoptotic rate was observed (P<0.05). In the six-week experimental middle-stage OA group, significant differences were observed in the content of proteoglycans and type II collagen

  6. Imaging of articular cartilage: current concepts

    PubMed Central

    RONGA, MARIO; ANGERETTI, GLORIA; FERRARO, SERGIO; DE FALCO, GIOVANNI; GENOVESE, EUGENIO A.; CHERUBINO, PAOLO

    2014-01-01

    Magnetic resonance imaging (MRI) is the gold standard method for non-invasive assessment of joint cartilage, providing information on the structure, morphology and molecular composition of this tissue. There are certain minimum requirements for a MRI study of cartilage tissue: machines with a high magnetic field (> 1.5 Tesla); the use of surface coils; and the use of T2-weighted, proton density-weighted fast-spin echo (T2 FSE-DP) and 3D fat-suppressed T1-weighted gradient echo (3D-FS T1W GRE) sequences. For better contrast between the different joint structures, MR arthography is a method that can highlight minimal fibrillation or fractures of the articular surface and allow evaluation of the integrity of the native cartilage-repair tissue interface. To assess the biochemical composition of cartilage and cartilage repair tissue, various techniques have been proposed for studying proteoglycans [dGEMRIC, T1rho mapping, sodium (23Na) imaging MRI, etc.], collagen, and water distribution [T2 mapping, “magnetisation transfer contrast”, diffusion-weighted imaging (DWI), and so on]. Several MRI classifications have been proposed for evaluating the processes of joint degeneration (WORMS, BLOKS, ICRS) and post-surgical maturation of repair tissue (MOCART, 3D MOCART). In the future, isotropic 3D sequences set to improve image quality and facilitate the diagnosis of disorders of articular structures adjacent to cartilage. PMID:25606557

  7. Preliminary investigation of intrinsic UV fluorescence spectroscopic changes associated with proteolytic digestion of bovine articular cartilage

    NASA Astrophysics Data System (ADS)

    Lewis, William; Padilla-Martinez, Juan-Pablo; Ortega-Martinez, Antonio; Franco, Walfre

    2016-03-01

    Degradation and destruction of articular cartilage is the etiology of osteoarthritis (OA), an entity second only to cardiovascular disease as a cause of disability in the United States. Joint mechanics and cartilage biochemistry are believed to play a role in OA; an optical tool to detect structural and chemical changes in articular cartilage might offer benefit for its early detection and treatment. The objective of the present study was to identify the spectral changes in intrinsic ultraviolet (UV) fluorescence of cartilage that occur after proteolytic digestion of cartilage. Bovine articular cartilage samples were incubated in varying concentrations of collagenase ranging from 10ug/mL up to 5mg/mL for 18 hours at 37°C, a model of OA. Pre- and post-incubation measurements were taken of the UV excitation-emission spectrum of each cartilage sample. Mechanical tests were performed to determine the pre- and post-digestion force/displacement ratio associated with indentation of each sample. Spectral changes in intrinsic cartilage fluorescence and stiffness of the cartilage were associated with proteolytic digestion. In particular, changes in the relative intensity of fluorescence peaks associated with pentosidine crosslinks (330 nm excitation, 390 nm emission) and tryptophan (290 nm excitation, 340 nm emission) were found to correlate with different degrees of cartilage digestion and cartilage stiffness. In principle, it may be possible to use UV fluorescence spectral data for early detection of damage to articular cartilage, and as a surrogate measure for cartilage stiffness.

  8. Resurfacing Damaged Articular Cartilage to Restore Compressive Properties

    PubMed Central

    Grenier, Stephanie; Donnelly, Patrick E.; Gittens, Jamila; Torzilli, Peter A.

    2014-01-01

    Surface damage to articular cartilage is recognized as the initial underlying process causing the loss of mechanical function in early-stage osteoarthritis. In this study, we developed structure-modifying treatments to potentially prevent, stabilize or reverse the loss in mechanical function. Various polymers (chondroitin sulfate, carboxymethylcellulose, sodium hyaluronate) and photoinitiators (riboflavin, irgacure 2959) were applied to the surface of collagenase-degraded cartilage and crosslinked in situ using UV light irradiation. While matrix permeability and deformation significantly increased following collagenase-induced degradation of the superficial zone, resurfacing using tyramine-substituted sodium hyaluronate and riboflavin decreased both values to a level comparable to that of intact cartilage. Repetitive loading of resurfaced cartilage showed minimal variation in the mechanical response over a 7 day period. Cartilage resurfaced using a low concentration of riboflavin had viable cells in all zones while a higher concentration resulted in a thin layer of cell death in the uppermost superficial zone. Our approach to repair surface damage initiates a new therapeutic advance in the treatment of injured articular cartilage with potential benefits that include enhanced mechanical properties, reduced susceptibility to enzymatic degradation and reduced adhesion of macrophages. PMID:25468298

  9. 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

  10. Techniques and applications of in vivo diffusion imaging of articular cartilage.

    PubMed

    Raya, José G

    2015-06-01

    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 and to the collagen architecture through the fractional anisotropy. However, the acquisition of DTI of articular cartilage in vivo is challenging due to the short T2 of articular cartilage (∼40 ms at 3 Tesla) 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

  11. 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

  12. Autophagy modulates articular cartilage vesicle formation in primary articular chondrocytes.

    PubMed

    Rosenthal, Ann K; Gohr, Claudia M; Mitton-Fitzgerald, Elizabeth; Grewal, Rupinder; Ninomiya, James; Coyne, Carolyn B; Jackson, William T

    2015-05-22

    Chondrocyte-derived extracellular organelles known as articular cartilage vesicles (ACVs) participate in non-classical protein secretion, intercellular communication, and pathologic calcification. Factors affecting ACV formation and release remain poorly characterized; although in some cell types, the generation of extracellular vesicles is associated with up-regulation of autophagy. We sought to determine the role of autophagy in ACV production by primary articular chondrocytes. Using an innovative dynamic model with a light scatter nanoparticle counting apparatus, we determined the effects of autophagy modulators on ACV number and content in conditioned medium from normal adult porcine and human osteoarthritic chondrocytes. Healthy articular chondrocytes release ACVs into conditioned medium and show significant levels of ongoing autophagy. Rapamycin, which promotes autophagy, increased ACV numbers in a dose- and time-dependent manner associated with increased levels of autophagy markers and autophagosome formation. These effects were suppressed by pharmacologic autophagy inhibitors and short interfering RNA for ATG5. Caspase-3 inhibition and a Rho/ROCK inhibitor prevented rapamycin-induced increases in ACV number. Osteoarthritic chondrocytes, which are deficient in autophagy, did not increase ACV number in response to rapamycin. SMER28, which induces autophagy via an mTOR-independent mechanism, also increased ACV number. ACVs induced under all conditions had similar ecto-enzyme specific activities and types of RNA, and all ACVs contained LC3, an autophagosome-resident protein. These findings identify autophagy as a critical participant in ACV formation, and augment our understanding of ACVs in cartilage disease and repair. PMID:25869133

  13. Quantitative proteomic profiling of human articular cartilage degradation in osteoarthritis.

    PubMed

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

    2014-12-01

    Osteoarthritis (OA) is the most common rheumatic pathology and is characterized primarily by articular cartilage degradation. Despite its high prevalence, there is no effective therapy to slow disease progression or regenerate the damaged tissue. Therefore, new diagnostic and monitoring tests for OA are urgently needed, which would also promote the development of alternative therapeutic strategies. In the present study, we have performed an iTRAQ-based quantitative proteomic analysis of secretomes from healthy human articular cartilage explants, comparing their protein profile to those from unwounded (early disease) and wounded (advanced disease) zones of osteoarthritic tissue. This strategy allowed us to identify a panel of 76 proteins that are distinctively released by the diseased tissue. Clustering analysis allowed the classification of proteins according to their different profile of release from cartilage. Among these proteins, the altered release of osteoprotegerin (decreased in OA) and periostin (increased in OA), both involved in bone remodelling processes, was verified in further analyses. Moreover, periostin was also increased in the synovial fluid of OA patients. Altogether, the present work provides a novel insight into the mechanisms of human cartilage degradation and a number of new cartilage-characteristic proteins with possible biomarker value for early diagnosis and prognosis of OA. PMID:25383958

  14. Articular cartilage: from formation to tissue engineering.

    PubMed

    Camarero-Espinosa, Sandra; Rothen-Rutishauser, Barbara; Foster, E Johan; Weder, Christoph

    2016-05-26

    Hyaline cartilage is the nonlinear, inhomogeneous, anisotropic, poro-viscoelastic connective tissue that serves as friction-reducing and load-bearing cushion in synovial joints and is vital for mammalian skeletal movements. Due to its avascular nature, low cell density, low proliferative activity and the tendency of chondrocytes to de-differentiate, cartilage cannot regenerate after injury, wear and tear, or degeneration through common diseases such as osteoarthritis. Therefore severe damage usually requires surgical intervention. Current clinical strategies to generate new tissue include debridement, microfracture, autologous chondrocyte transplantation, and mosaicplasty. While articular cartilage was predicted to be one of the first tissues to be successfully engineered, it proved to be challenging to reproduce the complex architecture and biomechanical properties of the native tissue. Despite significant research efforts, only a limited number of studies have evolved up to the clinical trial stage. This review article summarizes the current state of cartilage tissue engineering in the context of relevant biological aspects, such as the formation and growth of hyaline cartilage, its composition, structure and biomechanical properties. Special attention is given to materials development, scaffold designs, fabrication methods, and template-cell interactions, which are of great importance to the structure and functionality of the engineered tissue. PMID:26923076

  15. Damage Control Mechanisms in Articular Cartilage

    PubMed Central

    Martin, James A; Scherb, MB; Lembke, Lois A; Buckwalter, Joseph

    2000-01-01

    Articular chondrocytes maintain cartilage throughout life by replacing lost or damaged matrix with freshly synthesized material. Synthesis activity is regulated, rapidly increasing to well above basal levels in response to cartilage injury. Such responses suggest that synthesis activity is linked to the rate of matrix loss by endogenous "damage control" mechanisms. As a major stimulator of matrix synthesis in cartilage, insulin-like growth factor I (IGF-I) is likely to play a role in such mechanisms. Although IGF-I is nearly ubiquitous, its bioavailability in cartilage is controlled by IGF-I binding proteins (IGFBPs) secreted by chondrocytes. IGFBPs are part of a complex system, termed the IGF-I axis, that tightly regulates IGF-I activities. For the most part, IGFBPs block IGF-I activity by sequestering IGF-I from its cell surface receptor. We recently found that the expression of one binding protein, IGFBP-3, increases with chondrocyte age, paralleling an age-related decline in synthesis activity. In addition, IGFBP-3 is overexpressed in osteoarthritic cartilage, leading to metabolic disturbances that contribute to cartilage degeneration. These observations indicate that IGFBP-3 plays a crucial role in regulating matrix synthesis in cartilage, and suggest that cartilage damage control mechanisms may fail due to age-related changes in IGFBP-3 expression or distribution. Our investigation of this hypothesis began with immunolocalization studies to determine the tissue distribution of IGFBP-3 in human cartilage. We found that IGFBP-3 accumulated around chondrocytes in the pericellular/territorial matrix, where it co-localized with fibronectin, but not with the other matrix proteins tenascin-C and type VI collagen. This result suggested that the IGFBP-3 distribution is determined by binding to fibronectin. Binding studies using purified proteins demonstrated that IGFBP-3 does in fact bind to fibronectin, but not to tenascin-C or type VI collagen. Finally, we

  16. Minced articular cartilage--basic science, surgical technique, and clinical application.

    PubMed

    McCormick, Frank; Yanke, Adam; Provencher, Matthew T; Cole, Brian J

    2008-12-01

    Minced articular cartilage procedures are attractive surgical approaches for repairing articular cartilage, as they are 1-staged, autologous, and inserted on a carrier that can potentially be placed arthroscopically. The principle of mincing the autologous donor cartilage is to create a larger surface area for cartilage expansion. Placement on a scaffold carrier allows for a chondro-inductive and chondro-conductive milieu. Early animal and preclinical models have demonstrated hyaline-like tissue repair. Further work needs to be conducted in this promising approach. PMID:19011553

  17. Radiography of rabbit articular cartilage with diffraction-enhanced imaging.

    PubMed

    Muehleman, Carol; Chapman, L Dean; Kuettner, Klaus E; Rieff, Joel; Mollenhauer, Juergen A; Massuda, Koichi; Zhong, Zhong

    2003-05-01

    Articular cartilage of synovial joints is not visible with conventional X-ray imaging. Hence, the gradual degeneration and destruction of articular cartilage, which is characteristic of degenerative joint diseases, is only detected at a late stage when the cartilage is lost and the joint space that it once occupied narrows. The development of an X-ray imaging technique that could detect both the degenerative cartilage and bone features of joint diseases is of special interest. Here we show, for the first time, that a high-contrast imaging technique, diffraction-enhanced X-ray imaging (DEI), allows the visualization of articular cartilage of both disarticulated and articulated rabbit knee joints. Furthermore, a single cartilage lesion can be visualized within an intact joint. The results suggest that DEI has the potential to be of use in the study of cartilage degeneration. PMID:12704696

  18. Follistatin Alleviates Synovitis and Articular Cartilage Degeneration Induced by Carrageenan

    PubMed Central

    Yamada, Jun; Abula, Kahaer; Inoue, Makiko; Sekiya, Ichiro; Muneta, Takeshi

    2014-01-01

    Activins are proinflammatory cytokines which belong to the TGFβ superfamily. Follistatin is an extracellular decoy receptor for activins. Since both activins and follistatin are expressed in articular cartilage, we hypothesized that activin-follistatin signaling participates in the process of joint inflammation and cartilage degeneration. To test this hypothesis, we examined the effects of follistatin in a carrageenan-induced mouse arthritis model. Synovitis induced by intra-articular injection of carrageenan was significantly alleviated by preinjection with follistatin. Macrophage infiltration into the synovial membrane was significantly reduced in the presence of follistatin. In addition, follistatin inhibited proteoglycan erosion induced by carrageenan in articular cartilage. These data indicate that activin-follistatin signaling is involved in joint inflammation and cartilage homeostasis. Our data suggest that follistatin can be a new therapeutic target for inflammation-induced articular cartilage degeneration. PMID:25574420

  19. Simultaneous magnetic resonance imaging and consolidation measurement of articular cartilage.

    PubMed

    Wellard, Robert Mark; Ravasio, Jean-Philippe; Guesne, Samuel; Bell, Christopher; Oloyede, Adekunle; Tevelen, Greg; Pope, James M; Momot, Konstantin I

    2014-01-01

    Magnetic resonance imaging (MRI) offers the opportunity to study biological tissues and processes in a non-disruptive manner. The technique shows promise for the study of the load-bearing performance (consolidation) of articular cartilage and changes in articular cartilage accompanying osteoarthritis. Consolidation of articular cartilage involves the recording of two transient characteristics: the change over time of strain and the hydrostatic excess pore pressure (HEPP). MRI study of cartilage consolidation under mechanical load is limited by difficulties in measuring the HEPP in the presence of the strong magnetic fields associated with the MRI technique. Here we describe the use of MRI to image and characterize bovine articular cartilage deforming under load in an MRI compatible consolidometer while monitoring pressure with a Fabry-Perot interferometer-based fiber-optic pressure transducer. PMID:24803188

  20. Tissue Engineering of Articular Cartilage with Biomimetic Zones

    PubMed Central

    Klein, Travis J.; Malda, Jos; Sah, Robert L.

    2009-01-01

    Articular cartilage damage is a persistent and increasing problem with the aging population, and treatments to achieve biological repair or restoration remain a challenge. Cartilage tissue engineering approaches have been investigated for over 20 years, but have yet to achieve the consistency and effectiveness for widespread clinical use. One of the potential reasons for this is that the engineered tissues do not have or establish the normal zonal organization of cells and extracellular matrix that appears critical for normal tissue function. A number of approaches are being taken currently to engineer tissue that more closely mimics the organization of native articular cartilage. This review focuses on the zonal organization of native articular cartilage, strategies being used to develop such organization, the reorganization that occurs after culture or implantation, and future prospects for the tissue engineering of articular cartilage with biomimetic zones. PMID:19203206

  1. Simultaneous Magnetic Resonance Imaging and Consolidation Measurement of Articular Cartilage

    PubMed Central

    Wellard, Robert Mark; Ravasio, Jean-Philippe; Guesne, Samuel; Bell, Christopher; Oloyede, Adekunle; Tevelen, Greg; Pope, James M.; Momot, Konstantin I.

    2014-01-01

    Magnetic resonance imaging (MRI) offers the opportunity to study biological tissues and processes in a non-disruptive manner. The technique shows promise for the study of the load-bearing performance (consolidation) of articular cartilage and changes in articular cartilage accompanying osteoarthritis. Consolidation of articular cartilage involves the recording of two transient characteristics: the change over time of strain and the hydrostatic excess pore pressure (HEPP). MRI study of cartilage consolidation under mechanical load is limited by difficulties in measuring the HEPP in the presence of the strong magnetic fields associated with the MRI technique. Here we describe the use of MRI to image and characterize bovine articular cartilage deforming under load in an MRI compatible consolidometer while monitoring pressure with a Fabry-Perot interferometer-based fiber-optic pressure transducer. PMID:24803188

  2. Diffusion coefficients of articular cartilage for different CT and MRI contrast agents.

    PubMed

    Kulmala, K A M; Korhonen, R K; Julkunen, P; Jurvelin, J S; Quinn, T M; Kröger, H; Töyräs, J

    2010-10-01

    In contrast enhanced magnetic resonance imaging (MRI) and computed tomography (CT), the equilibrium distribution of anionic contrast agent is expected to reflect the fixed charged density (FCD) of articular cartilage. Diffusion is mainly responsible for the transport of contrast agents into cartilage. In osteoarthritis, cartilage composition changes at early stages of disease, and solute diffusion is most likely affected. Thus, investigation of contrast agent diffusion could enable new methods for imaging of cartilage composition. The aim of this study was to determine the diffusion coefficient of four contrast agents (ioxaglate, gadopentetate, iodide, gadodiamide) in bovine articular cartilage. The contrast agents were different in molecular size and charge. In peripheral quantitative CT experiments, penetration of contrast agent into the tissue was allowed either through the articular surface or through deep cartilage. To determine diffusion coefficients, a finite element model based on Fick's law was fitted to experimental data. Diffusion through articular surface was faster than through deep cartilage with every contrast agent. Iodide, being of atomic size, diffused into the cartilage significantly faster (q<0.05) than the other three contrast agents, for either transport direction. The diffusion coefficients of all clinical contrast agents (ioxaglate, gadopentetate and gadodiamide) were relatively low (142.8-253.7 μm(2)/s). In clinical diagnostics, such slow diffusion may not reach equilibrium and this jeopardizes the determination of FCD by standard methods. However, differences between diffusion through articular surface and deep cartilage, that are characterized by different tissue composition, suggest that diffusion coefficients may correlate with cartilage composition. Present method could therefore enable image-based assessment of cartilage composition by determination of diffusion coefficients within cartilage tissue. PMID:20594900

  3. Remobilization does not fully restore immobilization induced articular cartilage atrophy.

    PubMed

    Haapala, J; Arokoski, J P; Hyttinen, M M; Lammi, M; Tammi, M; Kovanen, V; Helminen, H J; Kiviranta, I

    1999-05-01

    The recovery of articular cartilage from immobilization induced atrophy was studied. The right hind limbs of 29-week-old beagle dogs were immobilized for 11 weeks and then remobilized for 50 weeks. Cartilage from the immobilized knee was compared with tissue from age matched control animals. After the immobilization period, uncalcified articular cartilage glycosaminoglycan concentration was reduced by 20% to 23%, the reduction being largest (44%) in the superficial zone. The collagen fibril network showed no significant changes, but the amount of collagen crosslinks was reduced (13.5%) during immobilization. After remobilization, glycosaminoglycan concentration was restored at most sites, except for in the upper parts of uncalcified cartilage in the medial femoral and tibial condyles (9% to 17% less glycosaminoglycans than in controls). The incorporation of 35SO4 was not changed, and remobilization also did not alter the birefringence of collagen fibrils. Remobilization restored the proportion of collagen crosslinks to the control level. The changes induced by joint unloading were reversible at most sites investigated, but full restoration of articular cartilage glycosaminoglycan concentration was not obtained in all sites, even after remobilization for 50 weeks. This suggests that lengthy immobilization of a joint can cause long lasting articular cartilage proteoglycan alterations at the same time as collagen organization remains largely unchanged. Because proteoglycans exert strong influence on the biomechanical properties of cartilage, lengthy immobilization may jeopardize the well being of articular cartilage. PMID:10335301

  4. Extraction of mechanical properties of articular cartilage from osmotic swelling behavior monitored using high frequency ultrasound.

    PubMed

    Wang, Q; Zheng, Y P; Niu, H J; Mak, A F T

    2007-06-01

    Articular cartilage is a biological weight-bearing tissue covering the bony ends of articulating joints. Negatively charged proteoglycan (PG) in articular cartilage is one of the main factors that govern its compressive mechanical behavior and swelling phenomenon. PG is nonuniformly distributed throughout the depth direction, and its amount or distribution may change in the degenerated articular cartilage such as osteoarthritis. In this paper, we used a 50 MHz ultrasound system to study the depth-dependent strain of articular cartilage under the osmotic loading induced by the decrease of the bathing saline concentration. The swelling-induced strains under the osmotic loading were used to determine the layered material properties of articular cartilage based on a triphasic model of the free-swelling. Fourteen cylindrical cartilage-bone samples prepared from fresh normal bovine patellae were tested in situ in this study. A layered triphasic model was proposed to describe the depth distribution of the swelling strain for the cartilage and to determine its aggregate modulus H(a) at two different layers, within which H(a) was assumed to be linearly dependent on the depth. The results showed that H(a) was 3.0+/-3.2, 7.0+/-7.4, 24.5+/-11.1 MPa at the cartilage surface, layer interface, and deep region, respectively. They are significantly different (p<0.01). The layer interface located at 70%+/-20% of the overall thickness from the uncalcified-calcified cartilage interface. Parametric analysis demonstrated that the depth-dependent distribution of the water fraction had a significant effect on the modeling results but not the fixed charge density. This study showed that high-frequency ultrasound measurement together with triphasic modeling is practical for quantifying the layered mechanical properties of articular cartilage nondestructively and has the potential for providing useful information for the detection of the early signs of osteoarthritis. PMID:17536909

  5. Alterations in periarticular bone and cross talk between subchondral bone and articular cartilage in osteoarthritis.

    PubMed

    Goldring, Steven R

    2012-08-01

    The articular cartilage and the subchondral bone form a biocomposite that is uniquely adapted to the transfer of loads across the diarthrodial joint. During the evolution of the osteoarthritic process biomechanical and biological processes result in alterations in the composition, structure and functional properties of these tissues. Given the intimate contact between the cartilage and bone, alterations of either tissue will modulate the properties and function of the other joint component. The changes in periarticular bone tend to occur very early in the development of OA. Although chondrocytes also have the capacity to modulate their functional state in response to loading, the capacity of these cells to repair and modify their surrounding extracellular matrix is relatively limited in comparison to the adjacent subchondral bone. This differential adaptive capacity likely underlies the more rapid appearance of detectable skeletal changes in OA in comparison to the articular cartilage. The OA changes in periarticular bone include increases in subchondral cortical bone thickness, gradual decreases in subchondral trabeular bone mass, formation of marginal joint osteophytes, development of bone cysts and advancement of the zone of calcified cartilage between the articular cartilage and subchondral bone. The expansion of the zone of calcified cartilage contributes to overall thinning of the articular cartilage. The mechanisms involved in this process include the release of soluble mediators from chondrocytes in the deep zones of the articular cartilage and/or the influences of microcracks that have initiated focal remodeling in the calcified cartilage and subchondral bone in an attempt to repair the microdamage. There is the need for further studies to define the pathophysiological mechanisms involved in the interaction between subchondral bone and articular cartilage and for applying this information to the development of therapeutic interventions to improve the

  6. A literature review of lasers and articular cartilage.

    PubMed

    Vangsness, C T; Ghaderi, B

    1993-05-01

    Articles from the English literature concerning lasers and articular cartilage were reviewed. Different experimental methods and laser systems were analyzed. Many studies lacked scientific validity. Future investigations with sound biologic foundations are recommended. PMID:8327386

  7. 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

  8. Evaluation of correlation of articular cartilage staining for DDR2 and proteoglycans with histological tissue damage and the results of radiographic assessment in patients with early stages of knee osteoarthritis

    PubMed Central

    Suutre, Siim; Kerna, Irina; Lintrop, Mare; Tamm, Hannes; Aunapuu, Marina; Arend, Andres; Tamm, Agu

    2015-01-01

    Objective: To determine, if staining of articular cartilage for proteoglycans (natural element of healthy and functioning cartilage) and discoidin domain receptor 2 (DDR2) (a protein associated with articular cartilage degradation) is correlated with histological tissue damage or radiographic assessment score in patients with early stages of knee osteoarthritis (OA). Method: 40 patients, with early stage OA were enrolled, from whom the biopsies for histological and immunohistochemical studies were obtained from edge of the femoral condyle during the arthroscopy. Semi-quantitative computer based analysis was used to evaluate the proportion of staining in histological sections. Results: No correlation was shown between the proportion of tissue stained for DDR2 and histological score or the results of radiographic assessment of tibiofemoral (TF) joint. There was a negative correlation between the proportion of tissue stained for DDR2 and radiographic grade of patellofemoral (PF) OA (Spearman r=-0.34; 95% CI -0.60 to -0.02; P=0.03). No correlation was shown between the proportion of tissue stained for proteoglycans and histological score or the results of radiographic assessment of TF and PF joints. A negative correlation was found between proportion of tissue stained for DDR2 and proteoglycans. Spearman r=-0.43; 95% CI=-0.66 to -0.12; P=0.006. Conclusion: Production of DDR2 in articular cartilage could be related to early stages of OA, as it is significantly correlated to decrease of staining for cartilage proteoglycans. The role of production of DDR2 in cartilage may be decreased in stages, where higher grades of OA are detected on the radiographs. PMID:26191278

  9. The Functions of BMP3 in Rabbit Articular Cartilage Repair

    PubMed Central

    Zhang, Zhe; Yang, Wenyu; Cao, Yiting; Shi, Yanping; Lei, Chen; Du, Bo; Li, Xuemin; Zhang, Qiqing

    2015-01-01

    Bone morphogenetic proteins (BMPs) play important roles in skeletal development and repair. Previously, we found fibroblast growth factor 2 (FGF2) induced up-regulation of BMP2, 3, 4 in the process of rabbit articular cartilage repair, which resulted in satisfactory repair effects. As BMP2/4 show a clearly positive effect for cartilage repair, we investigated the functions of BMP3 in rabbit articular cartilage repair. In this paper, we find that BMP3 inhibits the repair of partial-thickness defect of articular cartilage in rabbit by inducing the degradation of extracellular matrix, interfering with the survival of chondrocytes surrounding the defect, and directly inhibiting the expression of BMP2 and BMP4. Meanwhile BMP3 suppress the repair of full-thickness cartilage defect by destroying the subchondral bone through modulating the proliferation and differentiation of bone marrow stem cells (BMSCs), and directly increasing the expression of BMP4. Although BMP3 has different functions in the repair of partial and full-thickness defects of articular cartilage in rabbit, the regulation of BMP expression is involved in both of them. Together with our previous findings, we suggest the regulation of the BMP signaling pathway by BMP3 is essential in articular cartilage repair. PMID:26528966

  10. The Functions of BMP3 in Rabbit Articular Cartilage Repair.

    PubMed

    Zhang, Zhe; Yang, Wenyu; Cao, Yiting; Shi, Yanping; Lei, Chen; Du, Bo; Li, Xuemin; Zhang, Qiqing

    2015-01-01

    Bone morphogenetic proteins (BMPs) play important roles in skeletal development and repair. Previously, we found fibroblast growth factor 2 (FGF2) induced up-regulation of BMP2, 3, 4 in the process of rabbit articular cartilage repair, which resulted in satisfactory repair effects. As BMP2/4 show a clearly positive effect for cartilage repair, we investigated the functions of BMP3 in rabbit articular cartilage repair. In this paper, we find that BMP3 inhibits the repair of partial-thickness defect of articular cartilage in rabbit by inducing the degradation of extracellular matrix, interfering with the survival of chondrocytes surrounding the defect, and directly inhibiting the expression of BMP2 and BMP4. Meanwhile BMP3 suppress the repair of full-thickness cartilage defect by destroying the subchondral bone through modulating the proliferation and differentiation of bone marrow stem cells (BMSCs), and directly increasing the expression of BMP4. Although BMP3 has different functions in the repair of partial and full-thickness defects of articular cartilage in rabbit, the regulation of BMP expression is involved in both of them. Together with our previous findings, we suggest the regulation of the BMP signaling pathway by BMP3 is essential in articular cartilage repair. PMID:26528966

  11. Leptin plays a catabolic role on articular cartilage.

    PubMed

    Bao, Jia-peng; Chen, Wei-ping; Feng, Jie; Hu, Peng-fei; Shi, Zhong-li; Wu, Li-dong

    2010-10-01

    Leptin has been shown to play a crucial role in the regulation of body weight. There is also evidence that this adipokine plays a key role in the process of osteoarthritis. However, the precise role of leptin on articular cartilage metabolism is not clear. We investigate the role of leptin on articular cartilage in vivo in this study. Recombinant rat leptin (100 μg) was injected into the knee joints of rats, 48 h later, messenger RNA (mRNA) expression and protein levels of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), matrix metalloproteinases 2 and 9 (MMP-2, MMP-9), cathepsin D, and collagen II from articular cartilage were analyzed by real-time quantitative polymerase chain reaction (PCR) and western blot. Two important aggrecanases ADAMTS-4 and -5 (a disintegrin and metalloproteinase with thrombospondin motifs 4 and 5) were also analyzed by real-time quantitative PCR. Besides, articular cartilage was also assessed for proteoglycan/GAG content by Safranin O staining. Leptin significantly increased both gene and protein levels of MMP-2, MMP-9, cathepsin D, and collagen II, while decreased bFGF markedly in cartilage. Moreover, the gene expression of ADAMTS-4 and -5 were markedly increased, and histologically assessed depletion of proteoglycan in articular cartilage was observed after treatment with leptin. These results strongly suggest that leptin plays a catabolic role on cartilage metabolism and may be a disadvantage factor involve in the pathological process of OA. PMID:19876764

  12. Directed differentiation of induced pluripotent stem cells into chondrogenic lineages for articular cartilage treatment

    PubMed Central

    Lach, Michał; Richter, Magdalena; Pawlicz, Jarosław; Suchorska, Wiktoria M

    2014-01-01

    In recent years, increases in the number of articular cartilage injuries caused by environmental factors or pathological conditions have led to a notable rise in the incidence of premature osteoarthritis. Osteoarthritis, considered a disease of civilization, is the leading cause of disability. At present, standard methods for treating damaged articular cartilage, including autologous chondrocyte implantation or microfracture, are short-term solutions with important side effects. Emerging treatments include the use of induced pluripotent stem cells, a technique that could provide a new tool for treatment of joint damage. However, research in this area is still early, and no optimal protocol for transforming induced pluripotent stem cells into chondrocytes has yet been established. Developments in our understanding of cartilage developmental biology, together with the use of modern technologies in the field of tissue engineering, provide an opportunity to create a complete functional model of articular cartilage. PMID:25383175

  13. Quantitative ultrasound imaging detects degenerative changes in articular cartilage surface and subchondral bone

    NASA Astrophysics Data System (ADS)

    Saarakkala, Simo; Laasanen, Mikko S.; Jurvelin, Jukka S.; Töyräs, Juha

    2006-10-01

    Previous studies have suggested that quantitative ultrasound imaging could sensitively diagnose degeneration of the articular surface and changes in the subchondral bone during the development of osteoarthrosis (OA). We have recently introduced a new parameter, ultrasound roughness index (URI), for the quantification of cartilage surface roughness, and successfully tested it with normal and experimentally degraded articular surfaces. In this in vitro study, the applicability of URI was tested in bovine cartilage samples with spontaneously developed tissue degeneration. Simultaneously, we studied the sensitivity of quantitative ultrasound imaging to detect degenerative changes in the cartilage-bone interface. For reference, histological degenerative grade of the cartilage samples was determined. Mechanical reference measurements were also conducted. Cartilage surface roughness (URI) was significantly (p < 0.05) higher in histologically degenerated samples with inferior mechanical properties. Ultrasound reflection at the cartilage-bone interface was also significantly (p < 0.05) increased in degenerated samples. Furthermore, it was quantitatively confirmed that ultrasound attenuation in the overlying cartilage significantly affects the measured ultrasound reflection values from the cartilage-bone interface. To conclude, the combined ultrasound measurement of the cartilage surface roughness and ultrasound reflection at the cartilage-bone interface complement each other, and may together enable more sensitive and quantitative diagnosis of early OA or follow up after surgical cartilage repair.

  14. Quantitative ultrasound imaging detects degenerative changes in articular cartilage surface and subchondral bone.

    PubMed

    Saarakkala, Simo; Laasanen, Mikko S; Jurvelin, Jukka S; Töyräs, Juha

    2006-10-21

    Previous studies have suggested that quantitative ultrasound imaging could sensitively diagnose degeneration of the articular surface and changes in the subchondral bone during the development of osteoarthrosis (OA). We have recently introduced a new parameter, ultrasound roughness index (URI), for the quantification of cartilage surface roughness, and successfully tested it with normal and experimentally degraded articular surfaces. In this in vitro study, the applicability of URI was tested in bovine cartilage samples with spontaneously developed tissue degeneration. Simultaneously, we studied the sensitivity of quantitative ultrasound imaging to detect degenerative changes in the cartilage-bone interface. For reference, histological degenerative grade of the cartilage samples was determined. Mechanical reference measurements were also conducted. Cartilage surface roughness (URI) was significantly (p<0.05) higher in histologically degenerated samples with inferior mechanical properties. Ultrasound reflection at the cartilage-bone interface was also significantly (p<0.05) increased in degenerated samples. Furthermore, it was quantitatively confirmed that ultrasound attenuation in the overlying cartilage significantly affects the measured ultrasound reflection values from the cartilage-bone interface. To conclude, the combined ultrasound measurement of the cartilage surface roughness and ultrasound reflection at the cartilage-bone interface complement each other, and may together enable more sensitive and quantitative diagnosis of early OA or follow up after surgical cartilage repair. PMID:17019042

  15. Multiscale Biofabrication of Articular Cartilage: Bioinspired and Biomimetic Approaches.

    PubMed

    Tatman, Philip David; Gerull, William; Sweeney-Easter, Sean; Davis, Jeffrey Isaac; Gee, Albert O; Kim, Deok-Ho

    2015-12-01

    Articular cartilage is the load-bearing tissue found inside all articulating joints of the body. It vastly reduces friction and allows for smooth gliding between contacting surfaces. The structure of articular cartilage matrix and cellular composition is zonal and is important for its mechanical properties. When cartilage becomes injured through trauma or disease, it has poor intrinsic healing capabilities. The spectrum of cartilage injury ranges from isolated areas of the joint to diffuse breakdown and the clinical appearance of osteoarthritis. Current clinical treatment options remain limited in their ability to restore cartilage to its normal functional state. This review focuses on the evolution of biomaterial scaffolds that have been used for functional cartilage tissue engineering. In particular, we highlight recent developments in multiscale biofabrication approaches attempting to recapitulate the complex 3D matrix of native articular cartilage tissue. Additionally, we focus on the application of these methods to engineering each zone of cartilage and engineering full-thickness osteochondral tissues for improved clinical implantation. These methods have shown the potential to control individual cell-to-scaffold interactions and drive progenitor cell differentiation into a chondrocyte lineage. The use of these bioinspired nanoengineered scaffolds hold promise for recreation of structure and function on the whole tissue level and may represent exciting new developments for future clinical applications for cartilage injury and restoration. PMID:26200439

  16. Delivering Agents Locally into Articular Cartilage by Intense MHz Ultrasound

    PubMed Central

    Nieminen, Heikki J.; Ylitalo, Tuomo; Suuronen, Jussi-Petteri; Rahunen, Krista; Salmi, Ari; Saarakkala, Simo; Serimaa, Ritva; Hæggström, Edward

    2015-01-01

    There is no cure for osteoarthritis. Current drug delivery relies on systemic delivery or injections into the joint. Because articular cartilage (AC) degeneration can be local and drug exposure outside the lesion can cause adverse effects, localized drug delivery could permit new drug treatment strategies. We investigated whether intense megahertz ultrasound (frequency: 1.138 MHz, peak positive pressure: 2.7 MPa, Ispta: 5 W/cm2, beam width: 5.7 mm at −6 dB, duty cycle: 5%, pulse repetition frequency: 285 Hz, mechanical index: 1.1) can deliver agents into AC without damaging it. Using ultrasound, we delivered a drug surrogate down to a depth corresponding to 53% depth of the AC thickness without causing histologically detectable damage to the AC. This may be important because early osteoarthritis typically exhibits histopathologic changes in the superficial AC. In conclusion, we identify intense megahertz ultrasound as a technique that potentially enables localized non-destructive delivery of osteoarthritis drugs or drug carriers into articular cartilage. PMID:25922135

  17. Three-dimensional collagen architecture in bovine articular cartilage.

    PubMed

    Jeffery, A K; Blunn, G W; Archer, C W; Bentley, G

    1991-09-01

    The three-dimensional architecture of bovine articular cartilage collagen and its relationship to split lines has been studied with scanning electron microscopy. In the middle and superficial zones, collagen was organised in a layered or leaf-like manner. The orientation was vertical in the intermediate zone, curving to become horizontal and parallel to the articular surface in the superficial zone. Each leaf consisted of a fine network of collagen fibrils. Adjacent leaves merged or were closely linked by bridging fibrils and were arranged according to the split-line pattern. The surface layer (lamina splendens) was morphologically distinct. Although ordered, the overall collagen structure was different in each plane (anisotropic) a property described in previous morphological and biophysical studies. As all components of the articular cartilage matrix interact closely, the three-dimensional organisation of collagen is important when considering cartilage function and the processes of cartilage growth, injury and repair. PMID:1894669

  18. Cryoprotectant kinetic analysis of a human articular cartilage vitrification protocol.

    PubMed

    Shardt, Nadia; Al-Abbasi, Khaled K; Yu, Hana; Jomha, Nadr M; McGann, Locksley E; Elliott, Janet A W

    2016-08-01

    We recently published a protocol to vitrify human articular cartilage and a method of cryoprotectant removal in preparation for transplantation. The current study's goal was to perform a cryoprotectant kinetic analysis and theoretically shorten the procedure used to vitrify human articular cartilage. First, the loading of the cryoprotectants was modeled using Fick's law of diffusion, and this information was used to predict the kinetics of cryoprotectant efflux after the cartilage sample had been warmed. We hypothesized that diffusion coefficients obtained from the permeation of individual cryoprotectants into porcine articular cartilage could be used to provide a reasonable prediction of the cryoprotectant loading and of the combined cryoprotectant efflux from vitrified human articular cartilage. We tested this hypothesis with experimental efflux measurements. Osteochondral dowels from three patients were vitrified, and after warming, the articular cartilage was immersed in 3 mL X-VIVO at 4 °C in two consecutive solutions, each for 24 h, with the solution osmolality recorded at various times. Measured equilibrium values agreed with theoretical values within a maximum of 15% for all three samples. The results showed that diffusion coefficients for individual cryoprotectants determined from experiments with 2-mm thick porcine cartilage can be used to approximate the rate of efflux of the combined cryoprotectants from vitrified human articular cartilage of similar thickness. Finally, Fick's law of diffusion was used in a computational optimization to shorten the protocol with the constraint of maintaining the theoretical minimum cryoprotectant concentration needed to achieve vitrification. The learning provided by this study will enable future improvements in tissue vitrification. PMID:27221520

  19. Mechanisms of disruption of the articular cartilage surface in inflammation. Neutrophil elastase increases availability of collagen type II epitopes for binding with antibody on the surface of articular cartilage.

    PubMed Central

    Jasin, H E; Taurog, J D

    1991-01-01

    cartilage, exposing epitopes on type II collagen. They also help clarify the pathogenic mechanisms involved in early articular cartilage damage in inflammatory joint diseases. PMID:1708782

  20. Thermal energy effects on articular cartilage: a multidisciplinary evaluation

    NASA Astrophysics Data System (ADS)

    Kaplan, Lee D.; Ernsthausen, John; Ionescu, Dan S.; Studer, Rebecca K.; Bradley, James P.; Chu, Constance R.; Fu, Freddie H.; Farkas, Daniel L.

    2002-05-01

    Partial thickness articular cartilage lesions are commonly encountered in orthopedic surgery. These lesions do not have the ability to heal by themselves, due to lack of vascular supply. Several types of treatment have addressed this problem, including mechanical debridement and thermal chondroplasty. The goal of these treatments is to provide a smooth cartilage surface and prevent propagation of the lesions. Early thermal chondroplasty was performed using lasers, and yielded very mixed results, including severe damage to the cartilage, due to poor control of the induced thermal effects. This led to the development (including commercial) of probes using radiofrequency to generate the thermal effects desired for chondroplasty. Similar concerns over the quantitative aspects and control ability of the induced thermal effects in these treatments led us to test the whole range of complex issues and parameters involved. Our investigations are designed to simultaneously evaluate clinical conditions, instrument variables for existing radiofrequency probes (pressure, speed, distance, dose) as well as the associated basic science issues such as damage temperature and controllability (down to the subcellular level), damage geometry, and effects of surrounding conditions (medium, temperature, flow, pressure). The overall goals of this work are (1) to establish whether thermal chondroplasty can be used in a safe and efficacious manner, and (2) provide a prescription for multi-variable optimization of the way treatments are delivered, based on quantitative analysis. The methods used form an interdisciplinary set, to include precise mechanical actuation, high accuracy temperature and temperature gradient control and measurement, advanced imaging approaches and mathematical modeling.

  1. 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

  2. Effects of Hyaluronic Acid and γ–Globulin Concentrations on the Frictional Response of Human Osteoarthritic Articular Cartilage

    PubMed Central

    Son, Kyeong-Min; Thompson, Mark S.; Park, Sungchan; Chang, Jun-Dong; Nam, Ju-Suk; Park, Seonghun; Lee, Sang-Soo

    2014-01-01

    Synovial fluid plays an important role in lubricating synovial joints. Its main constituents are hyaluronic acid (HA) and γ–globulin, acting as boundary lubricants for articular cartilage. The aim of the study was to demonstrate the concentration-dependent effect of HA and γ–globulin on the boundary-lubricating ability of human osteoarthritis (OA) cartilage. Normal, early and advance stage articular cartilage samples were obtained from human femoral heads and in presence of either HA or γ–globulin, cartilage frictional coefficient (µ) was measured by atomic force microscopy (AFM). In advanced stage OA, the cartilage superficial layer was observed to be completely removed and the damaged cartilage surface showed a higher µ value (∼0.409) than the normal cartilage surface (∼0.119) in PBS. Adsorbed HA and γ–globulin molecules significantly improved the frictional behavior of advanced OA cartilage, while they were ineffective for normal and early OA cartilage. In advanced-stage OA, the concentration-dependent frictional response of articular cartilage was observed with γ–globulin, but not with HA. Our result suggested that HA and γ–globulin may play a significant role in improving frictional behavior of advanced OA cartilage. During early-stage OA, though HA and γ–globulin had no effect on improving frictional behavior of cartilage, however, they might contribute to disease modifying effects of synovial fluid as observed in clinical settings. PMID:25426992

  3. 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.

  4. What can biophotonics tell us about the 3D microstructure of articular cartilage?

    PubMed

    Matcher, Stephen J

    2015-02-01

    Connective tissues such as articular cartilage have been the subject of study using novel optical techniques almost since the invention of polarized light microscopy (PLM). Early studies of polarized light micrographs were the main evidential basis for the establishment of quantitative models of articular cartilage collagen structure by Benninghoff and others. Even now, state of the art optical techniques including quantitative polarized light microscopy (qPLM), optical coherence tomography (OCT), polarization-sensitive optical coherence tomography (PS-OCT), second harmonic generation (SHG) microscopy, Fourier-transform infrared (FTIR) microscopy, Raman and optical hyperspectral reflectance and fluorescence imaging are providing new insights into articular cartilage structure from the nanoscale through to the mesoscale. New insights are promised by emerging modalities such as optical elastography. This short review highlights some key recent results from modern optical techniques. PMID:25694964

  5. What can biophotonics tell us about the 3D microstructure of articular cartilage?

    PubMed Central

    2015-01-01

    Connective tissues such as articular cartilage have been the subject of study using novel optical techniques almost since the invention of polarized light microscopy (PLM). Early studies of polarized light micrographs were the main evidential basis for the establishment of quantitative models of articular cartilage collagen structure by Benninghoff and others. Even now, state of the art optical techniques including quantitative polarized light microscopy (qPLM), optical coherence tomography (OCT), polarization-sensitive optical coherence tomography (PS-OCT), second harmonic generation (SHG) microscopy, Fourier-transform infrared (FTIR) microscopy, Raman and optical hyperspectral reflectance and fluorescence imaging are providing new insights into articular cartilage structure from the nanoscale through to the mesoscale. New insights are promised by emerging modalities such as optical elastography. This short review highlights some key recent results from modern optical techniques. PMID:25694964

  6. In-situ imaging of articular cartilage of the first carpometacarpal joint using co-registered optical coherence tomography and computed tomography

    NASA Astrophysics Data System (ADS)

    Cernohorsky, Paul; de Bruin, Daniel M.; van Herk, Marcel; Bras, Johannes; Faber, Dirk J.; Strackee, Simon D.; van Leeuwen, Ton G.

    2012-06-01

    Conventional imaging modalities are unable to depict the early degeneration of articular cartilage in osteoarthritis, especially in small joints. Optical coherence tomography has previously been used successfully in high-resolution imaging of cartilage tissue. This pilot cadaver study demonstrates the use of intra-articular optical coherence tomography in imaging of articular cartilage of the first carpometacarpal joint, producing high resolution images of the articular surface in which cartilage thickness and surface characteristics were assessed. Findings on optical coherence tomography were confirmed with histology. Furthermore, co-registration of optical coherence tomography and computed tomography was used to accurately determine the scanned trajectory and reconstruct a true-scale image overlay.

  7. New techniques in articular cartilage imaging.

    PubMed

    Potter, Hollis G; Black, Brandon R; Chong, Le Roy

    2009-01-01

    Standardized magnetic resonance imaging (MRI) pulse sequences provide an accurate, reproducible assessment of cartilage morphology. Three-dimensional (3D) modeling techniques enable semiautomated models of the joint surface and thickness measurements, which may eventually prove essential in templating before partial or total joint resurfacing as well as focal cartilage repair. Quantitative MRI techniques, such as T2 mapping, T1 rho, and delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), provide noninvasive information about cartilage and repair tissue biochemistry. Diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI) demonstrate information regarding the regional anisotropic variation of cartilage ultrastructure. Further research strengthening the association between quantitative MRI and cartilage material properties may predict the functional capacity of native and repaired tissue. MRI provides an essential objective assessment of cartilage regenerative procedures. PMID:19064167

  8. Inhibition of β-Catenin Signaling in Articular Chondrocytes Results in Articular Cartilage Destruction

    PubMed Central

    Zhu, Mei; Chen, Mo; Zuscik, Michael; Wu, Qiuqian; Wang, Yong-Jun; Rosier, Randy N.; O’Keefe, Regis J.; Chen, Di

    2009-01-01

    Objective Osteoarthritis is a degenerative joint disease whose molecular mechanism is currently unknown. Wnt/β-catenin signaling has been demonstrated to play a critical role in the development and function of articular chondrocytes. To determine the role of β-catenin signaling in articular chondrocyte function, we generated Col2a1-ICAT–transgenic mice to inhibit β-catenin signaling in chondrocytes. Methods The expression of the ICAT transgene was determined by immunostaining and Western blot analysis. Histologic analyses were performed to determine changes in articular cartilage structure and morphology. Cell apoptosis was determined by TUNEL staining and the immunostaining of cleaved caspase 3 and poly(ADP-ribose) polymerase (PARP) proteins. Expression of Bcl-2, Bcl-xL, and Bax proteins and caspase 9 and caspase 3/7 activities were examined in primary sternal chondrocytes isolated from 3-day-old neonatal Col2a1-ICAT–transgenic mice and their wild-type littermates and in primary chicken and porcine articular chondrocytes. Results Expression of the ICAT transgene was detected in articular chondrocytes of the transgenic mice. Associated with this, age-dependent articular cartilage destruction was observed in Col2a1-ICAT– transgenic mice. A significant increase in cell apoptosis in articular chondrocytes was identified by TUNEL staining and the immunostaining of cleaved caspase 3 and PARP proteins in these transgenic mice. Consistent with this, Bcl-2 and Bcl-xL expression were decreased and caspase 9 and caspase 3/7 activity were increased, suggesting that increased cell apoptosis may contribute significantly to the articular cartilage destruction observed in Col2a1-ICAT–transgenic mice. Conclusion Inhibition of β-catenin signaling in articular chondrocytes causes increased cell apoptosis and articular cartilage destruction in Col2a1-ICAT–transgenic mice. PMID:18576323

  9. Combinatorial scaffold morphologies for zonal articular cartilage engineering.

    PubMed

    Steele, J A M; McCullen, S D; Callanan, A; Autefage, H; Accardi, M A; Dini, D; Stevens, M M

    2014-05-01

    Articular cartilage lesions are a particular challenge for regenerative medicine strategies as cartilage function stems from a complex depth-dependent organization. Tissue engineering scaffolds that vary in morphology and function offer a template for zone-specific cartilage extracellular matrix (ECM) production and mechanical properties. We fabricated multi-zone cartilage scaffolds by the electrostatic deposition of polymer microfibres onto particulate-templated scaffolds produced with 0.03 or 1.0mm(3) porogens. The scaffolds allowed ample space for chondrocyte ECM production within the bulk while also mimicking the structural organization and functional interface of cartilage's superficial zone. Addition of aligned fibre membranes enhanced the mechanical and surface properties of particulate-templated scaffolds. Zonal analysis of scaffolds demonstrated region-specific variations in chondrocyte number, sulfated GAG-rich ECM, and chondrocytic gene expression. Specifically, smaller porogens (0.03mm(3)) yielded significantly higher sGAG accumulation and aggrecan gene expression. Our results demonstrate that bilayered scaffolds mimic some key structural characteristics of native cartilage, support in vitro cartilage formation, and have superior features to homogeneous particulate-templated scaffolds. We propose that these scaffolds offer promise for regenerative medicine strategies to repair articular cartilage lesions. PMID:24370641

  10. BMP Receptor Signaling Is Required for Postnatal Maintenance of Articular Cartilage

    PubMed Central

    2004-01-01

    Articular cartilage plays an essential role in health and mobility, but is frequently damaged or lost in millions of people that develop arthritis. The molecular mechanisms that create and maintain this thin layer of cartilage that covers the surface of bones in joint regions are poorly understood, in part because tools to manipulate gene expression specifically in this tissue have not been available. Here we use regulatory information from the mouse Gdf5 gene (a bone morphogenetic protein [BMP] family member) to develop new mouse lines that can be used to either activate or inactivate genes specifically in developing joints. Expression of Cre recombinase from Gdf5 bacterial artificial chromosome clones leads to specific activation or inactivation of floxed target genes in developing joints, including early joint interzones, adult articular cartilage, and the joint capsule. We have used this system to test the role of BMP receptor signaling in joint development. Mice with null mutations in Bmpr1a are known to die early in embryogenesis with multiple defects. However, combining a floxed Bmpr1a allele with the Gdf5-Cre driver bypasses this embryonic lethality, and leads to birth and postnatal development of mice missing the Bmpr1a gene in articular regions. Most joints in the body form normally in the absence of Bmpr1a receptor function. However, articular cartilage within the joints gradually wears away in receptor-deficient mice after birth in a process resembling human osteoarthritis. Gdf5-Cre mice provide a general system that can be used to test the role of genes in articular regions. BMP receptor signaling is required not only for early development and creation of multiple tissues, but also for ongoing maintenance of articular cartilage after birth. Genetic variation in the strength of BMP receptor signaling may be an important risk factor in human osteoarthritis, and treatments that mimic or augment BMP receptor signaling should be investigated as a possible

  11. Mechanical properties of normal and osteoarthritic human articular cartilage.

    PubMed

    Robinson, Dale L; Kersh, Mariana E; Walsh, Nicole C; Ackland, David C; de Steiger, Richard N; Pandy, Marcus G

    2016-08-01

    Isotropic hyperelastic models have been used to determine the material properties of normal human cartilage, but there remains an incomplete understanding of how these properties may be altered by osteoarthritis. The aims of this study were to (1) measure the material constants of normal and osteoarthritic human knee cartilage using isotropic hyperelastic models; (2) determine whether the material constants correlate with histological measures of structure and/or cartilage tissue damage; and (3) quantify the abilities of two common isotropic hyperelastic material models, the neo-Hookean and Yeoh models, to describe articular cartilage contact force, area, and pressure. Small osteochondral specimens of normal and osteoarthritic condition were retrieved from human cadaveric knees and from the knees of patients undergoing total knee arthroplasty and tested in unconfined compression at loading rates and large strains representative of weight-bearing activity. Articular surface contact area and lateral deformation were measured concurrently and specimen-specific finite element models then were used to determine the hyperelastic material constants. Structural parameters were measured using histological techniques while the severity of cartilage damage was quantified using the OARSI grading scale. The hyperelastic material constants correlated significantly with OARSI grade, indicating that the mechanical properties of cartilage for large strains change with tissue damage. The measurements of contact area described anisotropy of the tissue constituting the superficial zone. The Yeoh model described contact force and pressure more accurately than the neo-Hookean model, whereas both models under-predicted contact area and poorly described the anisotropy of cartilage within the superficial zone. These results identify the limits by which isotropic hyperelastic material models may be used to describe cartilage contact variables. This study provides novel data for the

  12. Studies on cathepsin B in human articular cartilage.

    PubMed Central

    Bayliss, M T; Ali, S Y

    1978-01-01

    The thiol proteinase cathepsin B (EC 3.4.22.1), previously called cathepsin B1, was assayed in human articular cartilage by its hydrolysis of the synthetic substrate alpha-N-benzoyl-DL-arginine 2-naphthylamide. The enzyme was activated by cysteine and EDTA and completely inhibited by iodoacetamide and HgCl2. It was also partially inhibited by whole human serum. Human osteoarthrotic cartilage had increased activity when compared with normal cartilage. Cathepsin B activity of normal cartilage was age-related, being high in juveniles and declining to low values in adult and elderly individuals. Cathepsin D and cathepsin B both exhibited a zonal variation through the cartilage depth; the surface cells appeared to contain more activity than those close to the subchondral bone. PMID:417724

  13. Quantitative MRI Evaluation of Articular Cartilage Using T2 Mapping Following Hip Arthroscopy for Femoroacetabular Impingement

    PubMed Central

    Mayer, Stephanie W.; Wagner, Naomi; Fields, Kara G.; Wentzel, Catherine; Burge, Alissa; Potter, Hollis G.; Lyman, Stephen; Kelly, Bryan T.

    2016-01-01

    Objectives: Cam-type femoroacetabular impingement (FAI) causes a shearing and delamination injury to the acetabular articular cartilage due to a mismatch between the size of the femoral head and the acetabulum. This mechanism is thought to lead to early osteoarthritis in this population. Cam decompression has been advocated to eliminate impingement, with the ultimate goal of halting the progression of articular cartilage delamination. Although outcomes following this procedure in the young adult population have been favorable at short and medium term follow up, it is not known whether the articular cartilage itself is protected from further injury by changing the biomechanics of the joint with decompression of the cam morphology. The purpose of this study is to compare the pre- and post-operative integrity of the acetabular articular cartilage using T2 mapping to determine if hip arthroscopy is protective of the articular cartilage at short- to medium term follow up. Methods: Males between 18 and 35 years of age who had pre-operative T2 mapping MRIs, underwent hip arthroscopy for cam or mixed-type FAI with an alpha angle greater than 50°, and had at least 2 year follow-up were identified. Post-operative MRIs were performed and T2 relaxation times in the transition zone and weight bearing articular cartilage in the anterosuperior acetabulum at deep and superficial chondral layers were recorded at nine points on three sagittal sequences on pre and post-operative MRIs. A paired t-test was used to compare T2 relaxation values between pre-operative and post-operative scans. Results: Eleven hips were evaluated. Mean age was 26.3 years (range 21 - 35). Mean follow up time to post-operative T2 mapping MRI was 2.6 years (range 2.4 - 2.7). The change in T2 relaxation time was not significantly different between pre- and post-operative MRI scans for any of the nine regions in the deep zone of the acetabular cartilage (p=0.065 - 0.969) or the superficial zone of the

  14. The Role of Tissue Engineering in Articular Cartilage Repair and Regeneration

    PubMed Central

    Zhang, Lijie; Hu, Jerry; Athanasiou, Kyriacos A.

    2011-01-01

    Articular cartilage repair and regeneration continue to be largely intractable due to the poor regenerative properties of this tissue. The field of articular cartilage tissue engineering, which aims to repair, regenerate, and/or improve injured or diseased articular cartilage functionality, has evoked intense interest and holds great potential for improving articular cartilage therapy. This review provides an overall description of the current state and progress in articular cartilage repair and regeneration. Traditional therapies and related problems are introduced. More importantly, a variety of promising cell sources, biocompatible tissue engineered scaffolds, scaffoldless techniques, growth factors, and mechanical stimuli used in current articular cartilage tissue engineering are reviewed. Finally, the technical and regulatory challenges of articular cartilage tissue engineering and possible future directions are discussed. PMID:20201770

  15. Treatment of articular cartilage lesions of the knee

    PubMed Central

    Falah, Mazen; Nierenberg, Gabreil; Soudry, Michael; Hayden, Morris

    2010-01-01

    Treatment of articular cartilage lesions in the knee remains a challenge for the practising orthopaedic surgeon. A wide range of options are currently practised, ranging from conservative measures through various types of operations and, recently, use of growth factors and emerging gene therapy techniques. The end result of these methods is usually a fibrous repair tissue (fibrocartilage), which lacks the biomechanical characteristics of hyaline cartilage that are necessary to withstand the compressive forces distributed across the knee. The fibrocartilage generally deteriorates over time, resulting in a return of the original symptoms and occasionally reported progression to osteoarthritis. Our purpose in this study was to review the aetiology, pathogenesis and treatment options for articular cartilage lesions of the knee. At present, autologous cell therapies, growth factor techniques and biomaterials offer more promising avenues of research to find clinical answers. PMID:20162416

  16. Study of the collagen structure in the superficial zone and physiological state of articular cartilage using a 3D confocal imaging technique

    PubMed Central

    Wu, Jian P; Kirk, Thomas B; Zheng, Ming H

    2008-01-01

    Introduction The collagen structure in the superficial zone of articular cartilage is critical to the tissue's durability. Early osteoarthritis is often characterized with fissures on the articular surface. This is closely related to the disruption of the collagen network. However, the traditional histology can not offer visualization of the collagen structure in articular cartilage because it uses conventional optical microscopy that does not have insufficient imaging resolution to resolve collagen from proteoglycans in hyaline articular cartilage. This study examines the 3D collagen network of articular cartilage scored from 0 to 2 in the scoring system of International Cartilage Repair Society, and aims to develop a 3D histology for assessing early osteoarthritis. Methods Articular cartilage was visually classified into five physiological groups: normal cartilage, aged cartilage, cartilage with artificial and natural surface disruption, and fibrillated. The 3D collagen matrix of the cartilage was acquired using a 3D imaging technique developed previously. Traditional histology was followed to grade the physiological status of the cartilage in the scoring system of International Cartilage Repair Society. Results Normal articular cartilage contains interwoven collagen bundles near the articular surface, approximately within the lamina splendens. However, its collagen fibres in the superficial zone orient predominantly in a direction spatially oblique to the articular surface. With age and disruption of the articular surface, the interwoven collagen bundles are gradually disappeared, and obliquely oriented collagen fibres change to align predominantly in a direction spatially perpendicular to the articular surface. Disruption of the articular surface is well related to the disappearance of the interwoven collagen bundles. Conclusion A 3D histology has been developed to supplement the traditional histology and study the subtle changes in the collagen network in the

  17. Intra-Articular Injections of Polyphenols Protect Articular Cartilage from Inflammation-Induced Degradation: Suggesting a Potential Role in Cartilage Therapeutics.

    PubMed

    Natarajan, Venkatachalam; Madhan, Balaraman; Tiku, Moti L

    2015-01-01

    Arthritic diseases, such as osteoarthritis and rheumatoid arthritis, inflict an enormous health care burden on society. Osteoarthritis, a degenerative joint disease with high prevalence among older people, and rheumatoid arthritis, an autoimmune inflammatory disease, both lead to irreversible structural and functional damage to articular cartilage. The aim of this study was to investigate the effect of polyphenols such as catechin, quercetin, epigallocatechin gallate, and tannic acid, on crosslinking type II collagen and the roles of these agents in managing in vivo articular cartilage degradation. The thermal, enzymatic, and physical stability of bovine articular cartilage explants following polyphenolic treatment were assessed for efficiency. Epigallocatechin gallate and tannic acid-treated explants showed >12 °C increase over native cartilage in thermal stability, thereby confirming cartilage crosslinking. Polyphenol-treated cartilage also showed a significant reduction in the percentage of collagen degradation and the release of glycosaminoglycans against collagenase digestion, indicating the increase physical integrity and resistance of polyphenol crosslinked cartilage to enzymatic digestion. To examine the in vivo cartilage protective effects, polyphenols were injected intra-articularly before (prophylactic) and after (therapeutic) the induction of collagen-induced arthritis in rats. The hind paw volume and histomorphological scoring was done for cartilage damage. The intra-articular injection of epigallocatechin gallate and tannic acid did not significantly influence the time of onset or the intensity of joint inflammation. However, histomorphological scoring of the articular cartilage showed a significant reduction in cartilage degradation in prophylactic- and therapeutic-groups, indicating that intra-articular injections of polyphenols bind to articular cartilage and making it resistant to degradation despite ongoing inflammation. These studies establish

  18. Intra-Articular Injections of Polyphenols Protect Articular Cartilage from Inflammation-Induced Degradation: Suggesting a Potential Role in Cartilage Therapeutics

    PubMed Central

    Natarajan, Venkatachalam; Madhan, Balaraman; Tiku, Moti L.

    2015-01-01

    Arthritic diseases, such as osteoarthritis and rheumatoid arthritis, inflict an enormous health care burden on society. Osteoarthritis, a degenerative joint disease with high prevalence among older people, and rheumatoid arthritis, an autoimmune inflammatory disease, both lead to irreversible structural and functional damage to articular cartilage. The aim of this study was to investigate the effect of polyphenols such as catechin, quercetin, epigallocatechin gallate, and tannic acid, on crosslinking type II collagen and the roles of these agents in managing in vivo articular cartilage degradation. The thermal, enzymatic, and physical stability of bovine articular cartilage explants following polyphenolic treatment were assessed for efficiency. Epigallocatechin gallate and tannic acid-treated explants showed >12 °C increase over native cartilage in thermal stability, thereby confirming cartilage crosslinking. Polyphenol-treated cartilage also showed a significant reduction in the percentage of collagen degradation and the release of glycosaminoglycans against collagenase digestion, indicating the increase physical integrity and resistance of polyphenol crosslinked cartilage to enzymatic digestion. To examine the in vivo cartilage protective effects, polyphenols were injected intra-articularly before (prophylactic) and after (therapeutic) the induction of collagen-induced arthritis in rats. The hind paw volume and histomorphological scoring was done for cartilage damage. The intra-articular injection of epigallocatechin gallate and tannic acid did not significantly influence the time of onset or the intensity of joint inflammation. However, histomorphological scoring of the articular cartilage showed a significant reduction in cartilage degradation in prophylactic- and therapeutic-groups, indicating that intra-articular injections of polyphenols bind to articular cartilage and making it resistant to degradation despite ongoing inflammation. These studies establish

  19. The determination of apoptosis rates on articular cartilages of ovariectomized rats with and without alendronate treatment.

    PubMed

    Acar, Nuray; Balkarli, Huseyin; Soyuncu, Yetkin; Ozbey, Ozlem; Celik-Ozenci, Ciler; Korkusuz, Petek; Ustunel, Ismail

    2016-06-01

    Osteoporosis (OP) is a major health problem characterized by compromised bone strength. Osteoarthritis (OA) is a joint disease that progresses slowly and is characterized by breakdown of the cartilage matrix. Alendronate (ALN), a nitrogen-containing bisphosphonate (BIS), inhibits bone loss and increases bone mineralization, and has been used clinically for the treatment of OP. It is still controversial whether BIS is effective in inhibiting the progression of OA. Chondrocyte apoptosis has been described in both human and experimentally induced OA models. In our study we aimed to detect whether ALN could protect articular cartilage from degeneration and reduce apoptosis rates in experimentally OA induced rats. For this rats were ovariectomized (ovex), nine weeks after operation rats were injected 30 µg/kg/week ALN subcutaneously for six weeks. After six weeks articular cartilages were obtained. We did Safranin O staining and Mankin and Pritzker scorings to evaluate degeneration and investigated the expressions of p53, cleaved caspase 3, Poly ADP-ribose (PAR), Poly ADP-ribose polymerase 1 (PARP 1), and applied TUNEL technique to determine apoptotis rates. We found a significant decrease in glycosaminoglycan (GAG) amount and increased apoptosis which indicates damage on articular cartilages of ovex rats. GAG amount was higher and apoptosis rate was lower on articular cartilages of ALN treated ovex rats compared to the ovex group. In contrary to studies showing that early ALN treatment has a protective effect, our study shows late ALN treatment has a chondroprotective effect on articular cartilage since we treated rats nine weeks after ovariectomy. PMID:26631351

  20. Hydrogels for the Repair of Articular Cartilage Defects

    PubMed Central

    Maher, Suzanne A.; Lowman, Anthony M.

    2011-01-01

    The repair of articular cartilage defects remains a significant challenge in orthopedic medicine. Hydrogels, three-dimensional polymer networks swollen in water, offer a unique opportunity to generate a functional cartilage substitute. Hydrogels can exhibit similar mechanical, swelling, and lubricating behavior to articular cartilage, and promote the chondrogenic phenotype by encapsulated cells. Hydrogels have been prepared from naturally derived and synthetic polymers, as cell-free implants and as tissue engineering scaffolds, and with controlled degradation profiles and release of stimulatory growth factors. Using hydrogels, cartilage tissue has been engineered in vitro that has similar mechanical properties to native cartilage. This review summarizes the advancements that have been made in determining the potential of hydrogels to replace damaged cartilage or support new tissue formation as a function of specific design parameters, such as the type of polymer, degradation profile, mechanical properties and loading regimen, source of cells, cell-seeding density, controlled release of growth factors, and strategies to cause integration with surrounding tissue. Some key challenges for clinical translation remain, including limited information on the mechanical properties of hydrogel implants or engineered tissue that are necessary to restore joint function, and the lack of emphasis on the ability of an implant to integrate in a stable way with the surrounding tissue. Future studies should address the factors that affect these issues, while using clinically relevant cell sources and rigorous models of repair. PMID:21510824

  1. Radiation synovectomy stimulates glycosaminoglycan synthesis by normal articular cartilage

    SciTech Connect

    Myers, S.L.; Slowman, S.D.; Brandt, K.D.

    1989-07-01

    Radiation synovectomy has been considered a therapeutic alternative to surgical synovectomy. Whether intraarticular irradiation affects the composition or biochemistry, and therefore the biomechanical properties, of normal articular cartilage has not been established. In the present study, yttrium 90 silicate was injected into one knee of nine normal adult dogs, and three other dogs received nonradioactive yttrium silicate. When the animals were killed 4 to 13 weeks after the injection, synovium from the irradiated knees showed areas of necrosis and fibrosis. Up to 29% less hyaluronate was synthesized in vitro by the synovial intima from irradiated knees than by the intima from the contralateral knees (mean difference 18%). Morphologic abnormalities were not observed in articular cartilage from either the irradiated or control knees, nor did the water content or concentrations of uronic acid or DNA in cartilage from the irradiated knees differ from that in cartilage from the contralateral knees. However, net /sup 35/SO/sub 4/-labeled glycosaminoglycan synthesis in organ cultures of cartilage from irradiated knees was increased (mean difference 21%, p = 0.03) in comparison with that in cultures of contralateral knee cartilage.

  2. Current Concepts of Articular Cartilage Restoration Techniques in the Knee

    PubMed Central

    Camp, Christopher L.; Stuart, Michael J.; Krych, Aaron J.

    2014-01-01

    Context: Articular cartilage injuries are common in patients presenting to surgeons with primary complaints of knee pain or mechanical symptoms. Treatment options include comprehensive nonoperative management, palliative surgery, joint preservation operations, and arthroplasty. Evidence Acquisition: A MEDLINE search on articular cartilage restoration techniques of the knee was conducted to identify outcome studies published from 1993 to 2013. Special emphasis was given to Level 1 and 2 published studies. Study Design: Clinical review. Level of Evidence: Level 3. Results: Current surgical options with documented outcomes in treating chondral injuries in the knee include the following: microfracture, osteochondral autograft transfer, osteochondral allograft transplant, and autologous chondrocyte transplantation. Generally, results are favorable regarding patient satisfaction and return to sport when proper treatment algorithms and surgical techniques are followed, with 52% to 96% of patients demonstrating good to excellent clinical outcomes and 66% to 91% returning to sport at preinjury levels. Conclusion: Clinical, functional, and radiographic outcomes may be improved in the majority of patients with articular cartilage restoration surgery; however, some patients may not fully return to their preinjury activity levels postoperatively. In active and athletic patient populations, biological techniques that restore the articular surface may be options that provide symptom relief and return patients to their prior levels of function. PMID:24790697

  3. Telomere erosion and senescence in human articular cartilage chondrocytes.

    PubMed

    Martin, J A; Buckwalter, J A

    2001-04-01

    Aging and the degeneration of articular cartilage in osteoarthritis are distinct processes, but a strong association exists between age and the incidence and prevalence of osteoarthritis. We hypothesized that this association is due to in vivo replicative senescence, which causes age-related declines in the ability of chondrocytes to maintain articular cartilage. For this hypothesis to be tested, senescence-associated markers were measured in human articular chondrocytes from donors ranging in age from 1 to 87 years. These measures included in situ staining for senescence-associated beta-galactosidase activity, (3)H-thymidine incorporation assays for mitotic activity, and Southern blots for telomere length determinations. We found that senescence-associated beta-galactosidase activity increased with age, whereas both mitotic activity and mean telomere length declined. These findings indicate that chondrocyte replicative senescence occurs in vivo and support the hypothesis that the association between osteoarthritis and aging is due in part to replicative senescence. The data also imply that transplantation procedures performed to restore damaged articular surfaces could be limited by the inability of older chondrocytes to form new cartilage after transplantation. PMID:11283188

  4. Surgical Treatment of Articular Cartilage Defects in the Knee: Are We Winning?

    PubMed Central

    Memon, A. R.; Quinlan, J. F.

    2012-01-01

    Articular cartilage (AC) injury is a common disorder. Numerous techniques have been employed to repair or regenerate the cartilage defects with varying degrees of success. Three commonly performed techniques include bone marrow stimulation, cartilage repair, and cartilage regeneration. This paper focuses on current level of evidence paying particular attention to cartilage regeneration techniques. PMID:22655202

  5. An in vitro model for the pathological degradation of articular cartilage in osteoarthritis.

    PubMed

    Grenier, Stephanie; Bhargava, Madhu M; Torzilli, Peter A

    2014-02-01

    The objective of this study was to develop an in vitro cartilage degradation model that emulates the damage seen in early-stage osteoarthritis. To this end, cartilage explants were collagenase-treated to induce enzymatic degradation of collagen fibers and proteoglycans at the articular surface. To assess changes in mechanical properties, intact and degraded cartilage explants were subjected to a series of confined compression creep tests. Changes in extracellular matrix structure and composition were determined using biochemical and histological approaches. Our results show that collagenase-induced degradation increased the amount of deformation experienced by the cartilage explants under compression. An increase in apparent permeability as well as a decrease in instantaneous and aggregate moduli was measured following collagenase treatment. Histological analysis of degraded explants revealed the presence of surface fibrillation, proteoglycan depletion in the superficial and intermediate zones and loss of the lamina splendens. Collagen cleavage was confirmed by the Col II-3/4Cshort antibody. Degraded specimens experienced a significant decrease in proteoglycan content but maintained total collagen content. Repetitive testing of degraded samples resulted in the gradual collapse of the articular surface and the compaction of the superficial zone. Taken together, our data demonstrates that enzymatic degradation with collagenase can be used to emulate changes seen in early-stage osteoarthritis. Further, our in vitro model provides information on cartilage mechanics and insights on how matrix changes can affect cartilage's functional properties. More importantly, our model can be applied to develop and test treatment options for tissue repair. PMID:24360770

  6. Cartilage damage involving extrusion of mineralisable matrix from the articular calcified cartilage and subchondral bone.

    PubMed

    Boyde, A; Riggs, C M; Bushby, A J; McDermott, B; Pinchbeck, G L; Clegg, P D

    2011-01-01

    Arthropathy of the distal articular surfaces of the third metacarpal (Mc3) and metatarsal (Mt3) bones in the Thoroughbred racehorse (Tb) is a natural model of repetitive overload arthrosis. We describe a novel pathology that affects the articular calcified cartilage (ACC) and subchondral bone (SCB) and which is associated with hyaline articular cartilage degeneration. Parasagittal slices cut from the palmar quadrant of the distal condyles of the left Mc3/Mt3 of 39 trained Tbs euthanized for welfare reasons were imaged by point projection microradiography, and backscattered electron (BSE) scanning electron microscopy (SEM), light microscopy, and confocal scanning light microscopy. Mechanical properties were studied by nanoindentation. Data on the horses' training and racing career were also collected. Highly mineralised projections were observed extending from cracks in the ACC mineralising front into the hyaline articular cartilage (HAC) up to two-thirds the thickness of the HAC, and were associated with focal HAC surface fibrillation directly overlying their site. Nanoindentation identified this extruded matrix to be stiffer than any other mineralised phase in the specimen by a factor of two. The presence of projections was associated with a higher cartilage Mankin histology score (P<0.02) and increased amounts of gross cartilage loss pathologically on the condyle (P<0.02). Presence of projections was not significantly associated with: total number of racing seasons, age of horse, amount of earnings, number of days in training, total distance galloped in career, or presence of wear lines. PMID:21623571

  7. Effects of surgically induced instability on rat knee articular cartilage.

    PubMed Central

    Williams, J M; Felten, D L; Peterson, R G; O'Connor, B L

    1982-01-01

    Degenerative lesions in the articular cartilage were present following transection of the anterior cruciate ligament in the rat. These lesions included surface disruptions, a reduction in matrix proteoglycans, and cellular changes and therefore were similar to lesions seen in dogs following transection of the anterior cruciate ligament as well as lesions seen in other mechanical derangement models. Lesions were more frequently encountered in animals that had been exercised on a treadmill. This suggests that the rat knee joint may be a useful small animal model in studying the effect of mechanical derangement on articular tissues. Images Figs. 1-2 Figs. 3-4 Figs. 5-6 PMID:7076535

  8. Fucose content of keratan sulphates from bovine articular cartilage.

    PubMed Central

    Tai, G H; Brown, G M; Morris, H G; Huckerby, T N; Nieduszynski, I A

    1991-01-01

    Alkaline-borohydride-reduced keratan sulphate chains were isolated from bovine articular cartilage (6-8-year-old animals). Nine keratan sulphate fractions of increasing molecular weight were prepared by gel-permeation chromatography on a calibrated column of TSK 30 XL. The samples were analysed for fucose and galactose contents (% by wt. of keratan sulphate) and fucose/galactose ratio. The fucose content increased with molecular size, but the galactose content remained constant. It was concluded that the alpha(1----3)-linked fucose [Thornton, Morris, Cockin, Huckerby, Nieduszynski, Carlstedt, Hardingham & Ratcliffe (1989) Biochem. J. 260, 277-282] was located within the poly-N-acetyl-lactosamine repeat sequence of articular-cartilage keratan sulphate. PMID:1991030

  9. Structural and metabolic changes in articular cartilage induced by iodoacetate.

    PubMed Central

    Dunham, J.; Hoedt-Schmidt, S.; Kalbhen, D. A.

    1992-01-01

    The chemically induced injury to articular cartilage, caused by two successive intra-articular injections of sodium iodoacetate, has been used in studies on the effects of anti-inflammatory and of potentially chondroprotective agents. It has been assumed that the injurious effects are caused by inhibition of the glycolytic pathway. In the present study this inhibition has been shown to be greater than expected from in vitro studies, and to influence equally other oxidative pathways. However, the response is clearly not a simple one in that some of the surface chondrocytes, and synovial lining cells in close proximity to the cartilage, show virtually no inhibition. Images Fig. 2 Fig. 3 Fig. 4 PMID:1390193

  10. 3D braid scaffolds for regeneration of articular cartilage.

    PubMed

    Ahn, Hyunchul; Kim, Kyoung Ju; Park, Sook Young; Huh, Jeong Eun; Kim, Hyun Jeong; Yu, Woong-Ryeol

    2014-06-01

    Regenerating articular cartilage in vivo from cultured chondrocytes requires that the cells be cultured and implanted within a biocompatible, biodegradable scaffold. Such scaffolds must be mechanically stable; otherwise chondrocytes would not be supported and patients would experience severe pain. Here we report a new 3D braid scaffold that matches the anisotropic (gradient) mechanical properties of natural articular cartilage and is permissive to cell cultivation. To design an optimal structure, the scaffold unit cell was mathematically modeled and imported into finite element analysis. Based on this analysis, a 3D braid structure with gradient axial yarn distribution was designed and manufactured using a custom-built braiding machine. The mechanical properties of the 3D braid scaffold were evaluated and compared with simulated results, demonstrating that a multi-scale approach consisting of unit cell modeling and continuum analysis facilitates design of scaffolds that meet the requirements for mechanical compatibility with tissues. PMID:24556323

  11. Finite element formulation of biphasic poroviscoelastic model for articular cartilage.

    PubMed

    Suh, J K; Bai, S

    1998-04-01

    The purpose of the present study was to develop a computationally efficient finite element model that could be useful for parametric analysis of the biphasic poroviscoelastic (BPVE) behavior of articular cartilage under various loading conditions. The articular cartilage was modeled as the BPVE mixture of a porous, linear viscoelastic, and incompressible solid and an inviscid and incompressible fluid. A finite element (FE) formulation of the BPVE model was developed using two different algorithms, the continuous and discrete spectrum relaxation functions for the viscoelasticity of the solid matrix. These algorithms were applied to the creep and stress relaxation responses to the confined compression of articular cartilage, and a comparison of their performances was made. It was found that the discrete spectrum algorithm significantly saved CPU time and memory, as compared to the continuous spectrum algorithm. The consistency analysis for the present FE formulation was performed in comparison with the IMSL, a commercially available numerical software package. It was found that the present FE formulation yielded consistent results in predicting model behavior, whereas the IMSL subroutine produced inconsistent results in the velocity field, and thereby in the strain calculation. PMID:10412380

  12. Repair and tissue engineering techniques for articular cartilage

    PubMed Central

    Makris, Eleftherios A.; Gomoll, Andreas H.; Malizos, Konstantinos N.; Hu, Jerry C.; Athanasiou, Kyriacos A.

    2015-01-01

    Chondral and osteochondral lesions due to injury or other pathology commonly result in the development of osteoarthritis, eventually leading to progressive total joint destruction. Although current progress suggests that biologic agents can delay the advancement of deterioration, such drugs are incapable of promoting tissue restoration. The limited ability of articular cartilage to regenerate renders joint arthroplasty an unavoidable surgical intervention. This Review describes current, widely used clinical repair techniques for resurfacing articular cartilage defects; short-term and long-term clinical outcomes of these techniques are discussed. Also reviewed is a developmental pipeline of regenerative biological products that over the next decade could revolutionize joint care by functionally healing articular cartilage. These products include cell-based and cell-free materials such as autologous and allogeneic cell-based approaches and multipotent and pluripotent stem-cell-based techniques. Central to these efforts is the prominent role that tissue engineering has in translating biological technology into clinical products; therefore, concomitant regulatory processes are also discussed. PMID:25247412

  13. The collagen fibril organization in human articular cartilage.

    PubMed Central

    Minns, R J; Steven, F S

    1977-01-01

    In this scanning electron microscopic study blocks of collagen fibrils were prepared from human articular cartilage, using two techinques which selectively removed either the proteoglycans alone, or both the proteoglycans and the collagen fibrils, of the non-calcified cartilage layer. Amino acid analysis of the fibrils confirmed the purity of the collagen after proteoglycan extraction. The cartilage was scanned in four different ways: (1) normal to the articular surface, (2) in superficial sections, (3) on surfaces of blocks which had been broken in planes parallel to artificial splits make by the insertion of a pin, and (4) on fracture surfaces which traversed the calcified cartilage and the subchondral bone. Five features of the organization of the collagen fibrils were specially noted: (1) Individual fibrils within the trabeculae joined to form small fibre bundles which became grouped into larger bundles at the calcified/uncalcified interface. (2) Fibrils in the deep and middle zones which, exhibiting the characteristic surface periodicity of collagen, were generally oriented towars the articular surface in large bundles approximately 55 micronm across. (3) In the superficial zone, fibrils ran parallel to the surface. (4) The surface fibrils had random orientation, even at the bases of empty lacunae vacated by chondrocytes during specimen preparation. (5) The collagen fibrils of the lacunar walls appeared to be thinner and more closely packed than thos between the lacunae. The fine collagen fibrils associated with the lacunar walls were frequently observed to pass through a large lacunar space, resulting in the formation of two or more compartments, each of which was presumably filled with a chondrocyte in the living cartilage. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 Fig. 14 PMID:870478

  14. Postnatal development of collagen structure in ovine articular cartilage

    PubMed Central

    2010-01-01

    Background Articular cartilage (AC) is the layer of tissue that covers the articulating ends of the bones in diarthrodial joints. Across species, adult AC shows an arcade-like structure with collagen predominantly perpendicular to the subchondral bone near the bone, and collagen predominantly parallel to the articular surface near the articular surface. Recent studies into collagen fibre orientation in stillborn and juvenile animals showed that this structure is absent at birth. Since the collagen structure is an important factor for AC mechanics, the absence of the adult Benninghoff structure has implications for perinatal AC mechanobiology. The current objective is to quantify the dynamics of collagen network development in a model animal from birth to maturity. We further aim to show the presence or absence of zonal differentiation at birth, and to assess differences in collagen network development between different anatomical sites of a single joint surface. We use quantitative polarised light microscopy to investigate properties of the collagen network and we use the sheep (Ovis aries) as our model animal. Results Predominant collagen orientation is parallel to the articular surface throughout the tissue depth for perinatal cartilage. This remodels to the Benninghoff structure before the sheep reach sexual maturity. Remodelling of predominant collagen orientation starts at a depth just below the future transitional zone. Tissue retardance shows a minimum near the articular surface at all ages, which indicates the presence of zonal differentiation at all ages. The absolute position of this minimum does change between birth and maturity. Between different anatomical sites, we find differences in the dynamics of collagen remodelling, but no differences in adult collagen structure. Conclusions The collagen network in articular cartilage remodels between birth and sexual maturity from a network with predominant orientation parallel to the articular surface to a

  15. Characterization of enzymatically induced degradation of articular cartilage using high frequency ultrasound

    NASA Astrophysics Data System (ADS)

    Töyräs, J.; Rieppo, J.; Nieminen, M. T.; Helminen, H. J.; Jurvelin, J. S.

    1999-11-01

    Ultrasound may provide a quantitative technique for the characterization of cartilage changes typical of early osteoarthrosis. In this study, specific changes in bovine articular cartilage were induced using collagenase and chondroitinase ABC, enzymes that selectively degrade collagen fibril network and digest proteoglycans, respectively. Changes in cartilage structure and properties were quantified using high frequency ultrasound, microscopic analyses and mechanical indentation tests. The ultrasound reflection coefficient of the physiological saline-cartilage interface (R1) decreased significantly (-96.4%, p<0.01) in the collagenase digested cartilage compared to controls. Also a significantly lower ultrasound velocity (-6.2%, p<0.01) was revealed after collagenase digestion. After chondroitinase ABC digestion, a new acoustic interface at the depth of the enzyme penetration front was detected. Cartilage thickness, as determined with ultrasound, showed a high, linear correlation (R = 0.943, n = 60, average difference 0.073 mm (4.0%)) with the thickness measured by the needle-probe method. Both enzymes induced a significant decrease in the Young's modulus of cartilage (p<0.01). Our results indicate that high frequency ultrasound provides a sensitive technique for the analysis of cartilage structure and properties. Possibly ultrasound may be utilized in vivo as a quantitative probe during arthroscopy.

  16. Analysis of friction between articular cartilage and polyvinyl alcohol hydrogel artificial cartilage.

    PubMed

    Li, Feng; Wang, Anmin; Wang, Chengtao

    2016-05-01

    Many biomaterials are being used to repair damaged articular cartilage. In particular, poly vinyl alcohol hydrogel has similar mechanical properties to natural cartilage under compressive and shearing loading. Here, three-factor and two-level friction experiments and long-term tests were conducted to better evaluate its tribological properties. The friction coefficient between articular cartilage and the poly vinyl alcohol hydrogel depended primarily on the three factors of load, speed, and lubrication. When the speed increased from 10 to 20 mm/s under a load of 10 N, the friction coefficient increased from 0.12 to 0.147. When the lubricant was changed from Ringer's solution to a hyaluronic acid solution, the friction coefficient decreased to 0.084 with loads as high as 22 N. The poly vinyl alcohol hydrogel was severely damaged and lost its top surface layers, which were transferred to the articular cartilage surface. Wear was observed in the surface morphologies, which indicated the occurrence of surface adhesion of bovine cartilage. Surface fatigue and adhesive wear was the dominant wear mechanism. PMID:26970769

  17. An In Vitro Model for the Pathological Degradation of Articular Cartilage in Osteoarthritis

    PubMed Central

    Grenier, Stephanie; Bhargava, Madhu M.; Torzilli, Peter A.

    2014-01-01

    The objective of this study was to develop an in vitro cartilage degradation model that emulates the damage seen in early-stage osteoarthritis. To this end, cartilage explants were collagenase-treated to induce enzymatic degradation of collagen fibers and proteoglycans at the articular surface. To assess changes in mechanical properties, intact and degraded cartilage explants were subjected to a series of confined compression creep tests. Changes in extracellular matrix structure and composition were determined using biochemical and histological approaches. Our results show that collagenase-induced degradation increased the amount of deformation experienced by the cartilage explants under compression. An increase in apparent permeability as well as a decrease in instantaneous and aggregate moduli were measured following collagenase treatment. Histological analysis of degraded explants revealed the presence of surface fibrillation, proteoglycan depletion in the superficial and intermediate zones and loss of the lamina splendens. Collagen cleavage was confirmed by the Col II–¾Cshort antibody. Degraded specimens experienced a significant decrease in proteoglycan content but maintained total collagen content. Repetitive testing of degraded samples resulted in the gradual collapse of the articular surface and the compaction of the superficial zone. Taken together, our data demonstrates that enzymatic degradation with collagenase can be used to emulate changes seen in early-stage osteoarthritis. Further, our in vitro model provides information on cartilage mechanics and insights on how matrix changes can affect cartilage’s functional properties. More importantly, our model can be applied to develop and test treatment options for tissue repair. PMID:24360770

  18. Treatment with recombinant lubricin attenuates osteoarthritis by positive feedback loop between articular cartilage and subchondral bone in ovariectomized rats.

    PubMed

    Cui, Zhuang; Xu, Changpeng; Li, Xue; Song, Jinqi; Yu, Bin

    2015-05-01

    Osteoarthritis (OA) is a most commonly multifactorial degenerative joint disease along with the aging population, particularly in postmenopausal women. During the onset of OA, articular cartilage and subchondral bone act in concert as a functional unit. This present study is to investigate the effects of early or late treatment with recombinant lubricin on the onset of osteoarthritis (OA) in ovariectomized (OVX) rats. We found that both early and late recombinant lubricin treatments attenuated the onset of OA by positive feedback loop between articular cartilage and subchondral bone, although late treatment contributed to a lesser effect compared with early treatment. Specifically, treatment with recombinant lubricin protected articular cartilage from degeneration, demonstrated by lower proteoglycan loss, lower OARSI scores, less calcification cartilage zone and reduced immunostaining for collagen X (Col X) and matrix metalloproteinase (MMP-13) but increased the expression of lubricin, in comparison with vehicle-treated OVX rat group. Further, chondroprotective effects of lubricin normalized bone remodeling in subchondral bone underneath. It's suggested that treatment with recombinant lubricin inhibited the elevation of TRAP and Osterix positive cells in OVX rats and led to the normalization of subchondral bone microarchitectures with the suppression of subsidence of bone volume ratio (BV/TV) and trabecular thickness (Tb.Th) and the increase of trabecular separation (Tb.Sp) in vehicle-treated OVX rats. What's more, the normalization of subchondral bone in turn attenuated the articular cartilage erosion by inhibiting vascular invasion from subchondral bone to calcified cartilage zone, exemplified by inhibiting the elevation of CD31 positive cells in calcified cartilage and angiography in subchondral bone. Together, these results shed light that both early and late recombinant lubricin treatments attenuate the onset of OA by balancing the interplay between articular

  19. Non-invasive and in vivo assessment of osteoarthritic articular cartilage: a review on MRI investigations.

    PubMed

    Hani, Ahmad Fadzil Mohd; Kumar, Dileep; Malik, Aamir Saeed; Ahmad, Raja Mohd Kamil Raja; Razak, Ruslan; Kiflie, Azman

    2015-01-01

    Early detection of knee osteoarthritis (OA) is of great interest to orthopaedic surgeons, rheumatologists, radiologists, and researchers because it would allow physicians to provide patients with treatments and advice to slow the onset or progression of the disease. Early detection can be achieved by identifying early changes in selected features of degenerative articular cartilage (AC) using non-invasive imaging modalities. Magnetic resonance imaging (MRI) is becoming the standard for assessment of OA. The aim of this paper was to review the influence of MRI on the selection, detection, and measurement of AC features associated with early OA. Our review of the literature indicates that the changes associated with early OA are in cartilage thickness, cartilage volume, cartilage water content, and proteoglycan content that can be accurately, consistently, and non-invasively measured using MRI. Choosing an MR pulse sequence that provides the capability to assess cartilage physiology and morphology in a single acquisition and advanced multi-nuclei MRI is desirable. The results of the review indicate that using an ultra-high magnetic strength, MR imager does not affect early OA detection. In conclusion, MRI is currently the most suitable modality for early detection of knee OA, and future research should focus on the quantitative evaluation of early OA features using advances in MR hardware, software, and data processing with sophisticated image/pattern recognition techniques. PMID:24879325

  20. Articular cartilage of the knee 3 years after ACL reconstruction

    PubMed Central

    Bae, Ji-Hoon; Hosseini, Ali; Wang, Yang; Torriani, Martin; Gill, Thomas J; Grodzinsky, Alan J

    2015-01-01

    Background and purpose T1ρ or T2 relaxation imaging has been increasingly used to evaluate the cartilage of the knee. We investigated the cartilage of ACL-reconstructed knees 3 years after surgery using T2 relaxation times. Patients and methods 10 patients with a clinically successful unilateral ACL reconstruction were examined 3 years after surgery. Multiple-TE fast-spin echo sagittal images of both knees were acquired using a 3T MRI scanner for T2 mapping of the tibiofemoral cartilage. T2 values of the superficial and deep zones of the tibiofemoral cartilage were analyzed in sub-compartmental areas and compared between the ACL-reconstructed and uninjured contralateral knees. Results Higher T2 values were observed in 1 or more sub-compartmental areas of each ACL-reconstructed knee compared to the uninjured contralateral side. Most of the T2 increases were observed at the superficial zones of the cartilage, especially at the medial compartment. At the medial compartment of the ACL-reconstructed knee, the T2 values of the femoral and tibial cartilage were increased by 3–81% compared to the uninjured contralateral side, at the superficial zones of the weight-bearing areas. T2 values in the superficial zone of the central medial femoral condyle differed between the 2 groups (p = 0.002). Interpretation The articular cartilage of ACL-reconstructed knees, although clinically satisfactory, had higher T2 values in the superficial zone of the central medial femoral condyle than in the uninjured contralateral side 3 years after surgery. Further studies are warranted to determine whether these patients would undergo cartilage degeneration over time. PMID:25854533

  1. Importance of reference gene selection for articular cartilage mechanobiology studies

    PubMed Central

    Al-Sabah, A.; Stadnik, P.; Gilbert, S.J.; Duance, V.C.; Blain, E.J.

    2016-01-01

    Summary Objective Identification of genes differentially expressed in mechano-biological pathways in articular cartilage provides insight into the molecular mechanisms behind initiation and/or progression of osteoarthritis (OA). Quantitative PCR (qPCR) is commonly used to measure gene expression, and is reliant on the use of reference genes for normalisation. Appropriate validation of reference gene stability is imperative for accurate data analysis and interpretation. This study determined in vitro reference gene stability in articular cartilage explants and primary chondrocytes subjected to different compressive loads and tensile strain, respectively. Design The expression of eight commonly used reference genes (18s, ACTB, GAPDH, HPRT1, PPIA, RPL4, SDHA and YWHAZ) was determined by qPCR and data compared using four software packages (comparative delta-Ct method, geNorm, NormFinder and BestKeeper). Calculation of geometric means of the ranked weightings was carried out using RefFinder. Results Appropriate reference gene(s) for normalisation of mechanically-regulated transcript levels in articular cartilage tissue or isolated chondrocytes were dependent on experimental set-up. SDHA, YWHAZ and RPL4 were the most stable genes whilst glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and to a lesser extent Hypoxanthine-guanine phosphoribosyltransferase (HPRT), showed variable expression in response to load, demonstrating their unsuitability in such in vitro studies. The effect of using unstable reference genes to normalise the expression of aggrecan (ACAN) and matrix metalloproteinase 3 (MMP3) resulted in inaccurate quantification of these mechano-sensitive genes and erroneous interpretation/conclusions. Conclusion This study demonstrates that commonly used ‘reference genes’ may be unsuitable for in vitro cartilage chondrocyte mechanobiology studies, reinforcing the principle that careful validation of reference genes is essential prior to each experiment to

  2. Ultrasound evaluation of site-specific effect of simulated microgravity on articular cartilage.

    PubMed

    Wang, Qing; Zheng, Yong-Ping; Wang, Xiao-Yun; Huang, Yan-Ping; Liu, Mu-Qing; Wang, Shu-Zhe; Zhang, Zong-Kang; Guo, Xia

    2010-07-01

    Space flight induces acute changes in normal physiology in response to the microgravity environment. Articular cartilage is subjected to high loads under a ground reaction force on Earth. The objectives of this study were to investigate the site dependence of morphological and ultrasonic parameters of articular cartilage and to examine the site-specific responses of articular cartilage to simulated microgravity using ultrasound biomicroscopy (UBM). Six rats underwent tail suspension (simulated microgravity) for four weeks and six other rats were kept under normal Earth gravity as controls. Cartilage thickness, ultrasound roughness index (URI), integrated reflection coefficient (IRC) and integrated backscatter coefficient (IBC) of cartilage tissues, as well as histological degeneration were measured at the femoral head (FH), medial femoral condyle (MFC), lateral femoral condyle (LFC), patello-femoral groove (PFG) and patella (PAT). The results showed site dependence not significant in all UBM parameters except cartilage thickness (p < 0.01) in the control specimens. Only minor changes in articular cartilage were induced by 4-week tail suspension, although there were significant decreases in cartilage thickness at the MFC and PAT (p < 0.05) and a significant increase in URI at the PAT (p < 0.01). This study suggested that the 4-week simulated microgravity had only mild effects on femoral articular cartilage in the rat model. This information is useful for human spaceflight and clinical medicine in improving understanding of the effect of microgravity on articular cartilage. However, the effects of longer duration microgravity experience on articular cartilage need further investigation. PMID:20620696

  3. Zn deposition at the bone cartilage interface in equine articular cartilage

    NASA Astrophysics Data System (ADS)

    Bradley, D. A.; Moger, C. J.; Winlove, C. P.

    2007-09-01

    In articular cartilage metalloproteinases, a family of enzymes whose function relies on the presence of divalent cations such as Zn and Ca plays a central role in the normal processes of growth and remodelling and in the degenerative and inflammatory processes of arthritis. Another important enzyme, alkaline phosphatase, involved in cartilage mineralisation also relies on metallic cofactors. The local concentration of divalent cations is therefore of considerable interest in cartilage pathophysiology and several authors have used synchrotron X-ray fluorescence (XRF) to map metal ion distributions in bone and cartilage. We report use of a bench-top XRF analytical microscope, providing spatial resolution of 10 μm and applicable to histological sections, facilitating correlation of the distribution with structural features. The study seeks to establish the elemental distribution in normal tissue as a precursor to investigation of changes in disease. For six samples prepared from equine metacarpophalangeal joint, we observed increased concentration of Zn and Sr ions around the tidemark between normal and mineralised cartilage. This is believed to be an active site of remodelling but its composition has hitherto lacked detailed characterization. We also report preliminary results on two of the samples using Proton-Induced X-ray Emission (PIXE). This confirms our previous observations using synchrotron-based XRF of enhanced deposition of Sr and Zn at the surface of the subchondral bone and in articular cartilage.

  4. Regeneration of Articular Cartilage Surface: Morphogens, Cells, and Extracellular Matrix Scaffolds.

    PubMed

    Sakata, Ryosuke; Iwakura, Takashi; Reddi, A Hari

    2015-10-01

    The articular cartilage is a well-organized tissue for smooth and friction-free joint movement for locomotion in animals and humans. Adult articular cartilage has a very low self-regeneration capacity due to its avascular nature. The regeneration of articular cartilage surface is critical to prevent the progression to osteoarthritis (OA). Although various joint resurfacing procedures in experimental articular cartilage defects have been developed, no standardized clinical protocol has yet been established. The three critical ingredients for tissue regeneration are morphogens and growth factors, cells, and scaffolds. The concepts based on the regeneration triad have been extensively investigated in animal models. However, these studies in animal models have demonstrated variable results and outcomes. An optimal animal model must precisely mimic and model the sequence of events in articular cartilage regeneration in human. In this article, the progress and remaining challenges in articular cartilage regeneration in animal models are reviewed. The role of individual morphogens and growth factors in cartilage regeneration has been investigated. In normal articular cartilage homeostasis, morphogens and growth factors function sequentially in tissue regeneration. Mesenchymal stem cell-based repair of articular cartilage defects, performed with or without various growth factors and scaffolds, has been widely attempted in animal models. Stem cells, including embryonic and adult stem cells and induced pluripotent stem cells, have also been reported as attractive cell sources for articular cartilage surface regeneration. Several studies with regard to scaffolds have been advanced, including recent investigations based on nanomaterials, functional mechanocompatible scaffolds, multilayered scaffolds, and extracellular matrix scaffolds for articular cartilage surface regeneration. Continuous refinement of animal models in chondral and osteochondral defects provide opportunities

  5. Effect of exercise on the proteoglycan metabolism of articular cartilage in growing foals.

    PubMed

    van den Hoogen, B M; van den Lest, C H; van Weeren, P R; van Golde, L M; Barneveld, A

    1999-11-01

    In this study, the effect of different exercise regimens on proteoglycan metabolism of articular cartilage was examined in 43 newborn foals randomly divided into 3 groups: a) box-rest, b) box-rest with training and c) free pasture exercise. They were subjected to these exercise regimens from ages 1 week to 5 months and at 5 months, 24 foals (8 from each group) were sacrificed to assess short-term exercise effects. The remaining 19 foals were subjected to the same regimen of light exercise for an additional 6 months before being sacrificed to evaluate possible long-term effects. Articular cartilage explants were cultured and proteoglycan synthesis, both ex vivo and after 4 days of serum stimulation, release of endogenous and newly synthesised proteoglycans, and DNA- and GAG contents were measured to determine the metabolic state of the cartilage. Cartilage metabolic parameters in the box-rest group at 5 months indicated a retardation in development of the cartilage but, after an additional 6 months, this retardation had almost completely disappeared. The training regimen induced an increase in proteoglycan synthesis at 5 months in cartilage that was, however, accompanied by an increase in proteoglycan release. In the training group at the long-term, the ability of cartilage to increase proteoglycan synthesis when stimulated was severely reduced. We consider this extra proteoglycan synthesis capacity of great importance to repair small injuries and hence as essential to prevent an early onset of degenerative disorders such as osteoarthritis. Therefore, although extrapolation of in vitro data to the in vivo situation always should be done with the utmost care, it is concluded that pasture exercise is best for the development of healthy cartilage resistant to injury and other exercise protocols may carry harmful long-term effects. PMID:10999662

  6. Stem cells for tissue engineering of articular cartilage.

    PubMed

    Gao, J; Yao, J Q; Caplan, A I

    2007-07-01

    Articular cartilage injuries are one of the most common disorders in the musculo-skeletal system. Injured cartilage tissue cannot spontaneously heal and, if not treated, can lead to osteoarthritis of the affected joints. Although a variety of procedures are being employed to repair cartilage damage, methods that result in consistent durable repair tissue are not yet available. Tissue engineering is a recently developed science that merges the fields of cell biology, engineering, material science, and surgery to regenerate new functional tissue. Three critical components in tissue engineering of cartilage are as follows: first, sufficient cell numbers within the defect, such as chondrocytes or multipotent stem cells capable of differentiating into chondrocytes; second, access to growth and differentiation factors that modulate these cells to differentiate through the chondrogenic lineage; third, a cell carrier or matrix that fills the defect, delivers the appropriate cells, and supports cell proliferation and differentiation. Stem cells that exist in the embyro or in adult somatic tissues are able to renew themselves through cell division without changing their phenotype and are able to differentiate into multiple lineages including the chondrogenic lineage under certain physiological or experimental conditions. Here the application of stem cells as a cell source for cartilage tissue engineering is reviewed. PMID:17822146

  7. Evaluation of Se-75 BISTAES as a potential articular cartilage imaging agent

    SciTech Connect

    Yu, S.W.K.

    1987-01-01

    The potential of Se-75 bis (..beta..-N,N,N-trimethylamino)-ethyl) selenide diiodide (Se-75 BISTAES) as an articular cartilage imaging agent for the early diagnosis of osteoarthritis was evaluated. The compound was synthesized and the identity was established. The radiochemical purity and stability were determined initially and over a two-month period of storage at three temperatures. The biodistribution of Se-75 BISTAES in rabbits and guinea pigs was studied. A high concentration of radioactivity was found in the knee and shoulder cartilage. The radioactivity in the cartilage was the highest at 15 minutes to one hour post-injection. In rabbits, the highest ratio of radioactivity in the cartilage to the surrounding tissues was about 30. A minimal ratio of 10 is required for nuclear medicine imaging. Nuclear medicine imaging conducted on rabbits demonstrated increased radioactivity in the articular cartilage in the knee and shoulder. The impression from the nuclear medicine images and the findings of the biodistribution study indicated that the route of excretion of Se-75 BISTAES was the urine. The in vitro binding between Se-75 BISTAES and chondroitin sulfate was determined by an equilibrium dialysis technique.

  8. MRI rotating frame relaxation measurements for articular cartilage assessment

    PubMed Central

    Ellermann, Jutta; Ling, Wen; Nissi, Mikko J.; Arendt, Elizabeth; Carlson, Cathy S.; Garwood, Michael; Michaeli, Shalom; Mangia, Silvia

    2015-01-01

    In the present work we introduced two MRI rotating frame relaxation methods, namely adiabatic T1ρ and Relaxation Along a Fictitious Field (RAFF), along with an inversion-prepared Magnetization Transfer (MT) protocol for assessment of articular cartilage. Given the inherent sensitivity of rotating frame relaxation methods to slow molecular motions that are relevant in cartilage, we hypothesized that adiabatic T1ρ and RAFF would have higher sensitivity to articular cartilage degradation as compared to laboratory frame T2 and MT. To test this hypothesis, a proteoglycan depletion model was used. Relaxation time measurements were performed at 0 and 48 hours in ten bovine patellar specimens, 5 of which were treated with trypsin and 5 untreated controls were stored under identical conditions in isotonic saline for 48 hours. Relaxation times measured at 48 hours were longer than those measured at 0 hours in both groups. The changes in T2 and MT relaxation times after 48 hours were approximately 3 times larger in the trypsin treated specimens as compared to the untreated group, whereas increases of adiabatic T1ρ and RAFF were 4 to 5 fold larger. Overall, these findings demonstrate a higher sensitivity of adiabatic T1ρ and RAFF to the trypsin-induced changes in bovine patellar cartilage as compared to the commonly used T2 and MT. Since adiabatic T1ρ and RAFF are advantageous for human applications as compared to standard continuous-wave T1ρ methods, adiabatic T1ρ and RAFF are promising tools for assessing cartilage degradation in clinical settings. PMID:23993794

  9. T2* mapping for articular cartilage assessment: principles, current applications, and future prospects.

    PubMed

    Hesper, Tobias; Hosalkar, Harish S; Bittersohl, Daniela; Welsch, Götz H; Krauspe, Rüdiger; Zilkens, Christoph; Bittersohl, Bernd

    2014-10-01

    With advances in joint preservation surgery that are intended to alter the course of osteoarthritis by early intervention, accurate and reliable assessment of the cartilage status is critical. Biochemically sensitive MRI techniques can add robust biomarkers for disease onset and progression, and therefore, could be meaningful assessment tools for the diagnosis and follow-up of cartilage abnormalities. T2* mapping could be a good alternative because it would combine the benefits of biochemical cartilage evaluation with remarkable features including short imaging time and the ability of high-resolution three-dimensional cartilage evaluation-without the need for contrast media administration or special hardware. Several in vitro and in vivo studies, which have elaborated on the potential of cartilage T2* assessment in various cartilage disease patterns and grades of degeneration, have been reported. However, much remains to be understood and certain unresolved questions have become apparent with these studies that are crucial to the further application of this technique. This review summarizes the principles of the technique and current applications of T2* mapping for articular cartilage assessment. Limitations of recent studies are discussed and the potential implications for patient care are presented. PMID:24643762

  10. Biomaterial scaffolds in cartilage-subchondral bone defects influencing the repair of autologous articular cartilage transplants.

    PubMed

    Fan, Wei; Wu, Chengtie; Miao, Xigeng; Liu, Gang; Saifzadeh, Siamak; Sugiyama, Sadahiro; Afara, Isaac; Crawford, Ross; Xiao, Yin

    2013-05-01

    The repair of articular cartilage typically involves the repair of cartilage-subchondral bone tissue defects. Although various bioactive materials have been used to repair bone defects, how these bioactive materials in subchondral bone defects influence the repair of autologous cartilage transplant remains unclear. The aim of this study was to investigate the effects of different subchondral biomaterial scaffolds on the repair of autologous cartilage transplant in a sheep model. Cylindrical cartilage-subchondral bone defects were created in the right femoral knee joint of each sheep. The subchondral bone defects were implanted with hydroxyapatite-β-tricalcium phosphate (HA-TCP), poly lactic-glycolic acid (PLGA)-HA-TCP dual-layered composite scaffolds (PLGA/HA-TCP scaffolds), or autologous bone chips. The autologous cartilage layer was placed on top of the subchondral materials. After 3 months, the effect of different subchondral scaffolds on the repair of autologous cartilage transplant was systematically studied by investigating the mechanical strength, structural integration, and histological responses. The results showed that the transplanted cartilage layer supported by HA-TCP scaffolds had better structural integration and higher mechanical strength than that supported by PLGA/HA-TCP scaffolds. Furthermore, HA-TCP-supported cartilage showed higher expression of acid mucosubstances and glycol-amino-glycan contents than that supported by PLGA/HA-TCP scaffolds. Our results suggested that the physicochemical properties, including the inherent mechanical strength and material chemistry of the scaffolds, play important roles in influencing the repair of autologous cartilage transplants. The study may provide useful information for the design and selection of proper subchondral biomaterials to support the repair of both subchondral bone and cartilage defects. PMID:22684516

  11. A reappraisal of the structure of normal canine articular cartilage.

    PubMed Central

    Dunham, J; Shackleton, D R; Billingham, M E; Bitensky, L; Chayen, J; Muir, I H

    1988-01-01

    It has been shown that some of the controversy over the structure of articular cartilage may be due to slight differences in the orientation of the sample that has been studied. As our decisive criterion we have used the simple physical fact that elongate proteins, such as collagen micelles, that can exhibit form-birefringence, had to show virtually straight extinction when viewed under crossed polars. The use of a variably adjustable microtome chuck facilitated small adjustments in the orientation of the cartilage to meet this criterion. Under these conditions, the collagen of the matrix has been shown to be aligned mainly perpendicularly to the surface which was bounded by a thin lamina in which the collagen showed birefringence at 90 degrees to that of the matrix. The conventionally described zonation of articular cartilage has been shown to be inadequate for that of the dog tibial plateau. The conventional Zone 2 has been shown to consist of two zones, Zones 2a and 2b, with different cell sizes, cell concentrations, and concentration of matrix components. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:3198487

  12. [Joint morphogenesis and development of permanent articular cartilage].

    PubMed

    Ohta, Yoichi; Iwamoto, Masahiro

    2011-06-01

    During limb skeletogenesis progenitor mesenchymal cells aggregate at specific times and sites to form continuous precartilaginous condensations. With time the condensations undergo chondrogenesis and give rise to cartilaginous anlagen that exhibit incipient synovial joints at each end. A multitude of factors regulates subdivision into discrete skeletal elements and the formation, organization, morphogenesis and structure of the joints. This review summarizes recent advance of joint morphogenesis and actions of key players of joint and articular cartilage formation. In addition, we would like to discuss possible direction to translate basic research findings towards treatment of joint diseases. PMID:21628794

  13. Aberrant Calreticulin Expression in Articular Cartilage of Dio2 Deficient Mice

    PubMed Central

    Bomer, Nils; Cornelis, Frederique M. F.; Ramos, Yolande F. M.; den Hollander, Wouter; Lakenberg, Nico; van der Breggen, Ruud; Storms, Lies; Slagboom, P. Eline; Lories, Rik J. U.; Meulenbelt, Ingrid

    2016-01-01

    Objective To identify intrinsic differences in cartilage gene expression profiles between wild-type- and Dio2-/--mice, as a mechanism to investigate factors that contribute to prolonged healthy tissue homeostasis. Methods Previously generated microarray-data (Illumina MouseWG-6 v2) of knee cartilage of wild-type and Dio2 -/- -mice were re-analyzed to identify differential expressed genes independent of mechanical loading conditions by forced treadmill-running. RT-qPCR and western blot analyses of overexpression and knockdown of Calr in mouse chondro-progenitor cells (ATDC5) were applied to assess the direct effect of differential Calr expression on cartilage deposition. Results Differential expression analyses of articular cartilage of Dio2-/- (N = 9) and wild-type-mice (N = 11) while applying a cutoff threshold (P < 0.05 (FDR) and FC > |1,5|) resulted in 1 probe located in Calreticulin (Calr) that was found significantly downregulated in Dio2-/- mice (FC = -1.731; P = 0.044). Furthermore, overexpression of Calr during early chondrogenesis in ATDC5 cells leads to decreased proteoglycan deposition and corresponding lower Aggrecan expression, whereas knocking down Calr expression does not lead to histological differences of matrix composition. Conclusion We here demonstrate that the beneficial homeostatic state of articular cartilage in Dio2-/- mice is accompanied with significant lower expression of Calr. Functional analyses further showed that upregulation of Calr expression could act as an initiator of cartilage destruction. The consistent association between Calr and Dio2 expression suggests that enhanced expression of these genes facilitate detrimental effects on cartilage integrity. PMID:27163789

  14. EFFECTS OF ENZYMATIC DEGRADATION ON THE FRICTIONAL RESPONSE OF ARTICULAR CARTILAGE IN STRESS RELAXATION

    PubMed Central

    Basalo, Ines M.; Raj, David; Krishnan, Ramaswamy; Chen, Faye H.; Hung, Clark T.; Ateshian, Gerard A.

    2010-01-01

    SUMMARY It was recently shown experimentally that the friction coefficient of articular cartilage correlates with the interstitial fluid pressurization, supporting the hypothesis that interstitial water pressurization plays a fundamental role in the frictional response by supporting most of the load during the early time response. A recent study showed that enzymatic treatment with chondroitinase ABC causes a decrease in the maximum fluid load support of bovine articular cartilage in unconfined compression. The hypothesis of this study is that treatment with chondroitinase ABC will increase the friction coefficient of articular cartilage in stress relaxation. Articular cartilage samples (n=34) harvested from the femoral condyles of five bovine knee joints (1–3 months-old) were tested in unconfined compression with simultaneous continuous sliding (±1.5 mm at 1 mm/s) under stress relaxation. Results showed a significantly higher minimum friction coefficient in specimens treated with 0.1 u/ml of chondroitinase ABC for 24 hours (μmin = 0.082 ± 0.024) compared to control specimens (μmin = 0.047 ± 0.014). Treated samples also exhibited higher equilibrium friction coefficient (μeq = 0.232 ± 0.049) than control samples (μeq = 0.184 ± 0.036), which suggest that the frictional response is greatly influenced by the degree of tissue degradation. The fluid load support was predicted from theory, and the maximum value (as a percentage of the total applied load) was lower in treated specimens (77 ± 12%) than in control specimens (85 ± 6%). Based on earlier findings, the increase in the ratio μmin/μeq may be attributed to the decrease in fluid load support. PMID:15863119

  15. Black Colouration of the Knee Articular Cartilage after Spontaneously Recurrent Haemarthrosis

    PubMed Central

    Ishimaru, Daichi; Ogawa, Hiroyasu; Akiyama, Haruhiko

    2016-01-01

    Mild discolouration of the articular cartilage is known to gradually occur during aging. However, pathological tissue pigmentation is occasionally induced under several specific conditions. In the present case, we performed total knee replacement in a patient with recurrent haemarthrosis. However, during the operation, we observed severe black colouration of the knee articular cartilage, due to the deposition of hemosiderin and lipofuscin. To our knowledge, this is the first report of severe cartilage pigmentation, due to hemosiderin and lipofuscin deposition in articular cartilage. PMID:27293933

  16. Articular cartilage echography as a criterion of the evolution of osteoarthritis of the knee.

    PubMed

    Martino, F; Ettorre, G C; Patella, V; Macarini, L; Moretti, B; Pesce, V; Resta, L

    1993-01-01

    We propose a modification of the Aisen's technique by which precise reproducible measurements of articular cartilage thickness of the knee is possible. A group of 23 patients with severe osteoarthritis was studied by ultra-sound (US) before knee prosthesis surgery. Evaluation with US was performed by a real-time scanner with a 7.5 MHz linear probe with upper-patellar transverse scans tangent to the upper patellar pole at 90 degrees knee flexion. The cartilage thickness was measured within the weight-bearing area. After surgery, on the corresponding gross pathological specimen, US re-evaluation and histological measurements were made. Results of pre- and post-operative ultrasonography (US) data were compared with histological data and a good correlation between these measurements was found (p(t) > 10%). Preoperative measurements ranged from 2.4 to 0.3 mm. In order to obtain normal reference values of the articular cartilage within the weight-bearing area of the femoral trochlea for comparison, a group of 10 control subjects was also studied with US as above. The US data were then compared with computed tomography (arthro-CT) evaluations. No significant differences in mean values were found between the two imaging techniques (2.2 mm versus 2.3 mm for the lateral condyle and 2.3 versus 2.3 for the medial condyle, respectively). We conclude that ultra-sound measurement of articular cartilage thickness of femoral condyles is a sensitive and reproducible technique which permits early diagnosis and management of knee arthropathy and also quantification of cartilage damage. PMID:7995680

  17. Probing articular cartilage damage and disease by quantitative magnetic resonance imaging

    PubMed Central

    Chan, Deva D.; Neu, Corey P.

    2013-01-01

    Osteoarthritis (OA) is a debilitating disease that reflects a complex interplay of biochemical, biomechanical, metabolic and genetic factors, which are often triggered by injury, and mediated by inflammation, catabolic cytokines and enzymes. An unmet clinical need is the lack of reliable methods that are able to probe the pathogenesis of early OA when disease-rectifying therapies may be most effective. Non-invasive quantitative magnetic resonance imaging (qMRI) techniques have shown potential for characterizing the structural, biochemical and mechanical changes that occur with cartilage degeneration. In this paper, we review the background in articular cartilage and OA as it pertains to conventional MRI and qMRI techniques. We then discuss how conventional MRI and qMRI techniques are used in clinical and research environments to evaluate biochemical and mechanical changes associated with degeneration. Some qMRI techniques allow for the use of relaxometry values as indirect biomarkers for cartilage components. Direct characterization of mechanical behaviour of cartilage is possible via other specialized qMRI techniques. The combination of these qMRI techniques has the potential to fully characterize the biochemical and biomechanical states that represent the initial changes associated with cartilage degeneration. Additionally, knowledge of in vivo cartilage biochemistry and mechanical behaviour in healthy subjects and across a spectrum of osteoarthritic patients could lead to improvements in the detection, management and treatment of OA. PMID:23135247

  18. A nonlinear biphasic viscohyperelastic model for articular cartilage.

    PubMed

    García, José Jaime; Cortés, Daniel Humberto

    2006-01-01

    Experiments on articular cartilage have shown nonlinear stress-strain curves under finite deformations as well as intrinsic viscous effects of the solid phase. The aim of this study was to propose a nonlinear biphasic viscohyperelastic model that combines the intrinsic viscous effects of the proteoglycan matrix with a nonlinear hyperelastic constitutive equation. The proposed equation satisfies objectivity and reduces for uniaxial loading to a solid type viscous model in which the actions of the springs are represented by the hyperelastic function proposed by Holmes and Mow [1990. J. Biomechanics 23, 1145-1156.]. Results of the model, that were efficiently implemented in an updated Lagrangian algorithm, were compared with experimental infinitesimal data reported by DiSilverstro and Suh [2001. J. Biomechanics 34, 519-525.] and showed acceptable fitting for the axial force (R(2)=0.991) and lateral displacement (R(2)=0.914) curves in unconfined compression as well as a good fitting of the axial indentation force curve (R(2)=0.982). In addition, the model showed an excellent fitting of finite-deformation confined compression stress relaxation data reported by Ateshian et al. [1997. J. Biomechanics 30, 1157-1164.] and Huang et al. [2005. J. Biomechanics 38, 799-809.] (R(2)=0.993 and R(2)=0.995, respectively). The constitutive equation may be used to represent the mechanical behavior of the proteoglycan matrix in a fiber reinforced model of articular cartilage. PMID:16316659

  19. 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.

  20. Modeling IL-1 induced degradation of articular cartilage.

    PubMed

    Kar, Saptarshi; Smith, David W; Gardiner, Bruce S; Li, Yang; Wang, Yang; Grodzinsky, Alan J

    2016-03-15

    In this study, we develop a computational model to simulate the in vitro biochemical degradation of articular cartilage explants sourced from the femoropatellar grooves of bovine calves. Cartilage explants were incubated in culture medium with and without the inflammatory cytokine IL-1α. The spatio-temporal evolution of the cartilage explant's extracellular matrix components is modelled. Key variables in the model include chondrocytes, aggrecan, collagen, aggrecanase, collagenase and IL-1α. The model is first calibrated for aggrecan homeostasis of cartilage in vivo, then for data on (explant) controls, and finally for data on the IL-1α driven proteolysis of aggrecan and collagen over a 4-week period. The model was found to fit the experimental data best when: (i) chondrocytes continue to synthesize aggrecan during the cytokine challenge, (ii) a one to two day delay is introduced between the addition of IL-1α to the culture medium and subsequent aggrecanolysis, (iii) collagen degradation does not commence until the total concentration of aggrecan (i.e. both intact and degraded aggrecan) at any specific location within the explant becomes ≤ 1.5 mg/ml and (iv) degraded aggrecan formed due to the IL-1α induced proteolysis of intact aggrecan protects the collagen network while collagen degrades in a two-step process which, together, significantly modulate the collagen network degradation. Under simulated in vivo conditions, the model predicts increased aggrecan turnover rates in the presence of synovial IL-1α, consistent with experimental observations. Such models may help to infer the course of events in vivo following traumatic joint injury, and may also prove useful in quantitatively evaluating the efficiency of various therapeutic molecules that could be employed to avoid or modify the course of cartilage disease states. PMID:26874194

  1. In Vivo Evaluation of a Novel Oriented Scaffold-BMSC Construct for Enhancing Full-Thickness Articular Cartilage Repair in a Rabbit Model

    PubMed Central

    Pan, Weimin; Liu, Jian; Sun, Wei

    2015-01-01

    Tissue engineering (TE) has been proven usefulness in cartilage defect repair. For effective cartilage repair, the structural orientation of the cartilage scaffold should mimic that of native articular cartilage, as this orientation is closely linked to cartilage mechanical functions. Using thermal-induced phase separation (TIPS) technology, we have fabricated an oriented cartilage extracellular matrix (ECM)-derived scaffold with a Young's modulus value 3 times higher than that of a random scaffold. In this study, we test the effectiveness of bone mesenchymal stem cell (BMSC)-scaffold constructs (cell-oriented and random) in repairing full-thickness articular cartilage defects in rabbits. While histological and immunohistochemical analyses revealed efficient cartilage regeneration and cartilaginous matrix secretion at 6 and 12 weeks after transplantation in both groups, the biochemical properties (levels of DNA, GAG, and collagen) and biomechanical values in the oriented scaffold group were higher than that in random group at early time points after implantation. While these differences were not evident at 24 weeks, the biochemical and biomechanical properties of the regenerated cartilage in the oriented scaffold-BMSC construct group were similar to that of native cartilage. These results demonstrate that an oriented scaffold, in combination with differentiated BMSCs can successfully repair full-thickness articular cartilage defects in rabbits, and produce cartilage enhanced biomechanical properties. PMID:26695629

  2. Biochemical analysis of normal articular cartilage in horses.

    PubMed

    Vachon, A M; Keeley, F W; McIlwraith, C W; Chapman, P

    1990-12-01

    Articular cartilage specimens from the distal articular surface of 32 radiocarpal bones from 24 2- to 5-year-old horses were analyzed. The total collagen content was determined on the basis of the 4-hydroxyproline content, using a colorimetric method. A method for estimating the proportions of types-I and -II collagen by measuring spectrophotometric densities of specific cyanogen bromide peptide bands from mixtures of types-I and -II collagen on sodium dodecyl sulfate-polyacrylamide gels was used. The cyanogen bromide peptides representative of each collagen types-I and -II were identified. The peptide ratios were then computed for each of several standards of type-I and -II mixtures. A standard curve was derived from the correlation between these ratios and the corresponding proportions of type-II collagen in standard mixtures. Galactosamine and glucosamine content (hexosamines) were measured by ion chromatography. The galactosamine-to-glucosamine ratio, chondroitin sulfate and keratan sulfate values, and total glycosaminoglycan content were derived from the measured hexosamine content. The total collagen content averaged 556 mg/g (55.6 mg/100 mg) of tissue (dry weight, [dw]). Type-II collagen was the major collagen type in normal articular cartilage specimens. The ratio of the area under the alpha 1 (II)CB10 peak to the area under the alpha 1 (I)CB 7,8 + alpha 1 (II)CB11 peak was a second-order polynomial function of the proportion of type-II collagen in the specimens. The mean galactosamine and glucosamine content were 20.6 mg/g and 7.9 mg/g (dw), respectively. The mean galactosamine-to-glucosamine ratio was 3.74 +/- 0.62.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2085215

  3. Adsorption and Distribution of Fluorescent Solutes near the Articular Surface of Mechanically Injured Cartilage

    PubMed Central

    Decker, Sarah G.A.; Moeini, Mohammad; Chin, Hooi Chuan; Rosenzweig, Derek H.; Quinn, Thomas M.

    2013-01-01

    The development of cartilage-specific imaging agents supports the improvement of tissue assessment by minimally invasive means. Techniques for highlighting cartilage surface damage in clinical images could provide for sensitive indications of posttraumatic injury and early stage osteoarthritis. Previous studies in our laboratory have demonstrated that fluorescent solutes interact with cartilage surfaces strongly enough to affect measurement of their partition coefficients within the tissue bulk. In this study, these findings were extended by examining solute adsorption and distribution near the articular surface of mechanically injured cartilage. Using viable cartilage explants injured by an established protocol, solute distributions near the articular surface of three commonly used fluorophores (fluorescein isothiocyanate (FITC), tetramethylrhodamine isothiocyanate (TRITC), and carboxytetramethylrhodamine (TAMRA)) were observed after absorption and subsequent desorption to assess solute-specific matrix interactions and reversibility. Both absorption and desorption processes demonstrated a trend of significantly less solute adsorption at surfaces of fissures compared to adjacent intact surfaces of damaged explants or surfaces of uninjured explants. After adsorption, normalized mean surface intensities of fissured surfaces of injured explants were 6%, 40%, and 32% for FITC, TRITC, and TAMRA, respectively, compared to uninjured surfaces. Similar values were found for sliced explants and after a desorption process. After desorption, a trend of increased solute adsorption at the site of intact damaged surfaces was noted (316% and 238% for injured and sliced explants exposed to FITC). Surface adsorption of solute was strongest for FITC and weakest for TAMRA; no solutes negatively affected cell viability. Results support the development of imaging agents that highlight distinct differences between fissured and intact cartilage surfaces. PMID:24268155

  4. Regeneration of articular cartilage using adipose stem cells.

    PubMed

    Im, Gun-Il

    2016-07-01

    Articular cartilage (AC) has limited potential for self-regeneration and damage to AC eventually leads to the development and progression of osteoarthritis (OA). Cell implantation strategies have emerged as a new treatment modality to regenerate AC. Adipose stem cells/adipose-derived stromal cells (ASCs) have gained attention due to their abundance, excellent proliferative potential, and minimal morbidity during harvest. These advantages lower the cost of cell therapy by circumventing time-consuming procedure of culture expansion. ASCs have drawn attention as a potential source for cartilage regeneration since the feasibility of chondrogenesis from ASCs was first reported. After several groups reported inferior chondrogenesis from ASCs, numerous methods were devised to overcome the intrinsic properties. Most in vivo animal studies have reported good results using predifferentiated or undifferentiated, autologous or allogeneic ASCs to regenerate cartilage in osteochondral defects or surgically-induced OA. In this review, we summarize literature on the isolation and in vitro differentiation processes of ASCs, in vivo studies to regenerate AC in osteochondral defects and OA using ASCs, and clinical applications of ASCs. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1830-1844, 2016. PMID:26990234

  5. Tribology approach to the engineering and study of articular cartilage.

    PubMed

    Wimmer, Markus A; Grad, Sibylle; Kaup, Thomas; Hänni, Markus; Schneider, Erich; Gogolewski, Sylwester; Alini, Mauro

    2004-01-01

    This study has been based on the assumption that articular motion is an important aspect of mechanotransduction in synovial joints. For this reason a new bioreactor concept, able to reproduce joint kinematics more closely, has been designed. The prototype consists of a rotating scaffold and/or cartilage pin, which is pressed onto an orthogonally rotating ball. By oscillating pin and ball in phase difference, elliptical displacement trajectories are generated that are similar to the motion paths occurring in vivo. Simultaneously, dynamic compression may be applied with a linear actuator, while two-step-motors generate the rotation of pin and ball. The whole apparatus is placed in an incubator. The control station is located outside. Preliminary investigations at the gene expression level demonstrated promising results. Compared with free-swelling control and/or simply compression-loaded samples, chondrocyte-seeded scaffolds as well as nasal cartilage explants exposed to interface motion both showed elevated levels of cartilage oligomeric matrix protein mRNA. The final design of the bioreactor will include four individual stations in line, which will facilitate the investigation of motion-initiated effects at the contacting surfaces in more detail. PMID:15588403

  6. Characterization of neopeptides in equine articular cartilage degradation.

    PubMed

    Peffers, Mandy Jayne; Thornton, David James; Clegg, Peter David

    2016-01-01

    Osteoarthritis is characterized by a loss of extracellular matrix that leads to cartilage degradation and joint space narrowing. Specific proteases, including the aggrecanases ADAMTS-4 and matrix metalloproteinase 3, are important in initiating and promoting cartilage degradation in osteoarthritis. This study investigated protease-specific and disease-specific cleavage patterns of particular extracellular matrix proteins by comparing new peptide fragments, neopeptides, in specific exogenous protease-driven digestion of a crude cartilage proteoglycan extract and an in-vitro model of early osteoarthritis. Additionally, equine cartilage explants were treated with interleukin-1 and the media collected. Proteolytic cleavage products following trypsin digestion were then identified using tandem mass spectrometry. Complete sequences of proteolytically cleaved neopeptides were determined for the major cartilage proteoglycans aggrecan, biglycan, decorin, fibromodulin plus cartilage oligomeric matrix protein. The generation of neopeptides varied with enzyme specificity; however, some peptides were common to all samples. Previous known and novel cleavage sites were identifies. The identification of novel peptide fragments provides a platform for the development of antibodies that could assist in the identification of biomarkers for osteoarthritis (OA), as well as the identification of basic biochemical processes underlying OA. PMID:26124002

  7. Nanomechanical phenotype of chondroadherin-null murine articular cartilage.

    PubMed

    Batista, Michael A; Nia, Hadi T; Önnerfjord, Patrik; Cox, Karen A; Ortiz, Christine; Grodzinsky, Alan J; Heinegård, Dick; Han, Lin

    2014-09-01

    Chondroadherin (CHAD), a class IV small leucine rich proteoglycan/protein (SLRP), was hypothesized to play important roles in regulating chondrocyte signaling and cartilage homeostasis. However, its roles in cartilage development and function are not well understood, and no major osteoarthritis-like phenotype was found in the murine model with CHAD genetically deleted (CHAD(-/-)). In this study, we used atomic force microscopy (AFM)-based nanoindentation to quantify the effects of CHAD deletion on changes in the biomechanical function of murine cartilage. In comparison to wild-type (WT) mice, CHAD-deletion resulted in a significant ≈70-80% reduction in the indentation modulus, Eind, of the superficial zone knee cartilage of 11 weeks, 4 months and 1 year old animals. This mechanical phenotype correlates well with observed increases in the heterogeneity collagen fibril diameters in the surface zone. The results suggest that CHAD mainly plays a major role in regulating the formation of the collagen fibrillar network during the early skeletal development. In contrast, CHAD-deletion had no appreciable effects on the indentation mechanics of middle/deep zone cartilage, likely due to the dominating role of aggrecan in the middle/deep zone. The presence of significant rate dependence of the indentation stiffness in both WT and CHAD(-/-) knee cartilage suggested the importance of both fluid flow induced poroelasticity and intrinsic viscoelasticity in murine cartilage biomechanical properties. Furthermore, the marked differences in the nanomechanical behavior of WT versus CHAD(-/-) cartilage contrasted sharply with the relative absence of overt differences in histological appearance. These observations highlight the sensitivity of nanomechanical tools in evaluating structural and mechanical phenotypes in transgenic mice. PMID:24892719

  8. Amino acid racemization reveals differential protein turnover in osteoarthritic articular and meniscal cartilages

    PubMed Central

    Stabler, Thomas V; Byers, Samuel S; Zura, Robert D; Kraus, Virginia Byers

    2009-01-01

    Introduction Certain amino acids within proteins have been reported to change from the L form to the D form over time. This process is known as racemization and is most likely to occur in long-lived low-turnover tissues such as normal cartilage. We hypothesized that diseased tissue, as found in an osteoarthritic (OA) joint, would have increased turnover reflected by a decrease in the racemized amino acid content. Methods Using high-performance liquid chromatography methods, we quantified the L and D forms of amino acids reported to racemize in vivo on a biological timescale: alanine, aspartate (Asp), asparagine (Asn), glutamate, glutamine, isoleucine, leucine (Leu), and serine (Ser). Furthermore, using a metabolically inactive control material (tooth dentin) and a control material with normal metabolism (normal articular cartilage), we developed an age adjustment in order to make inferences about the state of protein turnover in cartilage and meniscus. Results In the metabolically inactive control material (n = 25, ages 13 to 80 years) and the normal metabolizing control material (n = 19, ages 17 to 83 years), only Asp + Asn (Asx), Ser, and Leu showed a significant change (increase) in racemization with age (P < 0.01). The age-adjusted proportions of racemized to total amino acid (D/D+L expressed as a percentage of the control material) for Asx, Ser, and Leu when compared with the normal articular cartilage control were 97%, 74%, and 73% in OA meniscal cartilage and 97%, 70%, and 78% in OA articular cartilage. We also observed lower amino acid content in OA articular and meniscal cartilages compared with normal articular cartilage as well as a loss of total amino acids with age in the OA meniscal but not the OA articular cartilage. Conclusions These data demonstrate comparable anabolic responses for non-lesioned OA articular cartilage and OA meniscal cartilage but an excess of catabolism over anabolism for the meniscal cartilage. PMID:19267899

  9. Tissue-Engineered Articular Cartilage Exhibits Tension-Compression Nonlinearity Reminiscent of the Native Cartilage

    PubMed Central

    Kelly, Terri-Ann N.; Roach, Brendan L.; Weidner, Zachary D.; Mackenzie-Smith, Charles R.; O'Connell, Grace D.; Lima, Eric G.; Stoker, Aaron M.; Cook, James L.; Ateshian, Gerard A.; Hung, Clark T.

    2013-01-01

    The tensile modulus of articular cartilage is much larger than its compressive modulus. This tension-compression nonlinearity enhances interstitial fluid pressurization and decreases the frictional coefficient. The current set of studies examines the tensile and compressive properties of cylindrical chondrocyte-seeded agarose constructs over different developmental stages through a novel method that combines osmotic loading, video microscopy, and uniaxial unconfined compression testing. This method was previously used to examine tension-compression nonlinearity in native cartilage. Engineered cartilage, cultured under free-swelling (FS) or dynamically loaded (DL) conditions, was tested in unconfined compression in hypertonic and hypotonic salt solutions. The apparent equilibrium modulus decreased with increasing salt concentration, indicating that increasing the bath solution osmolarity shielded the fixed charges within the tissue, shifting the measured moduli along the tension-compression curve and revealing the intrinsic properties of the tissue. With this method, we were able to measure the tensile (401±83 kPa for FS and 678±473 kPa for DL) and compressive (161±33 kPa for FS and 348±203 kPa for DL) moduli of the same engineered cartilage specimens. These moduli are comparable to values obtained from traditional methods, validating this technique for measuring the tensile and compressive properties of hydrogel-based constructs. This study shows that engineered cartilage exhibits tension-compression nonlinearity reminiscent of the native tissue, and that dynamic deformational loading can yield significantly higher tensile properties. PMID:23791084

  10. Elastin fibers display a versatile microfibril network in articular cartilage depending on the mechanical microenvironments.

    PubMed

    He, Bo; Wu, Jian Ping; Chen, Hong Hui; Kirk, Thomas Brett; Xu, Jiake

    2013-09-01

    Elastin fibers are major extracellular matrix macromolecules that are critical in maintaining the elasticity and resilience of tissues such as blood vessels, lungs and skins. However, the role of elastin in articular cartilage is poorly defined. The present study investigated the organization of elastin fiber in articular cartilage, its relationship to collagen fibers and the architecture of elastin fibers from different mechanical environments by using a kangaroo model. Five morphologies of elastin fibers were identified: Straight fiber, straight fiber with branches, branching fibers directly associated with chondrocyte, wave fiber and fine elastin. The architecture of the elastin network varied significantly with cartilage depth. In the most superficial layer of tibial plateau articular cartilage, dense elastin fibers formed a distinctive cobweb-like meshwork which was parallel to the cartilage surface. In the superficial zone, elastin fibers were well organized in a preferred orientation which was parallel to collagen fibers. In the deep zone, no detectable elastin fiber was found. Moreover, differences in the organization of elastin fibers were also observed between articular cartilage from the tibial plateau, femoral condyle, and distal humerus. This study unravels the detailed microarchitecture of elastin fibers which display a well-organized three-dimensional versatile network in articular cartilage. Our findings imply that elastin fibers may play a crucial role in maintaining the integrity, elasticity, and the mechanical properties of articular cartilage, and that the local mechanical environment affects the architectural development of elastin fibers. PMID:23649803

  11. Mesenchymal stem cells can survive on the extracellular matrix-derived decellularized bovine articular cartilage scaffold

    PubMed Central

    Tavassoli, Amin; Matin, Maryam Moghaddam; Niaki, Malihe Akbarzade; Mahdavi-Shahri, Nasser; Shahabipour, Fahimeh

    2015-01-01

    Objective (s): The scarcity of articular cartilage defect to repair due to absence of blood vessels and tissue engineering is one of the promising approaches for cartilage regeneration. The objective of this study was to prepare an extracellular matrix derived decellularized bovine articular cartilage scaffold and investigate its interactions with seeded rat bone marrow mesenchymal stem cells (BM-MSCs). Materials and Methods: Bovine articular cartilage that was cut into pieces with 2 mm thickness, were decellularized by combination of physical and chemical methods including snap freeze-thaw and treatment with sodium dodecyl sulfate (SDS). The scaffolds were then seeded with 1, 1’-dioctadecyl-3, 3, 3’, 3’-tetramethylindocarbocyanine perchlorate (DiI) labeled BM-MSCs and cultured for up to two weeks. Results: Histological studies of decellularized bovine articular cartilage showed that using 5 cycles of snap freeze-thaw in liquid nitrogen and treatment with 2.5% SDS for 4 hr led to the best decellularization, while preserving the articular cartilage structure. Adherence and penetration of seeded BM-MSCs on to the scaffold were displayed by histological and florescence examinations and also confirmed by electron microscopy. Conclusion: ECM-derived decellularized articular cartilage scaffold provides a suitable environment to support adhesion and maintenance of cultured BM-MSCs and could be applied to investigate cellular behaviors in this system and may also be useful for studies of cartilage tissue engineering. PMID:26877852

  12. Chondrocyte survival in articular cartilage: the influence of subchondral bone in a bovine model.

    PubMed

    Amin, A K; Huntley, J S; Simpson, A H R W; Hall, A C

    2009-05-01

    The aim of this study was to determine whether subchondral bone influences in situ chondrocyte survival. Bovine explants were cultured in serum-free media over seven days with subchondral bone excised from articular cartilage (group A), subchondral bone left attached to articular cartilage (group B), and subchondral bone excised but co-cultured with articular cartilage (group C). Using confocal laser scanning microscopy, fluorescent probes and biochemical assays, in situ chondrocyte viability and relevant biophysical parameters (cartilage thickness, cell density, culture medium composition) were quantified over time (2.5 hours vs seven days). There was a significant increase in chondrocyte death over seven days, primarily within the superficial zone, for group A, but not for groups B or C (p < 0.05). There was no significant difference in cartilage thickness or cell density between groups A, B and C (p > 0.05). Increases in the protein content of the culture media for groups B and C, but not for group A, suggested that the release of soluble factors from subchondral bone may have influenced chondrocyte survival. In conclusion, subchondral bone significantly influenced chondrocyte survival in articular cartilage during explant culture. The extrapolation of bone-cartilage interactions in vitro to the clinical situation must be made with caution, but the findings from these experiments suggest that future investigation into in vivo mechanisms of articular cartilage survival and degradation must consider the interactions of cartilage with subchondral bone. PMID:19407309

  13. Gene Expression Profiling Reveals Similarities between the Spatial Architectures of Postnatal Articular and Growth Plate Cartilage

    PubMed Central

    Chau, Michael; Lui, Julian C.; Landman, Ellie B. M.; Späth, Stephan-Stanislaw; Vortkamp, Andrea; Baron, Jeffrey; Nilsson, Ola

    2014-01-01

    Articular and growth plate cartilage are discrete tissues but arise from a common cartilaginous condensation and have comparable spatial architectures consisting of distinct layers of chondrocytes. To investigate similarities and differences between articular and growth plate cartilage and to explore transcriptional changes that occur during the onset of their divergence, we performed manual microdissection of 10-day-old rat proximal tibias, microarray analysis, bioinformatics, and real-time PCR to compare gene expression profiles in individual cartilage layers. We found that many genes that were spatially upregulated in the intermediate/deep zone of articular cartilage were also spatially upregulated in the resting zone of growth plate cartilage (overlap greater than expected by chance, P<0.001). Interestingly, the superficial zone of articular cartilage showed an expression profile with similarities to both the proliferative and hypertrophic zones of growth plate cartilage (P<0.001 each). Additionally, significant numbers of known proliferative zone markers (3 out of 6) and hypertrophic zone markers (27 out of 126) were spatially upregulated in the superficial zone (more than expected by chance, P<0.001 each). In conclusion, we provide evidence that the intermediate/deep zone of articular cartilage has a gene expression profile more similar to that of the resting zone of growth plate cartilage, whereas the superficial zone has a gene expression profile more similar to those of the proliferative and hypertrophic zones. These findings suggest that the superficial zone chondrocytes of articular cartilage differentiate according to a program that is not completely different from but instead has distinct similarities to the hypertrophic differentiation program of growth plate chondrocytes. We also present functional signaling pathways implicated by differential gene expression between articular and growth plate cartilage during their initial separation by the

  14. Radiofrequency (electrosurgical) ablation of articular cartilage: a study in sheep.

    PubMed

    Turner, A S; Tippett, J W; Powers, B E; Dewell, R D; Mallinckrodt, C H

    1998-09-01

    The objective of this study was to examine the effect of a bipolar ablation probe on experimentally roughened articular cartilage and compare it with the traditional mechanical shaving technique using the knee joint of sheep. Twenty-eight skeletally mature ewes were divided randomly into two groups: one group was treated with a rotating shaving device and another group was treated using the bipolar ablation probe (Bipolar Arthroscopic Probe; Electroscope, Inc, Boulder, CO). Animals were killed at 0, 6, 12, and 24 weeks, and histological sections of the experimental limbs were compared with sections of the opposite limb using a modified Mankin scale. The following variables were used to determine scores: surface (0-6), cells (0-4), hypocellularity (0-3), matrix staining (transitional zone [0-4], radiate zone [0-4], and focal empty lacunae or hypereosinophilic cells (0-3). Differences in scores for all response variables were calculated as treated limb minus sham limb. Response variables were formed: score >0 recoded as 1 (favorable response treated better than sham), score of 0 recoded as 2 (neutral response no differences), and score <0 recoded as 3 (unfavorable response treated worse than sham). Bipolar ablative probe-treated limbs had 14.29% favorable responses and 35.71% favorable or neutral responses, whereas shave-treated limbs had 0% favorable and only 7.14% favorable or neutral responses. For all variables, bipolar ablative probe-treated limbs had more favorable responses. The less severe histological change in the bipolar ablative probe-treated joints compared with the shave-treated joints suggests that bipolar ablation of articular cartilage may be a better treatment for chondromalacia than the usual shaving methods of debridement. Further, there were no pathological changes in the subchondral bone. PMID:9754476

  15. Repair of articular cartilage in rabbit osteochondral defects promoted by extracorporeal shock wave therapy

    NASA Astrophysics Data System (ADS)

    Chu, C.-H.; Yen, Y.-S.; Chen, P.-L.; Wen, C.-Y.

    2015-03-01

    This study investigated the stimulative effect of extracorporeal shock wave therapy (ESWT) on the articular cartilage regeneration in the rabbit osteochondral defect model for the first time. An osteochondral defect, 3 mm in diameter and 3 mm in depth, was drilled in the patellar groove at the distal end of each femur in 24 mature New Zealand rabbits. The right patellar defects received 500 impulses of shock waves of (at 14 kV) at 1 week after surgery and were designated as the experimental samples; the left patellar defects served as control. At 4, 8, and 12 weeks after ESWT, cartilage repair was evaluated macroscopically and histologically using a semiquantitative grading scale. The total scores of the macroscopic evaluation at 4, 8, and 12 weeks in the experimental group were superior to those in the control group (statistical significance level ). As to the total scores of the histologic evaluation, the experimental group showed a tendency toward a better recovery than the control group at 4 weeks (). At 8 and 12 weeks the differences between the experimental and control groups became mild and had no significance on statistical analysis. These findings suggested that regeneration of articular cartilage defects might be promoted by ESWT, especially at the early stage. The easy and safe ESWT is potentially viable for clinical application.

  16. Prenatal caffeine exposure induces a poor quality of articular cartilage in male adult offspring rats via cholesterol accumulation in cartilage

    PubMed Central

    Luo, Hanwen; Li, Jing; Cao, Hong; Tan, Yang; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2015-01-01

    Epidemiological investigations indicate that osteoarthritis is associated with intrauterine growth retardation (IUGR) and abnormal cholesterol metabolism. Our previous studies showed that prenatal caffeine exposure (PCE) induced chondrogenesis retardation in IUGR offspring rats. The current study sought to investigate the effects of PCE on male IUGR offspring rats’ articular cartilage, and the mechanisms associated with abnormal cholesterol metabolism. Based on the results from both male fetal and adult fed a high-fat diet (HFD) studies of rats that experienced PCE (120 mg/kg.d), the results showed a poor quality of articular cartilage and cholesterol accumulation in the adult PCE group. Meanwhile, the serum total cholesterol and low-density lipoprotein-cholesterol concentrations were increased in adult PCE offspring. We also observed lower expression of insulin-like growth factor1 (IGF1) and impaired cholesterol efflux in adult articular cartilage. Furthermore, the expression of cartilage functional genes, components of the IGF1 signaling pathway and cholesterol efflux pathway related genes were decreased in PCE fetal cartilage. In conclusion, PCE induced a poor quality of articular cartilage in male adult offspring fed a HFD. This finding was shown to be due to cholesterol accumulation in the cartilage, which may have resulted from intrauterine reduced activity of the IGF1 signaling pathway. PMID:26639318

  17. An ultrasound biomicroscopic and water jet ultrasound indentation method for detecting the degenerative changes of articular cartilage in a rabbit model of progressive osteoarthritis.

    PubMed

    Wang, Yuexiang; Huang, Yan-Ping; Liu, Aijun; Wan, Wenbo; Zheng, Yong-Ping

    2014-06-01

    It is important to assess the early degeneration of articular cartilage associated with osteoarthritis (OA) for early intervention and treatment planning. Previously, we have developed a high frequency ultrasound and water jet indentation method for the morphologic, acoustic and mechanical assessment of articular cartilage, using the enzymatic digestion as a model of osteoarthritic degeneration. No naturally degenerated articular cartilage has been tested with the developed method. In this study, we aimed to determine the usefulness of the developed method for detecting the natural degeneration of articular cartilage in a standard surgical model of OA in rabbits. Forty adult New Zealand white female rabbits were used in this study, which included 30 experimental rabbits undergoing the right anterior cruciate ligament transection surgery and 10 control rabbits. At the 3rd, 6th, and 9th week post-surgery, 10 experimental rabbits were sacrificed, respectively, for assessment of the knee cartilage quality. The cartilage at the medial and lateral femoral condyles and tibial plateaus (four points) was measured by the high frequency ultrasound biomicroscopy, the water jet ultrasound indentation and a contact mechanical indentation test before a histopathologic analysis for grading of degeneration severity. Measured parameters were compared among different groups classified either by post-surgery time or by histopathologic grade. The results showed a general trend of increase for ultrasound roughness index and a general trend of decrease for integrated reflection coefficient, stiffness coefficient from water-jet indentation and Young's modulus (E) from the mechanical indentation with the increase of post-surgery time. Comparisons among groups with different histopathologic grades showed similar trend with the increase of degeneration severity. The water jet ultrasound indentation method was demonstrated to be an effective method to measure the mechanical properties of the

  18. Patterns of radiocarpal joint articular cartilage wear in cadavers.

    PubMed

    Gorniak, Gerard C; Conrad, Will; Conrad, Erin; Decker, Bonnie

    2012-05-01

    The radiocarpal joint transmits about 80% of the compression forces crossing the wrist. However, primary osteoarthritis of this joint is surprisingly uncommon, suggesting that articular cartilage wear is not sufficient to produce arthritic symptoms. By examining the distal radius, scaphoid, and lunate in aged cadavers, wear patterns were charted and measured, allowing assessment of radiocarpal joint wear and mechanics. Bilateral radiocarpal joints of 16 females and 14 males (age 77.7 ± 14.4, N = 30) were exposed and measurements of the wear recorded microscopically. Wear locations were mapped, and X-Y loci and wear areas calculated. Gender right and sides compared. Over 95% of distal radius wear showed distinct radial-scaphoid and radial-lunate wear areas. These bilateral areas were in the palmar half of the distal radius. One main central wear area was seen in 95% of the scaphoid, and 97% of the lunate articular surfaces that were examined. Articular wear showed a circular pattern and was minimal in 95.7% of the surfaces, and the lunate showed the largest wear area. Wear patterns in males and females support the literature that for most ADLs the wrist is in slight extension and ulnar deviation. There are gender differences, but wear areas between sides were similar. Female wear indicates their wrist is positioned more often in a more extended and ulnarly deviated position than males. The wear patterns suggest rotational movements of the scaphoid and lunate during wrist motion and that the wrist is most often used in neutral flexion/extension to slight extension. PMID:22095798

  19. Effects of salicylates and other nonsteroidal anti-inflammatory drugs on articular cartilage.

    PubMed

    Brandt, K D; Palmoski, M J

    1984-07-13

    According to in vivo experimental data, salicylates and several other nonsteroidal anti-inflammatory agents suppress proteoglycan biosynthesis in normal and degenerating articular cartilage. Therapeutic levels of aspirin in vivo had a similar adverse effect on degenerating cartilage, as noted in two canine models of osteoarthritis and cartilage atrophy. Because the effective daily antirheumatic dose of nonsteroidal anti-inflammatory drugs is lower than that of salicylates, these drugs may have less negative effects on degenerating articular cartilage. However, clinical significance cannot be extrapolated from these experimental data. PMID:6465163

  20. Time-dependent processes in stem cell-based tissue engineering of articular cartilage

    PubMed Central

    Gadjanski, Ivana; Spiller, Kara; Vunjak-Novakovic, Gordana

    2012-01-01

    Articular cartilage (AC), situated in diarthrodial joints at the end of the long bones, is composed of a single cell type (chondrocytes) embedded in dense extracellular matrix comprised of collagens and proteoglycans. AC is avascular and alymphatic and is not innervated. At first glance, such a seemingly simple tissue appears to be an easy target for the rapidly developing field of tissue engineering. However, cartilage engineering has proven to be very challenging. We focus on time-dependent processes associated with the development of native cartilage starting from stem cells, and the modalities for utilizing these processes for tissue engineering of articular cartilage. PMID:22016073

  1. Imaging articular cartilage using second harmonic generation microscopy

    NASA Astrophysics Data System (ADS)

    Mansfield, Jessica C.; Winlove, C. Peter; Knapp, Karen; Matcher, Stephen J.

    2006-02-01

    Sub cellular resolution images of equine articular cartilage have been obtained using both second harmonic generation microscopy (SHGM) and two-photon fluorescence microscopy (TPFM). The SHGM images clearly map the distribution of the collagen II fibers within the extracellular matrix while the TPFM images show the distribution of endogenous two-photon fluorophores in both the cells and the extracellular matrix, highlighting especially the pericellular matrix and bright 2-3μm diameter features within the cells. To investigate the source of TPF in the extracellular matrix experiments have been carried out to see if it may originate from the proteoglycans. Pure solutions of the following proteoglycans hyaluronan, chondroitin sulfate and aggrecan have been imaged, only the aggrecan produced any TPF and here the intensity was not great enough to account for the TPF in the extracellular matrix. Also cartilage samples were subjected to a process to remove proteoglycans and cellular components. After this process the TPF from the samples had decreased by a factor of two, with respect to the SHG intensity.

  2. 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

  3. Multi-parametric MRI characterization of enzymatically degraded articular cartilage.

    PubMed

    Nissi, Mikko J; Salo, Elli-Noora; Tiitu, Virpi; Liimatainen, Timo; Michaeli, Shalom; Mangia, Silvia; Ellermann, Jutta; Nieminen, Miika T

    2016-07-01

    Several laboratory and rotating frame quantitative MRI parameters were evaluated and compared for detection of changes in articular cartilage following selective enzymatic digestion. Bovine osteochondral specimens were subjected to 44 h incubation in control medium or in collagenase or chondroitinase ABC to induce superficial collagen or proteoglycan (glycosaminoglycan) alterations. The samples were scanned at 9.4 T for T1 , T1 Gd (dGEMRIC), T2 , adiabatic T1 ρ , adiabatic T2 ρ , continuous-wave T1 ρ , TRAFF2 , and T1 sat relaxation times and for magnetization transfer ratio (MTR). For reference, glycosaminoglycan content, collagen fibril orientation and biomechanical properties were determined. Changes primarily in the superficial cartilage were noted after enzymatic degradation. Most of the studied parameters were sensitive to the destruction of collagen network, whereas glycosaminoglycan depletion was detected only by native T1 and T1 Gd relaxation time constants throughout the tissue and by MTR superficially. T1 , adiabatic T1 ρ , adiabatic T2 ρ , continuous-wave T1 ρ , and T1 sat correlated significantly with the biomechanical properties while T1 Gd correlated with glycosaminoglycan staining. The findings indicated that most of the studied MRI parameters were sensitive to both glycosaminoglycan content and collagen network integrity, with changes due to enzymatic treatment detected primarily in the superficial tissue. Strong correlation of T1 , adiabatic T1ρ , adiabatic T2 ρ , continuous-wave T1 ρ , and T1 sat with the altered biomechanical properties, reflects that these parameters were sensitive to critical functional properties of cartilage. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1111-1120, 2016. PMID:26662555

  4. Winner of the 1996 Cabaud Award. The effect of lifelong exercise on canine articular cartilage.

    PubMed

    Newton, P M; Mow, V C; Gardner, T R; Buckwalter, J A; Albright, J P

    1997-01-01

    The effect of long-term exercise on canine knees was studied to determine whether an increased level of lifelong weightbearing exercise causes degeneration, or changes that may lead to degeneration, of articular cartilage. Eleven dogs were exercised on a treadmill at 3 km/hr for 75 minutes 5 days a week for 527 weeks while carrying jackets weighing 130% of their body weight. Ten control dogs were allowed unrestricted activity in cages for the 550 weeks. At the completion of the study all knee joints were inspected for evidence of joint injury and degeneration. Articular cartilage surfaces from the medial tibial plateau were examined by light microscopy, the cartilage thickness was measured, and the intrinsic material properties were determined by mechanical testing. No joints had ligament or meniscal injuries, cartilage erosions, or osteophytes. Light microscopy did not demonstrate cartilage fibrillation or differences in safranin O staining of the tibial articular cartilages between the two groups. Furthermore, the tibial articular cartilage thickness and mechanical properties did not differ between the two groups. These results show that a lifetime of regular weightbearing exercise in dogs with normal joints did not cause alterations in the structure and mechanical properties of articular cartilage that might lead to joint degeneration. PMID:9167804

  5. Matrix metalloproteinase-3 in articular cartilage is upregulated by joint immobilization and suppressed by passive joint motion.

    PubMed

    Leong, Daniel J; Gu, Xiang I; Li, Yonghui; Lee, Jonathan Y; Laudier, Damien M; Majeska, Robert J; Schaffler, Mitchell B; Cardoso, Luis; Sun, Hui B

    2010-06-01

    Both underloading and overloading of joints can lead to articular cartilage degradation, a process mediated in part by matrix metalloproteinases (MMPs). Here we examine the effects of reduced loading of rat hindlimbs on articular cartilage expression of MMP-3, which not only digests matrix components but also activates other proteolytic enzymes. We show that hindlimb immobilization resulted in elevated MMP-3 mRNA expression at 6h that was sustained throughout the 21day immobilization period. MMP-3 upregulation was higher in the medial condyle than the lateral, and was greatest in the superficial cartilage zone, followed by middle and deep zones. These areas also showed decreases in safranin O staining, consistent with reduced cartilage proteoglycan content, as early as 7days after immobilization. One hour of daily moderate mechanical loading, applied as passive joint motion, reduced the MMP-3 and ADAMTS-5 increases that resulted from immobilization, and also prevented changes in safranin O staining. Intra-articular injections of an MMP-3 inhibitor, N-isobutyl-N-(4-methoxyphenylsulfonyl)-glycylhydroxamic acid (NNGH), dampened the catabolic effects of a 7day immobilization period, indicating a likely requirement for MMP-3 in the regulation of proteoglycan levels through ADAMTS-5. These results suggest that biomechanical forces have the potential to combat cartilage destruction and can be critical in developing effective therapeutic strategies. PMID:20153826

  6. Matrix Metalloproteinase-3 In Articular Cartilage Is Upregulated By Joint Immobilization And Suppressed By Passive Joint Motion

    PubMed Central

    Leong, Daniel J; Gu, Xiang I; Li, Yonghui; Lee, Jonathan Y; Laudier, Damien M; Majeska, Robert J; Schaffler, Mitchell B; Cardoso, Luis; Sun, Hui B.

    2010-01-01

    Both underloading and overloading of joints can lead to articular cartilage degradation, a process mediated in part by matrix metalloproteinases (MMPs). Here we examine the effects of reduced loading of rat hindlimbs on articular cartilage expression of MMP-3, which not only digests matrix components but also activates other proteolytic enzymes. We show that hindlimb immobilization resulted in elevated MMP-3 mRNA expression at 6 hours that was sustained throughout the 21 day immobilization period. MMP-3 upregulation was higher in the medial condyle than the lateral, and was greatest in the superficial cartilage zone, followed by middle and deep zones. These areas also showed decreases in safranin O staining, consistent with reduced cartilage proteoglycan content, as early as 7 days after immobilization. One hour of daily moderate mechanical loading, applied as passive joint motion, reduced the MMP-3 and ADAMTS-5 increases that resulted from immobilization, and also prevented changes in safranin O staining. Intra-articular injections of an MMP-3 inhibitor, N-isobutyl-N-(4-methoxyphenylsulfonyl)-glycylhydroxamic acid (NNGH), dampened the catabolic effects of a 7 day immobilization period, indicating a likely requirement for MMP-3 in the regulation of proteoglycan levels through ADAMTS-5. These results suggest that biomechanical forces have the potential to combat cartilage destruction and can be critical in developing effective therapeutic strategies. PMID:20153826

  7. Repair of articular cartilage defects in rabbits through tissue-engineered cartilage constructed with chitosan hydrogel and chondrocytes*

    PubMed Central

    ZHAO, Ming; CHEN, Zhu; LIU, Kang; WAN, Yu-qing; LI, Xu-dong; Luo, Xu-wei; Bai, Yi-guang; Yang, Ze-long; Feng, Gang

    2015-01-01

    Objective: In our previous work, we prepared a type of chitosan hydrogel with excellent biocompatibility. In this study, tissue-engineered cartilage constructed with this chitosan hydrogel and costal chondrocytes was used to repair the articular cartilage defects. Methods: Chitosan hydrogels were prepared with a crosslinker formed by combining 1,6-diisocyanatohexane and polyethylene glycol. Chitosan hydrogel scaffold was seeded with rabbit chondrocytes that had been cultured for one week in vitro to form the preliminary tissue-engineered cartilage. This preliminary tissue-engineered cartilage was then transplanted into the defective rabbit articular cartilage. There were three treatment groups: the experimental group received preliminary tissue-engineered cartilage; the blank group received pure chitosan hydrogels; and, the control group had received no implantation. The knee joints were harvested at predetermined time. The repaired cartilage was analyzed through gross morphology, histologically and immunohistochemically. The repairs were scored according to the international cartilage repair society (ICRS) standard. Results: The gross morphology results suggested that the defects were repaired completely in the experimental group after twelve weeks. The regenerated tissue connected closely with subchondral bone and the boundary with normal tissue was fuzzy. The cartilage lacuna in the regenerated tissue was similar to normal cartilage lacuna. The results of ICRS gross and histological grading showed that there were significant differences among the three groups (P<0.05). Conclusions: Chondrocytes implanted in the scaffold can adhere, proliferate, and secrete extracellular matrix. The novel tissue-engineered cartilage constructed in our research can completely repair the structure of damaged articular cartilage. PMID:26537209

  8. In vitro growth factor-induced bio engineering of mature articular cartilage

    PubMed Central

    Khan, Ilyas M.; Francis, Lewis; Theobald, Peter S.; Perni, Stefano; Young, Robert D.; Prokopovich, Polina; Conlan, R. Steven; Archer, Charles W.

    2013-01-01

    Articular cartilage maturation is the postnatal development process that adapts joint surfaces to their site-specific biomechanical demands. Maturation involves gross morphological changes that occur through a process of synchronised growth and resorption of cartilage and generally ends at sexual maturity. The inability to induce maturation in biomaterial constructs designed for cartilage repair has been cited as a major cause for their failure in producing persistent cell-based repair of joint lesions. The combination of growth factors FGF2 and TGFβ1 induces accelerated articular cartilage maturation in vitro such that many molecular and morphological characteristics of tissue maturation are observable. We hypothesised that experimental growth factor-induced maturation of immature cartilage would result in a biophysical and biochemical composition consistent with a mature phenotype. Using native immature and mature cartilage as reference, we observed that growth factor-treated immature cartilages displayed increased nano-compressive stiffness, decreased surface adhesion, decreased water content, increased collagen content and smoother surfaces, correlating with a convergence to the mature cartilage phenotype. Furthermore, increased gene expression of surface structural protein collagen type I in growth factor-treated explants compared to reference cartilages demonstrates that they are still in the dynamic phase of the postnatal developmental transition. These data provide a basis for understanding the regulation of postnatal maturation of articular cartilage and the application of growth factor-induced maturation in vitro and in vivo in order to repair and regenerate cartilage defects. PMID:23182922

  9. Comprehensive Genome-Wide Transcriptomic Analysis of Immature Articular Cartilage following Ischemic Osteonecrosis of the Femoral Head in Piglets

    PubMed Central

    Adapala, Naga Suresh; Kim, Harry K. W.

    2016-01-01

    Objective Ischemic osteonecrosis of the femoral head (ONFH) in piglets results in an ischemic injury to the immature articular cartilage. The molecular changes in the articular cartilage in response to ONFH have not been investigated using a transcriptomic approach. The purpose of this study was to perform a genome-wide transcriptomic analysis to identify genes that are upregulated in the immature articular cartilage following ONFH. Methods ONFH was induced in the right femoral head of 6-week old piglets. The unoperated femoral head was used as the normal control. At 24 hours (acute ischemic-hypoxic injury), 2 weeks (avascular necrosis in the femoral head) and 4 weeks (early repair) after surgery (n = 4 piglets/time point), RNA was isolated from the articular cartilage of the femoral head. A microarray analysis was performed using Affymetrix Porcine GeneChip Array. An enrichment analysis and functional clustering of the genes upregulated due to ONFH were performed using DAVID and STRING software, respectively. The increased expression of selected genes was confirmed by a real-time qRTPCR analysis. Results Induction of ONFH resulted in the upregulation of 383 genes at 24 hours, 122 genes at 2 weeks and 124 genes at 4 weeks compared to the normal controls. At 24 hours, the genes involved in oxidoreductive, cell-survival, and angiogenic responses were significantly enriched among the upregulated genes. These genes were involved in HIF-1, PI3K-Akt, and MAPK signaling pathways. At 2 weeks, secretory and signaling proteins involved in angiogenic and inflammatory responses, PI3K-Akt and matrix-remodeling pathways were significantly enriched. At 4 weeks, genes that represent inflammatory cytokines and chemokine signaling pathways were significantly enriched. Several index genes (genes that are upregulated at more than one time point following ONFH and are known to be important in various biological processes) including HIF-1A, VEGFA, IL-6, IL6R, IL-8, CCL2, FGF2, TGFB2

  10. Intra-articular injection of Torin 1 reduces degeneration of articular cartilage in a rabbit osteoarthritis model

    PubMed Central

    Cheng, N-T.; Cui, Y-P.

    2016-01-01

    Objectives Recent studies have shown that systemic injection of rapamycin can prevent the development of osteoarthritis (OA)-like changes in human chondrocytes and reduce the severity of experimental OA. However, the systemic injection of rapamycin leads to many side effects. The purpose of this study was to determine the effects of intra-articular injection of Torin 1, which as a specific inhibitor of mTOR which can cause induction of autophagy, is similar to rapamycin, on articular cartilage degeneration in a rabbit osteoarthritis model and to investigate the mechanism of Torin 1’s effects on experimental OA. Methods Collagenase (type II) was injected twice into both knees of three-month-old rabbits to induce OA, combined with two intra–articular injections of Torin 1 (400 nM). Degeneration of articular cartilage was evaluated by histology using the Mankin scoring system at eight weeks after injection. Chondrocyte degeneration and autophagosomes were observed by transmission electron microscopy. Matrix metallopeptidase-13 (MMP-13) and vascular endothelial growth factor (VEGF) expression were analysed by quantitative RT-PCR (qPCR).Beclin-1 and light chain 3 (LC3) expression were examined by Western blotting. Results Intra-articular injection of Torin 1 significantly reduced degeneration of the articular cartilage after induction of OA. Autophagosomes andBeclin-1 and LC3 expression were increased in the chondrocytes from Torin 1-treated rabbits. Torin 1 treatment also reduced MMP-13 and VEGF expression at eight weeks after collagenase injection. Conclusion Our results demonstrate that intra-articular injection of Torin 1 reduces degeneration of articular cartilage in collagenase-induced OA, at least partially by autophagy activation, suggesting a novel therapeutic approach for preventing cartilage degeneration and treating OA. Cite this article: N-T. Cheng, A. Guo, Y-P. Cui. Intra-articular injection of Torin 1 reduces degeneration of articular cartilage in a

  11. Human Adipose-Derived Mesenchymal Progenitor Cells Engraft into Rabbit Articular Cartilage

    PubMed Central

    Wang, Wen; He, Na; Feng, Chenchen; Liu, Victor; Zhang, Luyi; Wang, Fei; He, Jiaping; Zhu, Tengfang; Wang, Shuyang; Qiao, Weiwei; Li, Suke; Zhou, Guangdong; Zhang, Li; Dai, Chengxiang; Cao, Wei

    2015-01-01

    Mesenchymal stem cells (MSCs) are known to have the potential for articular cartilage regeneration, and are suggested for the treatment of osteoarthritis (OA). Here, we investigated whether intra-articular injection of xenogeneic human adipose-derived mesenchymal progenitor cells (haMPCs) promoted articular cartilage repair in rabbit OA model and engrafted into rabbit articular cartilage. The haMPCs were cultured in vitro, and phenotypes and differentiation characteristics of cells were evaluated. OA was induced surgically by anterior cruciate ligament transection (ACLT) and medical meniscectomy of knee joints. At six weeks following surgery, hyaluronic acid (HA) or haMPCs was injected into the knee joints, the contralateral knee served as normal control. All animals were sacrificed at the 16th week post-surgery. Assessments were carried out by macroscopic examination, hematoxylin/eosin (HE) and Safranin-O/Fast green stainings and immunohistochemistry. The data showed that haMPC treatment promoted cartilage repair. Signals of human mitochondrial can be directly detected in haMPC treated cartilage. The haMPCs expressed human leukocyte antigen I (HLA-I) but not HLA-II-DR in vivo. These results suggest that intra-articular injection of haMPCs promotes regeneration of articular cartilage in rabbit OA model, and support the notion that MPCs are transplantable between HLA-incompatible individuals. PMID:26023716

  12. Genetic Inhibition of Fibroblast Growth Factor Receptor 1 in Knee Cartilage Attenuates the Degeneration of Articular Cartilage in Adult Mice

    PubMed Central

    Weng, Tujun; Yi, Lingxian; Huang, Junlan; Luo, Fengtao; Wen, Xuan; Du, Xiaolan; Chen, Qian; Deng, Chuxia; Chen, Di; Chen, Lin

    2013-01-01

    Objective Fibroblast growth factor (FGF) family members are involved in the regulation of articular cartilage homeostasis. The aim of this study was to investigate the function of FGF receptor 1 (FGFR-1) in the development of osteoarthritis (OA) and its underlying mechanisms. Methods FGFR-1 was deleted from the articular chondrocytes of adult mice in a cartilage-specific and tamoxifen-inducible manner. Two OA models (aging-associated spontaneous OA, and destabilization-induced OA), as well as an antigen-induced arthritis (AIA) model, were established and tested in Fgfr1-deficient and wild-type (WT) mice. Alterations in cartilage structure and the loss of proteoglycan were assessed in the knee joints of mice of either genotype, using these 3 arthritis models. Primary chondrocytes were isolated and the expression of key regulatory molecules was assessed quantitatively. In addition, the effect of an FGFR-1 inhibitor on human articular chondrocytes was examined. Results The gross morphologic features of Fgfr1-deficient mice were comparable with those of WT mice at both the postnatal and adult stages. The articular cartilage of 12-month-old Fgfr1-deficient mice displayed greater aggrecan staining compared to 12-month-old WT mice. Fgfr1 deficiency conferred resistance to the proteoglycan loss induced by AIA and attenuated the development of cartilage destruction after surgically induced destabilization of the knee joint. The chondroprotective effect of FGFR-1 inhibition was largely associated with decreased expression of matrix metalloproteinase 13 (MMP-13) and up-regulation of FGFR-3 in mouse and human articular chondrocytes. Conclusion Disruption of FGFR-1 in adult mouse articular chondrocytes inhibits the progression of cartilage degeneration. Down-regulation of MMP-13 expression and up-regulation of FGFR-3 levels may contribute to the phenotypic changes observed in Fgfr1-deficient mice. PMID:22833219

  13. Comparison of nonlinear mechanical properties of bovine articular cartilage and meniscus.

    PubMed

    Danso, E K; Honkanen, J T J; Saarakkala, S; Korhonen, R K

    2014-01-01

    Nonlinear, linear and failure properties of articular cartilage and meniscus in opposing contact surfaces are poorly known in tension. Relationships between the tensile properties of articular cartilage and meniscus in contact with each other within knee joints are also not known. In the present study, rectangular samples were prepared from the superficial lateral femoral condyle cartilage and lateral meniscus of bovine knee joints. Tensile tests were carried out with a loading rate of 5mm/min until the tissue rupture. Nonlinear properties of the toe region, linear properties in larger strains, and failure properties of both tissues were analysed. The strain-dependent tensile modulus of the toe region, Young's modulus of the linear region, ultimate tensile stress and toughness were on average 98.2, 8.3, 4.0 and 1.9 times greater (p<0.05) for meniscus than for articular cartilage. In contrast, the toe region strain, yield strain and failure strain were on average 9.4, 3.1 and 2.3 times greater (p<0.05) for cartilage than for meniscus. There was a significant negative correlation between the strain-dependent tensile moduli of meniscus and articular cartilage samples within the same joints (r=-0.690, p=0.014). In conclusion, the meniscus possesses higher nonlinear and linear elastic stiffness and energy absorption capability before rupture than contacting articular cartilage, while cartilage has longer nonlinear region and can withstand greater strains before failure. These findings point out different load carrying demands that both articular cartilage and meniscus have to fulfil during normal physiological loading activities of knee joints. PMID:24182695

  14. MRI-based inverse finite element approach for the mechanical assessment of patellar articular cartilage from static compression test.

    PubMed

    Knecht, Sven; Luechinger, Roger; Boesiger, Peter; Stüssi, Edgar

    2008-12-01

    The mechanical property of articular cartilage determines to a great extent the functionality of diarthrodial joints. Consequently, the early detection of mechanical and, thus, functional changes of cartilage is crucial for preventive measures to maintain the mobility and the quality of life of individuals. An alternative to conventional mechanical testing is the inverse finite element approach, enabling non-destructive testing of the tissue. We evaluated a method for the assessment of the equilibrium material properties of the patellar cartilage based on magnetic resonance imaging during patellofemoral compression. We performed ex vivo testing of two equine patellas with healthy cartilage, one with superficial defects, and one with synthetically degenerated cartilage to simulate a pre-osteoarthritic stage. Static compression with 400 N for 2 h resulted in morphological changes comparable to physiological in vivo deformations in humans. We observed a decrease of the equilibrium Young's modulus of the degenerated cartilage by -59%, which was in the range of the results from indentation (-74%) and confined compression tests (-58%). With the reported accuracy of magnetic resonance imaging and its reproducibility, the results indicate the potential to measure differences in Young's modulus with regard to cartilage degeneration and consequently to distinguish between healthy and pre-osteoarthritic cartilage. PMID:19037871

  15. Physiological assessment of in vivo human knee articular cartilage using sodium MR imaging at 1.5 T.

    PubMed

    Hani, Ahmad Fadzil Mohd; Kumar, Dileep; Malik, Aamir Saeed; Razak, Ruslan

    2013-09-01

    Osteoarthritis is a common joint disorder that is most prevalent in the knee joint. Knee osteoarthritis (OA) can be characterized by the gradual loss of articular cartilage (AC). Formation of lesion, fissures and cracks on the cartilage surface has been associated with degenerative AC and can be measured by morphological assessment. In addition, loss of proteoglycan from extracellular matrix of the AC can be measured at early stage of cartilage degradation by physiological assessment. In this case, a biochemical phenomenon of cartilage is used to assess the changes at early degeneration of AC. In this paper, a method to measure local sodium concentration in AC due to proteoglycan has been investigated. A clinical 1.5-T magnetic resonance imaging (MRI) with multinuclear spectroscopic facility is used to acquire sodium images and quantify local sodium content of AC. An optimised 3D gradient-echo sequence with low echo time has been used for MR scan. The estimated sodium concentration in AC region from four different data sets is found to be ~225±19mmol/l, which matches the values that has been reported for the normal AC. This study shows that sodium images acquired at clinical 1.5-T MRI system can generate an adequate quantitative data that enable the estimation of sodium concentration in AC. We conclude that this method is potentially suitable for non-invasive physiological (sodium content) measurement of articular cartilage. PMID:23731535

  16. 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. PMID:26294356

  17. Role of uppermost superficial surface layer of articular cartilage in the lubrication mechanism of joints

    PubMed Central

    KUMAR, P.; OKA, M.; TOGUCHIDA, J.; KOBAYASHI, M.; UCHIDA, E.; NAKAMURA, T.; TANAKA, K.

    2001-01-01

    The uppermost superficial surface layer of articular cartilage, the ‘lamina splendens’ which provides a very low friction lubrication surface in articular joints, was investigated using atomic force microscopy (AFM). Complementary specimens were also observed under SEM at −10 °C without dehydration or sputter ion coating. Fresh adult pig osteochondral specimens were prepared from the patellas of pig knee joints and digested with the enzymes, hyaluronidase, chondroitinase ABC and alkaline protease. Friction coefficients between a pyrex glass plate and the osteochondral specimens digested by enzymes as well as natural (undigested) specimens were measured, using a thrust collar apparatus. Normal saline, hyaluronic acid (HA) and a mixture of albumin, globulin, HA (AGH) were used as lubrication media. The surface irregularities usually observed in SEM studies were not apparent under AFM. The articular cartilage surface was resistant to hyaluronidase and also to chondroitinase ABC, but a fibrous structure was exhibited in alkaline protease enzymes-digested specimens. AFM analysis revealed that the thickness of the uppermost superficial surface layer of articular cartilage was between 800 nm and 2 μm in adult pig articular cartilage. The coefficient of friction (c.f.) was significantly higher in chondroitinase ABC and alkaline protease enzymes digested specimens. Generally, in normal saline lubrication medium, c.f. was higher in comparison to HA and AGH lubrication media. The role of the uppermost, superficial surface layer of articular cartilage in the lubrication mechanism of joints is discussed. PMID:11554503

  18. Role of uppermost superficial surface layer of articular cartilage in the lubrication mechanism of joints.

    PubMed

    Kumar, P; Oka, M; Toguchida, J; Kobayashi, M; Uchida, E; Nakamura, T; Tanaka, K

    2001-09-01

    The uppermost superficial surface layer of articular cartilage, the 'lamina splendens' which provides a very low friction lubrication surface in articular joints, was investigated using atomic force microscopy (AFM). Complementary specimens were also observed under SEM at -10 degrees C without dehydration or sputter ion coating. Fresh adult pig osteochondral specimens were prepared from the patellas of pig knee joints and digested with the enzymes, hyaluronidase, chondroitinase ABC and alkaline protease. Friction coefficients between a pyrex glass plate and the osteochondral specimens digested by enzymes as well as natural (undigested) specimens were measured, using a thrust collar apparatus. Normal saline, hyaluronic acid (HA) and a mixture of albumin, globulin, HA (AGH) were used as lubrication media. The surface irregularities usually observed in SEM studies were not apparent under AFM. The articular cartilage surface was resistant to hyaluronidase and also to chondroitinase ABC, but a fibrous structure was exhibited in alkaline protease enzymes-digested specimens. AFM analysis revealed that the thickness of the uppermost superficial surface layer of articular cartilage was between 800 nm and 2 microm in adult pig articular cartilage. The coefficient of friction (c.f.) was significantly higher in chondroitinase ABC and alkaline protease enzymes digested specimens. Generally, in normal saline lubrication medium, c.f. was higher in comparison to HA and AGH lubrication media. The role of the uppermost, superficial surface layer of articular cartilage in the lubrication mechanism of joints is discussed. PMID:11554503

  19. T1 assessment of hip joint cartilage following intra-articular gadolinium injection: a pilot study.

    PubMed

    Bittersohl, Bernd; Hosalkar, Harish S; Kim, Young-Jo; Werlen, Stefan; Trattnig, Siegfried; Siebenrock, Klaus A; Mamisch, Tallal C

    2010-10-01

    This pilot study defines the feasibility of cartilage assessment in symptomatic femoroacetabular impingement patients using intra-articular delayed gadolinium-enhanced MRI of cartilage (ia-dGEMRIC). Nine patients were scanned preliminary to study the contrast infiltration process into hip joint cartilage. Twenty-seven patients with symptomatic femoroacetabular impingement were subsequently scanned with intra-articular delayed gadolinium-enhanced MRI of cartilage. These T(1) findings were correlated to morphological findings. Zonal variations were studied. This pilot study demonstrates a significant difference between the pre- and postcontrast T(1) values (P < 0.001) remaining constant for 45 min. We noted higher mean T(1) values in morphologically normal-appearing cartilage than in damaged cartilage, which was statistically significant for all zones except the anterior-superior zone. Intraobserver (0.972) and interobserver correlation coefficients (0.933) were statistically significant. This study outlines the feasibility of intra-articular delayed gadolinium-enhanced MRI of cartilage for assessment of cartilage changes in patients with femoroacetabular impingement. It can also define the topographic extent and differing severities of cartilage damage. PMID:20872764

  20. Treatment of Focal Articular Cartilage Defects in the Knee

    PubMed Central

    Magnussen, Robert A.; Dunn, Warren R.; Carey, James L.

    2008-01-01

    We asked whether autologous chondrocyte implantation or osteochondral autograft transfer yields better clinical outcomes compared with one another or with traditional abrasive techniques for treatment of isolated articular cartilage defects and whether lesion size influences this clinical outcome. We performed a literature search and identified five randomized, controlled trials and one prospective comparative trial evaluating these treatment techniques in 421 patients. The operative procedures included autologous chondrocyte implantation, osteochondral autograft transfer, matrix-induced autologous chondrocyte implantation, and microfracture. Minimum followup was 1 year (mean, 1.7 years; range, 1–3 years). All studies documented greater than 95% followup for clinical outcome measures. No technique consistently had superior results compared with the others. Outcomes for microfracture tended to be worse in larger lesions. All studies reported improvement in clinical outcome measures in all treatment groups when compared with preoperative assessment; however, no control (nonoperative) groups were used in any of the studies. A large prospective trial investigating these techniques with the addition of a control group would be the best way to definitively address the clinical questions. Level of Evidence: Level II, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence. PMID:18196358

  1. Localization of hyaluronic acid in human articular cartilage.

    PubMed

    Asari, A; Miyauchi, S; Kuriyama, S; Machida, A; Kohno, K; Uchiyama, Y

    1994-04-01

    To demonstrate localization of hyaluronic acid (HA) in articular cartilage of the human femur, biotinylated HA-binding region, which specifically binds HA molecules, was applied to the tissue. In sections fixed by 2% paraformaldehyde-2% glutaraldehyde, HA staining was detected in lamina splendens and chondrocytes in the middle zone. By pretreatment with trypsin, intense HA staining appeared in the extracellular matrix of the deep zone and weak staining in the superficial and middle zones. Moreover, pre-treatment with chondroitinase ABC (CHase ABC) intensely enhanced the stainability for HA in the superficial and middle zones and weakly in the deeper zone. Combined pre-treatment of trypsin with CHase ABC abolished intra- and extracellular staining for HA in all zones. By microbiochemical study, the concentrations of HA and dermatan sulfate were high in the middle zone, whereas those of chondroitin sulfate and keratan sulfate were high in the deep zone. These results suggest that HA is abundantly synthesized in and secreted from the chondrocytes, particularly in the middle zone, whereas it is largely masked by proteoglycan constituents in the extracellular matrix. PMID:8126377

  2. 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).

  3. Age related changes and osteochondrosis in swine articular and epiphyseal cartilage: light ane electron microscopy.

    PubMed

    Bhatnagar, R; Christian, R G; Nakano, T; Aherne, F X; Thompson, J R

    1981-04-01

    Age related changes and osteochondrosis in swine were studied using light microscopy and electron microscopy in articular cartilage and light microscopy and epiphyseal cartilage of swine from three days to 30 weeks of age. Thickness, cellularity and vascularity of both the epiphyseal and articular cartilage, decreased as the swine aged. Osteochondrotic changes included formation of "plugs" of cartilage indicating localized failure of ossification and separation and space formation in epiphyseal cartilage. Eosinophilic streaks and space formation in epiphyseal cartilage was observed in relation to epiphyseal separation. Electron microscopy showed a continuous fibrillar layer on the surface of the cartilage corresponding to the lamina splendens of light microscopy. This layer increased in the thickness and showed accumulation of amorphous material between the fibrils with aging. In the matrix, the orientation and distribution of the collagen fibers changed with growth and thicker fibers with clear sub banding were more common in older age groups. Also, necrotic cells, glycogen containing bodies and cellular debris were noticed in the matrix of normal cartilage in old animals. Chondrocytes in the younger cartilage showed accumulation of organelles responsible for protein synthesis; while Golgi bodies, vesicles, lysosomes, well developed foot processes and other inclusions were noticed in older cartilage. Cartilage erosions had a clumped and disrupted lamina splendens on the surface and electron lucent patches in the ground substances of the matrix and chondrocyte cytoplasm. PMID:7260732

  4. Quantitative characterization of articular cartilage using Mueller matrix imaging and multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Ellingsen, Pa˚L. Gunnar; Lilledahl, Magnus Borstad; Aas, Lars Martin Sandvik; Davies, Catharina De Lange; Kildemo, Morten

    2011-11-01

    The collagen meshwork in articular cartilage of chicken knee is characterized using Mueller matrix imaging and multiphoton microscopy. Direction and degree of dispersion of the collagen fibers in the superficial layer are found using a Fourier transform image-analysis technique of the second-harmonic generated image. Mueller matrix images are used to acquire structural data from the intermediate layer of articular cartilage where the collagen fibers are too small to be resolved by optical microscopy, providing a powerful multimodal measurement technique. Furthermore, we show that Mueller matrix imaging provides more information about the tissue compared to standard polarization microscopy. The combination of these techniques can find use in improved diagnosis of diseases in articular cartilage, improved histopathology, and additional information for accurate biomechanical modeling of cartilage.

  5. Demonstration of fibronectin in human articular cartilage by an indirect immunoperoxidase technique.

    PubMed

    Clemmensen, I; Hølund, B; Johansen, N; Andersen, R B

    1982-01-01

    Fresh frozen tissue sections of human articular cartilage was treated without and with human testicular hyaluronidase (2 x 10(6) units/l) for 60 min at 37 degrees C and stained by the indirect immunoperoxidase technique with rabbit antihuman fibronectin. The rabbit antihuman fibronectin was purified by affinity chromatography on human fibronectin-Sepharose. Fibronectin was only found on the acellular surface of the articular cartilage in tissue sections not treated with hyaluronidase. In this surface layer, probably identical to "lamina splendens", the arrangement of fibronectin was as a membrane. No collagen was seen in this area by van Gieson staining. No staining for fibronectin was found in the cartilage matrix or in the chondrocytes. Treatment of the cartilage tissue with hyaluronidase resulted in visualization of high amount of fibronectin in the cartilage matrix, with the highest intensity around the chondrocytes. The staining of the acellular surface layer of the articular cartilage was identical with the results obtained without hyaluronidase treatment. These results indicate that articular cartilage is rich in fibronectin probably in complex with hyaluronic acid, and that the chondrocytes produce fibronectin in situ. It also demonstrates the steric hindrance of hyaluronic acid aggregates in diffusion of the antibody and the value of hyaluronidase treatment of tissue before demonstration of fibronectin. PMID:6757202

  6. The protective effect of meniscus allograft transplantation on articular cartilage: a systematic review of animal studies.

    PubMed

    Rongen, J J; Hannink, G; van Tienen, T G; van Luijk, J; Hooijmans, C R

    2015-08-01

    Despite widespread reporting on clinical results, the effect of meniscus allograft transplantation on the development of osteoarthritis is still unclear. The aim of this study was to systematically review all studies on the effect of meniscus allograft transplantation on articular cartilage in animals. Pubmed and Embase were searched for original articles concerning the effect of meniscus allograft transplantation on articular cartilage compared with both its positive (meniscectomy) and negative (either sham or non-operated) control in healthy animals. Outcome measures related to assessment of damage to articular cartilage were divided in five principal outcome categories. Standardized mean differences (SMD) were calculated and pooled to obtain an overall SMD and 95% confidence interval. 17 articles were identified, representing 14 original animal cohorts with an average timing of data collection of 24 weeks [range 4 weeks; 30 months]. Compared to a negative control, meniscus allograft transplantation caused gross macroscopic (1.45 [0.95; 1.95]), histological (3.43 [2.25; 4.61]) damage to articular cartilage, and osteoarthritic changes on radiographs (3.12 [1.42; 4.82]). Moreover, results on histomorphometrics and cartilage biomechanics are supportive of this detrimental effect on cartilage. On the other hand, meniscus allograft transplantation caused significantly less gross macroscopic (-1.19 [-1.84; -0.54]) and histological (-1.70 [-2.67; -0.74]) damage to articular cartilage when compared to meniscectomy. However, there was no difference in osteoarthritic changes on plain radiographs (0.04 [-0.48; 0.57]), and results on histomorphometrics and biomechanics did neither show a difference in effect between meniscus allograft transplantation and meniscectomy. In conclusion, although meniscus allograft transplantation does not protect articular cartilage from damage, it reduces the extent of it when compared with meniscectomy. PMID:25960117

  7. The Effects of Anterior Cruciate Ligament Deficiency on the Meniscus and Articular Cartilage

    PubMed Central

    Arner, Justin W.; Irvine, James N.; Zheng, Liying; Gale, Tom; Thorhauer, Eric; Hankins, Margaret; Abebe, Ermias; Tashman, Scott; Zhang, Xudong; Harner, Christopher D.

    2016-01-01

    Background: Anterior cruciate ligament (ACL) injury increases the risk of meniscus and articular cartilage damage, but the causes are not well understood. Previous in vitro studies were static, required extensive knee dissection, and likely altered meniscal and cartilage contact due to the insertion of pressure sensing devices. Hypothesis: ACL deficiency will lead to increased translation of the lateral meniscus and increased deformation of the medial meniscus as well as alter cartilage contact location, strain, and area. Study Design: Descriptive laboratory study. Methods: With minimally invasive techniques, six 1.0-mm tantalum beads were implanted into the medial and lateral menisci of 6 fresh-frozen cadaveric knees. Dynamic stereo x-rays (DSXs) were obtained during dynamic knee flexion (from 15° to 60°, simulating a standing squat) with a 46-kg load in intact and ACL-deficient states. Knee kinematics, meniscal movement and deformation, and cartilage contact were compared by novel imaging coregistration. Results: During dynamic knee flexion from 15° to 60°, the tibia translated 2.6 mm (P = .05) more anteriorly, with 2.3° more internal rotation (P = .04) with ACL deficiency. The medial and lateral menisci, respectively, translated posteriorly an additional 0.7 mm (P = .05) and 1.0 mm (P = .03). Medial and lateral compartment cartilage contact location moved posteriorly (2.0 mm [P = .05] and 2.0 mm [P = .04], respectively). Conclusion: The lateral meniscus showed greater translation with ACL deficiency compared with the medial meniscus, which may explain the greater incidences of acute lateral meniscus tears and chronic medial meniscus tears. Furthermore, cartilage contact location moved further posteriorly than that of the meniscus in both compartments, possibly imparting more meniscal stresses that may lead to early degeneration. This new, minimally invasive, dynamic in vitro model allows the study of meniscus function and cartilage contact and can be

  8. A microanalytical study of the surfaces of normal, delipidized, and artificially "resurfaced" articular cartilage.

    PubMed

    Yusuf, Kehinde Quasim; Motta, Nunzio; Pawlak, Zenon; Oloyede, Adekunle

    2012-01-01

    The surface amorphous layer of articular cartilage is of primary importance to its load-bearing and lubrication function. This lipid-filled layer is degraded/disrupted or eliminated when cartilage degenerates due to diseases. This article examines further the characteristic of this surface overlay using a combination of microscopy and imaging methods to evaluate the hypothesis that the surface of articular cartilage can be repaired by exposing degraded cartilage to aqueous synthetic lipid mixtures. The preliminary results demonstrate that it is possible to create a new surface layer of phospholipids on the surface of cartilage following artificial lipid removal, but such a layer does not possess enough mechanical strength for physiological function when created with either unsaturated palmitoyl-oleoyl-phosphatidylcholine or saturated dipalmitoyl-phosphatidylcholine component of joint lipid composition alone. We conclude that this may be due to low structural cohesivity, inadequate time of exposure, and the mix/content of lipid in the incubation environment. PMID:22141914

  9. Strategic Design and Fabrication of Engineered Scaffolds for Articular Cartilage Repair

    PubMed Central

    Izadifar, Zohreh; Chen, Xiongbiao; Kulyk, William

    2012-01-01

    Damage to articular cartilage can eventually lead to osteoarthritis (OA), a debilitating, degenerative joint disease that affects millions of people around the world. The limited natural healing ability of cartilage and the limitations of currently available therapies make treatment of cartilage defects a challenging clinical issue. Hopes have been raised for the repair of articular cartilage with the help of supportive structures, called scaffolds, created through tissue engineering (TE). Over the past two decades, different designs and fabrication techniques have been investigated for developing TE scaffolds suitable for the construction of transplantable artificial cartilage tissue substitutes. Advances in fabrication technologies now enable the strategic design of scaffolds with complex, biomimetic structures and properties. In particular, scaffolds with hybrid and/or biomimetic zonal designs have recently been developed for cartilage tissue engineering applications. This paper reviews critical aspects of the design of engineered scaffolds for articular cartilage repair as well as the available advanced fabrication techniques. In addition, recent studies on the design of hybrid and zonal scaffolds for use in cartilage tissue repair are highlighted. PMID:24955748

  10. Optical Determination of Anisotropic Material Properties of Bovine Articular Cartilage in Compression

    PubMed Central

    Wang, Christopher C-B.; Chahine, Nadeen O.; Hung, Clark T.; Ateshian, Gerard A.

    2010-01-01

    The precise nature of the material symmetry of articular cartilage in compression remains to be elucidated. The primary objective of this study was to determine the equilibrium compressive Young’s moduli and Poisson’s ratios of bovine cartilage along multiple directions (parallel and perpendicular to the split line direction, and normal to the articular surface) by loading small cubic specimens (0.9×0.9×0.8 mm, n=15) in unconfined compression, with the expectation that the material symmetry of cartilage could be determined more accurately with the help of a more complete set of material properties. The second objective was to investigate how the tension-compression nonlinearity of cartilage might alter the interpretation of material symmetry. Optimized digital image correlation was used to accurately determine the resultant strain fields within the specimens under loading. Experimental results demonstrated that neither the Young’s moduli nor the Poisson’s ratios exhibit the same values when measured along the three loading directions. The main findings of this study are that the framework of linear orthotropic elasticity (as well as higher symmetries of linear elasticity) is not suitable to describe the equilibrium response of articular cartilage nor characterize its material symmetry; a framework which accounts for the distinctly different responses of cartilage in tension and compression is more suitable for describing the equilibrium response of cartilage; within this framework, cartilage exhibits no lower than orthotropic symmetry. PMID:12594982

  11. The study on the mechanical characteristics of articular cartilage in simulated microgravity

    NASA Astrophysics Data System (ADS)

    Niu, Hai-Jun; Wang, Qing; Wang, Yue-Xiang; Li, Ang; Sun, Lian-Wen; Yan, Yan; Fan, Fan; Li, De-Yu; Fan, Yu-Bo

    2012-10-01

    The microgravity environment of a long-term space flight may induce acute changes in an astronaut's musculo-skeletal systems. This study explores the effects of simulated microgravity on the mechanical characteristics of articular cartilage. Six rats underwent tail suspension for 14 days and six additional rats were kept under normal earth gravity as controls. Swelling strains were measured using high-frequency ultrasound in all cartilage samples subject to osmotic loading. Site-specific swelling strain data were used in a triphasic theoretical model of cartilage swelling to determine the uniaxial modulus of the cartilage solid matrix. No severe surface irregularities were found in the cartilage samples obtained from the control or tail-suspended groups. For the tail-suspended group, the thickness of the cartilage at a specified site, as determined by ultrasound echo, showed a minor decrease. The uniaxial modulus of articular cartilage at the specified site decreased significantly, from (6.31 ± 3.37)MPa to (5.05 ± 2.98)MPa ( p < 0.05). The histology-stained image of a cartilage sample also showed a reduced number of chondrocytes and decreased degree of matrix staining. These results demonstrated that the 14 d simulated microgravity induced significant effects on the mechanical characteristics of articular cartilage. This study is the first attempt to explore the effects of simulated microgravity on the mechanical characteristics of articular cartilage using an osmotic loading method and a triphasic model. The conclusions may provide reference information for manned space flights and a better understanding of the effects of microgravity on the skeletal system.

  12. Role of computer aided detection (CAD) integration: case study with meniscal and articular cartilage CAD applications

    NASA Astrophysics Data System (ADS)

    Safdar, Nabile; Ramakrishna, Bharath; Saiprasad, Ganesh; Siddiqui, Khan; Siegel, Eliot

    2008-03-01

    Knee-related injuries involving the meniscal or articular cartilage are common and require accurate diagnosis and surgical intervention when appropriate. With proper techniques and experience, confidence in detection of meniscal tears and articular cartilage abnormalities can be quite high. However, for radiologists without musculoskeletal training, diagnosis of such abnormalities can be challenging. In this paper, the potential of improving diagnosis through integration of computer-aided detection (CAD) algorithms for automatic detection of meniscal tears and articular cartilage injuries of the knees is studied. An integrated approach in which the results of algorithms evaluating either meniscal tears or articular cartilage injuries provide feedback to each other is believed to improve the diagnostic accuracy of the individual CAD algorithms due to the known association between abnormalities in these distinct anatomic structures. The correlation between meniscal tears and articular cartilage injuries is exploited to improve the final diagnostic results of the individual algorithms. Preliminary results from the integrated application are encouraging and more comprehensive tests are being planned.

  13. Characterization of Chondrocyte Scaffold Carriers for Cell-based Gene Therapy in Articular Cartilage Repair

    PubMed Central

    Shui, Wei; Yin, Liangjun; Luo, Jeffrey; Li, Ruidong; Zhang, Wenwen; Zhang, Jiye; Huang, Wei; Hu, Ning; Liang, Xi; Deng, Zhong-Liang; Hu, Zhenming; Shi, Lewis; Luu, Hue H.; Haydon, Rex C.; He, Tong-Chuan; Ho, Sherwin

    2014-01-01

    Articular cartilage lesions in the knee are common injuries. Chondrocyte transplant represents a promising therapeutic modality for articular cartilage injuries. Here, we characterize the viability and transgene expression of articular chondrocytes cultured in 3-D scaffolds provided by four types of carriers. Articular chondrocytes are isolated from rabbit knees and cultured in four types of scaffolds: type I collagen sponge, fibrin glue, hyaluronan, and Open-cell PolyLactic Acid (OPLA). The cultured cells are transduced with adenovirus expressing green fluorescence protein (AdGFP) and luciferase (AdGL3-Luc). The viability and gene expression in the chondrocytes are determined with fluorescence microscopy and luciferase assay. Cartilage matrix production is assessed by Alcian blue staining. Rabbit articular chondrocytes are effectively infected by AdGFP and exhibited sustained GFP expression. All tested scaffolds support the survival and gene expression of the infected chondrocytes. However, the highest transgene expression is observed in the OPLA carrier. At four weeks, Alcian blue-positive matrix materials are readily detected in OPLA cultures. Thus, our results indicate that, while all tested carriers can support the survival of chondrocytes, OPLA supports the highest transgene expression and is the most conductive scaffold for matrix production, suggesting that OPLA may be a suitable scaffold for cell-based gene therapy of articular cartilage repairs. PMID:23629940

  14. Biological Effects of the Plant-derived Polyphenol Resveratrol in Human Articular Cartilage and Chondrosarcoma Cells

    PubMed Central

    Im, Hee-Jeong; Li, Xin; Chen, Di; Yan, Dongyao; Kim, Jaesung; Ellman, Michael B; Stein, Gary S.; Cole, Brian; Ranjan, KC; Cs-Szabo, Gabriella; van Wijnen, Andre J

    2012-01-01

    The natural phytoestrogen resveratrol (RSV) may have therapeutic potential for arthritic conditions. RSV is chondroprotective for articular cartilage in rabbit models for arthritis, but its biological effects on human articular cartilage and chondrosarcoma cells are unknown. Effects of RSV on human articular cartilage homeostasis were studied by assessing production of matrix-degrading enzymes (MMP-13, ADAMTS-4, and ADAMTS-5), as well as proteoglycan production and synthesis. The counteractions of RSV against catabolic factors (e.g., FGF-2 or IL-1β) were examined by in vitro and ex vivo using monolayer, three-dimensional alginate beads and cartilage explants cultures, respectively. RSV improves cell viability of articular chondrocytes and effectively antagonizes cartilage-degrading protease production that was initiated by catabolic and/or anti-anabolic cytokines in human articular chondrocytes. RSV significantly also enhances BMP7-promoted proteoglycan synthesis as assessed by 35S-sulfate incorporation. Protein-DNA interaction arrays suggest that RSV inhibits the activation of transcription factors involved in inflammation and cartilage catabolic signaling pathways, including direct downstream regulators of MAPK (e.g., AP-1, PEA3) and NFκB. RSV selectively compromises survival of human chondrosarcoma cells, but not primary articular chondrocytes, revealing cell-specific activity of RSV on non-tumorigenic versus tumor-derived cells. We propose that RSV exerts its chondroprotective functions, in part, by deactivating p53-induced apoptosis in human primary chondrocytes, but not human chondrosarcoma. Our findings suggest that RSV has potential as a unique biologic treatment for both prevention and treatment of cartilage degenerative diseases. PMID:22252971

  15. An Articular Cartilage Repair Model in Common C57Bl/6 Mice

    PubMed Central

    Matsuoka, Masatake; Sasazawa, Fumio; Momma, Daisuke; Baba, Rikiya; Hontani, Kazutoshi; Iwasaki, Norimasa

    2015-01-01

    To analyze the genetic and biomolecular mechanisms underlying cartilage repair, an optimized mouse model of osteochondral repair is required. Although several models of articular cartilage injury in mice have recently been established, the articular surface in adult C57Bl/6 mice heals poorly. Since C57Bl/6 mice are the most popular strain of genetically manipulated mice, an articular cartilage repair model using C57Bl/6 mice would be helpful for analysis of the mechanisms of cartilage repair. The purpose of this study was to establish a cartilage repair model in C57Bl/6 mice using immature animals. To achieve this goal, full-thickness injuries were generated in 3-week-old (young), 4-week-old (juvenile), and 8-week-old (adult) C57Bl/6 mice. To investigate the reproducibility and consistency of full-thickness injuries, mice were sacrificed immediately after operation, and cartilage thickness at the patellar groove, depth of the cartilage injury, cross-sectional width, and cross-sectional area were compared among the three age groups. The depth of cartilage injury/cartilage thickness ratio (%depth) and the coefficient of variation (CV) for each parameter were also calculated. At 8 weeks postoperatively, articular cartilage repair was assessed using a histological scoring system. With respect to the reproducibility and consistency of full-thickness injuries, cartilage thickness, depth of cartilage injury, and cross-sectional area were significantly larger in young and juvenile mice than in adult mice, whereas cross-sectional width and %depth were almost equal among the three age groups. CVs of %depths were less than 10% in all groups. With respect to articular cartilage repair, young and juvenile mice showed superior results. In conclusion, we established a novel cartilage repair model in C57Bl/6 mice. This model will be valuable in achieving mechanistic insights into the healing process of the joint surface, as it will facilitate the use of genetically modified mice

  16. FRICTIONAL RESPONSE OF BOVINE ARTICULAR CARTILAGE UNDER CREEP LOADING FOLLOWING PROTEOGLYCAN DIGESTION WITH CHONDROITINASE ABC

    PubMed Central

    Basalo, Ines M.; Chen, Faye Hui; Hung, Clark T.; Ateshian, Gerard A.

    2010-01-01

    Summary The specific aim of this study was to investigate the effect of chondroitinase ABC treatment on the frictional response of bovine articular cartilage against glass, under creep loading. The hypothesis is that chondroitinase ABC treatment increases the friction coefficient of bovine articular cartilage under creep. Articular cartilage samples (n=12) harvested from two bovine knee joints (1–3 months-old) were divided into a control group (intact specimens) and a treated group (chondroitinase ABC digestion), and tested in unconfined compression with simultaneous continuous sliding (±4 mm at 1 mm/s) under a constant applied stress of 0.5 MPa, for 2,500 s. The time-dependent response of the friction coefficient was measured. With increasing duration of loading, treated samples exhibited a significantly higher friction coefficient than control samples as assessed by the equilibrium value (treated: μeq = 0.19 ± 0.02; control: μeq = 0.12 ± 0.03; p=0.002), though the coefficient achieved immediately upon loading did not increase significantly (treated: μmin = 0.0053 ± 0.0025; control: μmin = 0.037 ± 0.0013; p=0.19). Our results demonstrate that removal of the cartilage glycosaminoglycans using chondroitinase ABC significantly increases the overall time-dependent friction coefficient of articular cartilage. These findings strengthen the motivation for developing chondroprotective strategies by increasing cartilage chondroitin sulfate content in osteoarthritic joints. PMID:16532626

  17. Noncontact evaluation of articular cartilage degeneration using a novel ultrasound water jet indentation system.

    PubMed

    Lu, M-H; Zheng, Y P; Huang, Q-H; Ling, C; Wang, Q; Bridal, L; Qin, L; Mak, A

    2009-01-01

    We previously reported a noncontact ultrasound water jet indentation system for measuring and mapping tissue mechanical properties. The key idea was to utilize a water jet as an indenter as well as the coupling medium for high-frequency ultrasound. In this paper, the system was employed to assess articular cartilage degeneration, using stiffness ratio as an indicator of the mechanical properties of samples. Both the mechanical and acoustical properties of intact and degenerated bovine patellar articular cartilage (n = 8) were obtained in situ. It was found that the stiffness ratio was reduced by 44 +/- 17% after the articular cartilage was treated by 0.25% trypsin at 37 degrees C for 4 h while no significant difference in thickness was observed between the intact and degenerated samples. A significant decrease of 36 +/- 20% in the peak-to-peak amplitude of ultrasound echoes reflected from the cartilage surface was also found for the cartilage samples treated by trypsin. The results also showed that the stiffness obtained with the new method highly correlated with that measured using a standard mechanical testing protocol. A good reproducibility of the measurements was demonstrated. The present results showed that the ultrasound water jet indentation system may provide a potential tool for the non-destructive evaluation of articular cartilage degeneration by simultaneously obtaining mechanical properties, acoustical properties, and thickness data. PMID:19011965

  18. Adult human neural crest-derived cells for articular cartilage repair.

    PubMed

    Pelttari, Karoliina; Pippenger, Benjamin; Mumme, Marcus; Feliciano, Sandra; Scotti, Celeste; Mainil-Varlet, Pierre; Procino, Alfredo; von Rechenberg, Brigitte; Schwamborn, Thomas; Jakob, Marcel; Cillo, Clemente; Barbero, Andrea; Martin, Ivan

    2014-08-27

    In embryonic models and stem cell systems, mesenchymal cells derived from the neuroectoderm can be distinguished from mesoderm-derived cells by their Hox-negative profile--a phenotype associated with enhanced capacity of tissue regeneration. We investigated whether developmental origin and Hox negativity correlated with self-renewal and environmental plasticity also in differentiated cells from adults. Using hyaline cartilage as a model, we showed that adult human neuroectoderm-derived nasal chondrocytes (NCs) can be constitutively distinguished from mesoderm-derived articular chondrocytes (ACs) by lack of expression of specific HOX genes, including HOXC4 and HOXD8. In contrast to ACs, serially cloned NCs could be continuously reverted from differentiated to dedifferentiated states, conserving the ability to form cartilage tissue in vitro and in vivo. NCs could also be reprogrammed to stably express Hox genes typical of ACs upon implantation into goat articular cartilage defects, directly contributing to cartilage repair. Our findings identify previously unrecognized regenerative properties of HOX-negative differentiated neuroectoderm cells in adults, implying a role for NCs in the unmet clinical challenge of articular cartilage repair. An ongoing phase 1 clinical trial preliminarily indicated the safety and feasibility of autologous NC-based engineered tissues for the treatment of traumatic articular cartilage lesions. PMID:25163479

  19. Immunohistochemical demonstration of fibronectin in the most superficial layer of normal rabbit articular cartilage.

    PubMed Central

    Nishida, K; Inoue, H; Murakami, T

    1995-01-01

    OBJECTIVE--To locate fibronectin ultrastructurally in the most superficial layer of normal articular cartilage of rabbits, in order to clarify its role in joint physiology. METHODS--Articular cartilage was obtained from the femoral condyle of seven normal adult rabbits and prepared by a method that included tannic acid fixation. Polyclonal antibodies against rabbit fibronectin were used in an immunohistochemical electron microscopic study, without any enzymic digestion but with a pre-embedding method for the transmission electron microscopy. RESULTS--The cartilage surface was successfully preserved by tannic acid fixation. The most superficial layer in electron photomicrographs was approximately 200-300 nm thick, cell free, and appeared to have two parallel components: the more superficial lamina and the deeper lamina. Gold labelled fibronectin lined this layer in immunohistochemical electron photomicrographs. CONCLUSIONS--Fibronectin covering the surface of the articular cartilage may have a role in joint lubrication and protection of the cartilage by binding with the collagenous matrix and hyaluronic acid in synovial fluid. Chondroitin sulphates may act as a charge barrier in close relationship with the collagen fibrils in the deeper lamina. Significant alteration in these functions may be one of the first causal steps leading to destruction of the articular cartilage. Images PMID:8546534

  20. Arthroscopic laser in intra-articular knee cartilage disorders

    NASA Astrophysics Data System (ADS)

    Nosir, Hany R.; Siebert, Werner E.

    1996-12-01

    Different assemblies have endeavored to develop arthroscopic laser surgery. Various lasers have been tried in the treatment of orthopaedic problems, and the most useful has turned out to be the Hol-YAG laser 2.1 nm which is a near- contact laser. By using the laser as a powerful tool, and cutting back on the power level, one is able to better achieve the desired treatment effect. Clinical studies to evaluating the role of the laser in different arthroscopic knee procedures, comparing to conventional techniques, showed that the overall outcome attains a momentous confidence level which is shifted to the side of the laser versus the conventional for all maneuvers, barring meniscectomy where there is not perceiving disparity between laser versus the conventional. Meniscectomy continues to be one of the most commonly performed orthopaedic procedures. Laser provides a single tool which can ablate and debride meniscal rims with efficiency and safety. Chondroplasty can also be accomplished with ease using defocused laser energy. Both lateral release and soft tissue cermilization benefit from the cutting effect of laser along with its hemostatic effect. Synovial reduction with a defocused laser is also easily accomplished. By one gadget, one can cut, ablate, smooth, coagulate, congeal and with authentic tissue depth control The future of laser arthroscopic surgery lies in its ability to weld or repair tissues. Our research study has shown that laser activated photoactive dyes can produce a molecular bonding of collagen fibers, and therefore a repair 'weld' can be achieved with both meniscal tissues and with articular cartilage lesions.

  1. Permeation of dimethyl sulfoxide into articular cartilage at subzero temperatures.

    PubMed

    Zhang, Shao-Zhi; Yu, Xiao-Yi; Chen, Guang-Ming

    2012-03-01

    Osteochondral allografting has been proved to be a useful method to treat diseased or damaged areas of joint surfaces. Operational long-term stocks of grafts which supply a buffer between procurement and utilization would contribute to the commercialization or industrialization of this technology. Vitrification has been thought to be a promising method for successful preservation of articular cartilage (AC), but high concentration cryoprotectants (CPAs) are used which may cause high cellular toxicity. An effective way to reduce CPA toxicity is to increase CPA concentration gradually while the temperature is lowered. Understanding the mechanism of CPA permeation at subzero temperatures is important for designing the cryopreservation protocol. In this research, the permeation of dimethyl sulfoxide (Me(2)SO) in ovine AC at subzero temperatures was studied experimentally. Pretreated AC discs were exposed in Me(2)SO solutions for different time (0, 5, 15, 30, 50, 80, and 120 min) at three temperature levels (-10, -20, and -30 °C). The Me(2)SO concentration within the tissue was determined by ultraviolet (UV) spectrophotometry. The diffusion coefficients were estimated to be 0.85×10(-6), 0.48×10(-6), and 0.27×10(-6) cm(2)/s at -10, -20, and -30 °C, respectively, and the corresponding activation energy was 29.23 kJ/mol. Numerical simulation was performed to compare two Me(2)SO addition protocols, and the results demonstrated that the total loading duration could be effectively reduced with the knowledge of permeation kinetics. PMID:22374614

  2. Modeling the transport of cryoprotective agents in articular cartilage for cryopreservation

    NASA Astrophysics Data System (ADS)

    Torqabeh, Alireza Abazari

    Loading vitrifiable concentrations of cryoprotective agents is an important step for cryopreservation of biological tissues by vitrification for research and transplantation purposes. This may be done by immersing the tissue in a cryoprotective agent (CPA) solution, and increasing the concentration, continuously or in multiple steps, and simultaneously decreasing the temperature to decrease the toxicity effects of the cryoprotective agent on the tissue cellular system. During cryoprotective agent loading, osmotic water movement from the tissue to the surrounding solution, and the resultant tissue shrinkage and stress-strain in the tissue matrix as well as on the cellular system can significantly alter the outcome of the cryopreservation protocol. In this thesis, a biomechanical model for articular cartilage is developed to account for the transport of the cryoprotective agent, the nonideal-nondilute properties of the vitrifiable solutions, the osmotic water movement and the resultant tissue shrinkage and stress-strain in the tissue matrix, and the osmotic volume change of the chondrocytes, during cryoprotective agent loading in the cartilage matrix. Four essential transport parameters needed for the model were specified, the values of which were obtained uniquely by fitting the model to experimental data from porcine articular cartilage. Then, it was shown that using real nonuniform initial distributions of water and fixed charges in cartilage, measured separately in this thesis using MRI, in the model can significantly affect the model predictions. The model predictions for dimethyl sulfoxide diffusion in porcine articular cartilage were verified by comparing to spatially and temporally resolved measurements of dimethyl sulfoxide concentration in porcine articular cartilage using a spectral MRI technique, developed for this purpose and novel to the field of cryobiology. It was demonstrated in this thesis that the developed mathematical model provides a novel tool

  3. Effects of Chondroitinase ABC-Mediated Proteoglycan Digestion on Decellularization and Recellularization of Articular Cartilage

    PubMed Central

    Bautista, Catherine A.; Park, Hee Jun; Mazur, Courtney M.; Aaron, Roy K.

    2016-01-01

    Articular cartilage has a limited capacity to heal itself and thus focal defects often result in the development of osteoarthritis. Current cartilage tissue engineering strategies seek to regenerate injured tissue by creating scaffolds that aim to mimic the unique structure and composition of native articular cartilage. Decellularization is a novel strategy that aims to preserve the bioactive factors and 3D biophysical environment of the native extracellular matrix while removing potentially immunogenic factors. The purpose of this study was to develop a procedure that can enable decellularization and recellularization of intact articular cartilage matrix. Full-thickness porcine articular cartilage plugs were decellularized with a series of freeze-thaw cycles and 0.1% (w/v) sodium dodecyl sulfate detergent cycles. Chondroitinase ABC (ChABC) was applied before the detergent cycles to digest glycosaminoglycans in order to enhance donor chondrocyte removal and seeded cell migration. Porcine synovium-derived mesenchymal stem cells were seeded onto the decellularized cartilage scaffolds and cultured for up to 28 days. The optimized decellularization protocol removed 94% of native DNA per sample wet weight, while collagen content and alignment were preserved. Glycosaminoglycan depletion prior to the detergent cycles increased removal of nuclear material. Seeded cells infiltrated up to 100 μm into the cartilage deep zone after 28 days in culture. ChABC treatment enhances decellularization of the relatively dense, impermeable articular cartilage by reducing glycosaminoglycan content. ChABC treatment did not appear to affect cell migration during recellularization under static, in vitro culture, highlighting the need for more dynamic seeding methods. PMID:27391810

  4. Xenogeneic transplantation of articular chondrocytes into full-thickness articular cartilage defects in minipigs: fate of cells and the role of macrophages.

    PubMed

    Niemietz, Thomas; Zass, Gesa; Hagmann, Sébastien; Diederichs, Solvig; Gotterbarm, Tobias; Richter, Wiltrud

    2014-12-01

    Xenogeneic or allogeneic chondrocytes hold great potential to build up new cartilage in vivo. However, immune rejection is a major concern for the utility of universal donor-derived cells. In order to verify the reported immune privilege of chondrocytes in vivo, the aim of this study was to assess engraftment of human articular chondrocytes (HAC) in minipig knee cartilage defects and their contribution to cartilage regeneration. HAC were transplanted matrix-assisted within two hydrogels into full-thickness cartilage defects of minipigs or implanted ectopically into immune deficient mice to assess redifferentiation capacity. At 2 and 4 weeks after surgery, cell-persistence and host cell invasion were monitored by species-specific in situ hybridization and RT-PCR. Early tissue regeneration was evaluated by histomorphometry and a modified O'Driscoll score. HAC capable of successful in vivo chondrogenic redifferentiation persisted at ectopic sites for 4 weeks in both carrier materials. Early defect regeneration involved extensive host cell invasion and a decline of HAC to less than 5 % of initial cell numbers in 6/12 defects within 2 weeks. Few clusters of persisting HAC within collagen type II-rich tissue were surrounded by porcine macrophages. Four weeks after cell transplantation, most of the defects contained well-integrated cell-rich tissue free of human cells with no apparent difference between hydrogel carriers. In summary, HAC failed to engraft in porcine articular cartilage defects despite their ability for successful in vivo redifferentiation. The co-localization of macrophages to hydrogel-implanted HAC suggests active graft rejection without evidence for an immune-privileged status of xenogeneic chondrocytes in a large animal joint. PMID:25129109

  5. Irrigating solutions used in arthroscopy and their effect on articular cartilage. An in vivo study

    SciTech Connect

    Arciero, R.A.; Little, J.S.; Liebenberg, S.P.; Parr, T.J.

    1986-11-01

    The effect of arthroscopic irrigating solutions on articular cartilage was determined by the use of an animal model. Rabbit knee joints were irrigated continuously for two hours with either normal saline, Ringer's lactate, or sterile water. Subsequently, the rate of incorporation of /sup 35/SO/sub 4/ by articular cartilage was used to measure the effect of the irrigants on chondrocyte metabolism. In addition, the irrigated groups were compared to an unirrigated control group. There was no significant difference in /sup 35/SO/sub 4/ incorporation between the groups. This suggested that none of the irrigating solutions used in this study adversely affected articular cartilage function. On the basis of these findings, it appears that normal saline, Ringer's lactate, and sterile water can be safely used as irrigating solutions during most arthroscopic procedures.

  6. Alterations in endogenous osteogenic protein-1 with degeneration of human articular cartilage.

    PubMed

    Merrihew, Charis; Kumar, Bhavna; Heretis, Katherine; Rueger, David C; Kuettner, Klaus E; Chubinskaya, Susan

    2003-09-01

    A synchronized balance between synthesis and breakdown of extracellular matrix (ECM) molecules in normal articular cartilage is disturbed in osteoarthritis (OA). The focus of our study is the anabolic factor, osteogenic protein-1 (OP-1) that is expressed in articular cartilage and is able to induce the synthesis of ECM components. The major aim was to investigate both qualitatively and quantitatively endogenous OP-1 in normal, degenerative, and OA cartilage. Normal and degenerative cartilage was obtained at autopsies from femoral condyles of human organ donors with no documented history of joint disease; OA cartilage was obtained from patients undergoing joint arthroplasty. Appearance of donor cartilage was evaluated by Collins scale, where normal cartilage is assigned grades 0-1, and degenerated cartilage is assigned grades 2-4. OP-1 mRNA expression was assessed by RT-PCR; OP-1 protein (pro- and active forms) was qualitatively analyzed by Western blotting and quantified by OP-1 ELISA. The highest levels of OP-1 expression (mRNA and protein) were detected in normal cartilage of grade 0. The concentration of OP-1 protein was about 50 ng per gram cartilage dry weight. With the progression of cartilage degeneration (increased Collins grades and OA) OP-1 protein was down-regulated up to 9-fold. These changes affected primarily the active form of OP-1. OP-1 message also declined in cartilages with the increase of degenerative changes. In conclusion, an overall decrease in endogenous OP-1 in degenerated and OA tissue suggests that OP-1 could be one of the factors responsible for normal homeostasis and matrix integrity in cartilage. PMID:12919879

  7. Single cell sorting identifies progenitor cell population from full thickness bovine articular cartilage

    PubMed Central

    Yu, Yin; Zheng, Hongjun; Buckwalter, Joseph A.; Martin, James A.

    2014-01-01

    Objective To date, no approved clinical intervention successfully prevents the progressive degradation of injured articular cartilage that leads to osteoarthritis (OA). Stem/progenitor cell populations within tissues of diarthrodial joint have shown their therapeutic potential in treating OA. However, this potential has not been fully realized due in part to the heterogeneity of these subpopulations. Characterization of clonal populations derived from a single cell may help identify more homogenous stem/progenitor populations within articular cartilage. Moreover, chondrogenic potential of clonal populations from different zones could be further examined to elucidate their differential roles in maintaining articular cartilage homeostasis. Method We combined FACS (Fluorescence-activated cell sorting) and clonogenicity screening to identify stem/progenitor cells cloned from single cells. High-efficiency colony-forming cells (HCCs) were isolated, and evaluated for stem/progenitor cell characteristics. HCCs were also isolated from different zones of articular cartilage. Their function was compared by lineage-specific gene expression, and differentiation potential. Results A difference in colony-forming efficiency was observed in terms of colony sizes. HCCs were highly clonogenic and multipotent, and overexpressed stem/progenitor cell markers. Also, proliferation and migration associated genes were over-expressed in HCCs. HCCs showed zonal differences with deep HCCs more chondrogenic and osteogenic than superficial HCCs. Conclusion Our approach is a simple yet practical way to identify homogeneous stem/progenitor cell populations with clonal origin. The discovery of progenitor cells demonstrates the intrinsic self-repairing potential of articular cartilage. Differences in differentiation potential may represent the distinct roles of superficial and deep zone stem/progenitor cells in the maintenance of articular cartilage homeostasis. PMID:25038490

  8. [Remodeling of the articular cartilage during the replacement of its defect by a biocomposite material].

    PubMed

    Bogatov, V B; Zeinalov, P V; Liubun', G P; Kozadayev, M N; Matveyeva, O V; Sal'kovskiy, Yu Ye; Radzhabov, A M; Puchinyian, D M

    2015-01-01

    The regenerative capacity of articular cartilage was studied in animals in which its defects were replaced by biocomposite materials based on polycaprolactone in combination with hydroxyapatite. Six specimens of the material were used, which consisted of different proportions of these polymers. In the experiment on sheep (n = 6) it was found that these biocomposite materials were replaced by hyaline-like cartilage during healing of artificially created defects in the articular cartilage of the knee joint, while the ratio of composite components had no effect on the quality of the regenerates formed. These results support the view of a possible application of biocomposite materials in the treatment of degenerative and traumatic lesions of hyaline cartilage. PMID:25958731

  9. [Basophilic line of the articular cartilage in normal and various pathological states].

    PubMed

    Gongadze, L R

    1987-04-01

    Epiphyses of long tubular bones in the man and animals of various age, as well as experimental material of the adjuvant arthritis, with special reference to the basal part of the articular cartilage have been studied by means of histological, histochemical and histometrical methods. The structural-chemical organization of the basophilic line (tidemark) of the articular cartilage ensures its barrier role and participation in regulating selective permeability. Reconstruction of the tidemark in the process of physiological ageing and in cases of the articular pathology is aimed to preserve its integrity and in this way a complete differentiation of the noncalcified and calcified structures is secured. Disturbance of the basophilic line results in changes of the articular selective permeability, in invasion of vessels and structural elements of the bone marrow, and in development of profound distrophic and destructive changes of the cartilage--in deforming artrosis. Deflations in the structural-chemical organization of the tidemark indicate certain disturbances in the state of the system articular cartilage--subchondral bone. These data can be of prognostic importance. PMID:3606408

  10. Degenerative lesions in the articular cartilage after meniscectomy: preliminary experimental study in dogs.

    PubMed

    Berjon, J J; Munuera, L; Calvo, M

    1991-03-01

    Articular cartilage degeneration was studied in an experimental model including 68 knees of adult dogs on which five different types of medial meniscectomy had been performed with a followup period of 10 to 450 days. The results were assessed by macroscopic, radiologic, and histologic methods. The degenerative lesions increased proportionally to the amount of meniscal tissue resected and the duration of observation. These lesions proved to be more intense at the tibial plateau compared to the femoral condyle. For both joint surfaces the predominant location was the central zone. Considering the degenerative process by the articular cartilage after total meniscectomy, maximum preservation of meniscal tissue is recommended. PMID:2002520

  11. The effects of joint immobilization on articular cartilage of the knee in previously exercised rats

    PubMed Central

    Maldonado, Diogo Correa; da Silva, Marcelo Cavenaghi Pereira; Neto, Semaan El-Razi; Souza, Mônica Rodrigues; Souza, Romeu Rodrigues

    2013-01-01

    Studies have determined the effects of joint immobilization on the articular cartilage of sedentary animals, but we are not aware of any studies reporting the effects of joint immobilization in previously trained animals. The objective of the present study was to determine whether exercise could prevent degeneration of the articular cartilage that accompanies joint immobilization. We used light microscopy to study the thickness, cell density, nuclear size, and collagen density of articular cartilage of the femoral condyle of Wistar rats subjected to aerobic physical activity on an adapted treadmill five times per week. Four groups of Wistar rats were used: a control group (C), an immobilized group (I), an exercised group (E), and an exercised and then immobilized group (EI). The right knee joints from rats in groups I and EI were immobilized at 90 °C of flexion using a plastic cast for 8 weeks. Cartilage thickness decreased significantly in group I (mean, 120.14 ± 15.6 μm, P < 0.05), but not in group EI (mean, 174 ± 2.25), and increased significantly in group E (mean, 289.49 ± 9.15) compared with group C (mean, 239.20 ± 6.25). The same results were obtained for cell density, nuclear size, and collagen density (in all cases, P < 0.05). We concluded that exercise can prevent degenerative changes in femoral articular cartilage caused by immobilization of the knee joint. PMID:23480127

  12. Quantitative Assessment of Articular Cartilage Morphology via EPIC-μCT

    PubMed Central

    Xie, Liqin; Lin, Angela S.P.; Levenston, Marc E.; Guldberg, Robert E.

    2009-01-01

    Summary Objective The objective of the present study was to validate the ability of EPIC-μCT to nondestructively assess cartilage morphology in the rat model. Design An appropriate contrast agent (Hexabrix) concentration and incubation time for equilibration were determined for reproducible segmentation of femoral articular cartilage from contrast-enhanced μCT scans. Reproducibility was evaluated by triplicate scans of six femora, and the measured articular cartilage thickness was independently compared to thickness determined from needle probe testing and histology. The validated technique was then applied to quantify age-related differences in articular cartilage morphology between 4, 8, and 16-week old (n=5 each) male Wistar rats. Results A 40% Hexabrix/60% PBS solution with 30 minute incubation was optimal for segmenting cartilage from the underlying bone tissue and other soft tissues in the rat model. High reproducibility was indicated by the low coefficient of variation (1.7-2.5%) in cartilage volume, thickness and surface area. EPIC-μCT evaluation of thickness showed a strong linear relationship and good agreement with both needle probing (r2=0.95, slope=0.81, p<0.01, mean difference 11±22μm, n=43) and histology (r2=0.99, slope=0.97, p<0.01, mean difference 12±10μm, n=30). Cartilage volume and thickness significantly decreased with age while surface area significantly increased. Conclusion EPIC-μCT imaging has the ability to nondestructively evaluate three-dimensional articular cartilage morphology with high precision and accuracy in a small animal model. PMID:18789727

  13. Does Low-intensity pulsed ultrasound treatment repair articular cartilage injury? A rabbit model study

    PubMed Central

    2014-01-01

    Background Low-intensity pulsed ultrasound (LIPUS) regiment has been used to treat fractures with non-union and to promote bone union in general. The effect of LIPUS on articular cartilage metabolism has been characterized. Yet, the effect of LIPUS to repair articular cartilage injury remains unclear in vivo. Methods We designed a study to investigate the effect of LIPUS on articular cartilage repairing in a rabbit severe cartilage injury model. Eighteen rabbits were divided into three groups: Sham-operated group, operated group without-LIPUS-treatment, operated group with-LIPUS-treatment (a daily 20-minute treatment for 3 months). Full-thickness cartilage defects were surgically created on the right side distal femoral condyle without intending to penetrate into the subchondral bone, which mimicked severe chondral injury. MR images for experimental joints, morphology grading scale, and histopathological Mankin score were evaluated. Results The preliminary results showed that the operated groups with-LIPUS-treatment and without-LIPUS-treatment had significantly higher Mankin score and morphological grading scale compared with the sham-operated group. However, there was no significant difference between the with-LIPUS-treatment and without-LIPUS-treatment groups. Cartilage defects filled with proliferative tissue were observed in the with-LIPUS-treatment group grossly and under MR images, however which presented less up-take under Alcian blue stain. Furthermore, no new deposition of type II collagen or proliferation of chondrocyte was observed over the cartilage defect after LIPUS treatment. Conclusion LIPUS has no significant therapeutic potential in treating severe articular cartilage injury in our animal study. PMID:24507771

  14. Effect of pulsed electromagnetic fields on proteoglycan biosynthesis of articular cartilage is age dependent

    PubMed Central

    Bobacz, K; Graninger, W B; Amoyo, L; Smolen, J S

    2006-01-01

    Objective To investigate the effects of a pulsed electromagnetic field (EMF) on articular cartilage matrix biosynthesis with regard to age and cartilage damage using a matrix depleted cartilage explant model. Methods Cartilage explants were obtained from metacarpophalangeal joints of calves and adult cows. After depletion of the extracellular matrix by trypsin digestion, samples were maintained in serum‐free basal medium with and without the addition of interleukin 1β (IL1β). Half the samples were subjected to an EMF for 24 minutes daily; the other half were left untreated. Undigested and untreated explants served as negative controls. After 7 days, biosynthesis of matrix macromolecules was assessed by [35S]sulphate incorporation and values were normalised to hydroxyproline content. Results The EMF increased matrix macromolecule synthesis in undigested, untreated explants (p<0.009). In matrix depleted samples the EMF had no stimulatory effect on proteoglycan biosynthesis. IL1β significantly decreased the de novo synthesis of matrix macromolecules (p<0.00004) in young and adult samples, but an EMF partly counteracted this inhibitory effect in cartilage samples from young, but not old animals. Conclusion EMF promoted matrix macromolecule biosynthesis in intact tissue explants but had no stimulatory effect on damaged articular cartilage. The supressive effects of IL1β were partially counteracted by EMF exposure, exclusively in cartilage derived from young animals. An EMF has age dependent chondroprotective but not structure modifying properties when cartilage integrity is compromised. PMID:16769781

  15. 3D Hydrogel Scaffolds for Articular Chondrocyte Culture and Cartilage Generation

    PubMed Central

    Yang, Fan; Bhutani, Nidhi

    2015-01-01

    Human articular cartilage is highly susceptible to damage and has limited self-repair and regeneration potential. Cell-based strategies to engineer cartilage tissue offer a promising solution to repair articular cartilage. To select the optimal cell source for tissue repair, it is important to develop an appropriate culture platform to systematically examine the biological and biomechanical differences in the tissue-engineered cartilage by different cell sources. Here we applied a three-dimensional (3D) biomimetic hydrogel culture platform to systematically examine cartilage regeneration potential of juvenile, adult, and osteoarthritic (OA) chondrocytes. The 3D biomimetic hydrogel consisted of synthetic component poly(ethylene glycol) and bioactive component chondroitin sulfate, which provides a physiologically relevant microenvironment for in vitro culture of chondrocytes. In addition, the scaffold may be potentially used for cell delivery for cartilage repair in vivo. Cartilage tissue engineered in the scaffold can be evaluated using quantitative gene expression, immunofluorescence staining, biochemical assays, and mechanical testing. Utilizing these outcomes, we were able to characterize the differential regenerative potential of chondrocytes of varying age, both at the gene expression level and in the biochemical and biomechanical properties of the engineered cartilage tissue. The 3D culture model could be applied to investigate the molecular and functional differences among chondrocytes and progenitor cells from different stages of normal or aberrant development. PMID:26484414

  16. 3D Hydrogel Scaffolds for Articular Chondrocyte Culture and Cartilage Generation.

    PubMed

    Smeriglio, Piera; Lai, Janice H; Yang, Fan; Bhutani, Nidhi

    2015-01-01

    Human articular cartilage is highly susceptible to damage and has limited self-repair and regeneration potential. Cell-based strategies to engineer cartilage tissue offer a promising solution to repair articular cartilage. To select the optimal cell source for tissue repair, it is important to develop an appropriate culture platform to systematically examine the biological and biomechanical differences in the tissue-engineered cartilage by different cell sources. Here we applied a three-dimensional (3D) biomimetic hydrogel culture platform to systematically examine cartilage regeneration potential of juvenile, adult, and osteoarthritic (OA) chondrocytes. The 3D biomimetic hydrogel consisted of synthetic component poly(ethylene glycol) and bioactive component chondroitin sulfate, which provides a physiologically relevant microenvironment for in vitro culture of chondrocytes. In addition, the scaffold may be potentially used for cell delivery for cartilage repair in vivo. Cartilage tissue engineered in the scaffold can be evaluated using quantitative gene expression, immunofluorescence staining, biochemical assays, and mechanical testing. Utilizing these outcomes, we were able to characterize the differential regenerative potential of chondrocytes of varying age, both at the gene expression level and in the biochemical and biomechanical properties of the engineered cartilage tissue. The 3D culture model could be applied to investigate the molecular and functional differences among chondrocytes and progenitor cells from different stages of normal or aberrant development. PMID:26484414

  17. Diffusion and near-equilibrium distribution of MRI and CT contrast agents in articular cartilage.

    PubMed

    Silvast, Tuomo S; Kokkonen, Harri T; Jurvelin, Jukka S; Quinn, Thomas M; Nieminen, Miika T; Töyräs, Juha

    2009-11-21

    Charged contrast agents have been used both in vitro and in vivo for estimation of the fixed charge density (FCD) in articular cartilage. In the present study, the effects of molecular size and charge on the diffusion and equilibrium distribution of several magnetic resonance imaging (MRI) and computed tomography (CT) contrast agents were investigated. Full thickness cartilage disks (Ø = 4.0 mm, n = 64) were prepared from fresh bovine patellae. Contrast agent (gadopentetate: Magnevist((R)), gadodiamide: Omniscan, ioxaglate: Hexabrix or sodium iodide: NaI) diffusion was allowed either through the articular surface or through the deep cartilage. CT imaging of the samples was conducted before contrast agent administration and after 1, 5, 9, 16, 25 and 29 h (and with three samples after 2, 3, 4 and 5 days) diffusion using a clinical peripheral quantitative computed tomography (pQCT) instrument. With all contrast agents, the diffusion through the deep cartilage was slower when compared to the diffusion through the articular surface. With ioxaglate, gadopentetate and gadodiamide it took over 29 h for diffusion to reach the near-equilibrium state. The slow diffusion of the contrast agents raise concerns regarding the validity of techniques for FCD estimation, as these contrast agents may not reach the equilibrium state that is assumed. However, since cartilage composition, i.e. deep versus superficial, had a significant effect on diffusion, imaging of the nonequilibrium diffusion process might enable more accurate assessment of cartilage integrity. PMID:19864699

  18. Electromechanical response of articular cartilage in indentation--considerations on the determination of cartilage properties during arthroscopy.

    PubMed

    Li, L P; Herzog, W

    2005-04-01

    A finite element formulation of streaming potentials in articular cartilage was incorporated into a fibril-reinforced model using the commercial software ABAQUS. This model was subsequently used to simulate interactions between an arthroscopic probe and articular cartilage in a knee joint. Fibril reinforcement was found to account for large fluid pressure at considerable strain rates, as has been observed in un-confined compression. Furthermore, specific electromechanical responses were associated with specific changes in tissue properties that occur with cartilage degeneration. For example, the strong strain-rate dependence of the load response was only observed when the collagen network was intact. Therefore, it is possible to use data measured during arthroscopy to evaluate the degree of cartilage degeneration and the source causing changed properties. However, practical problems, such as the difficulty of controlling the speed of the hand-held probe, may greatly reduce the reliability of such evaluations. The fibril-reinforced electromechanical model revealed that high-speed transient responses were associated with the collagen network, and equilibrium response was primarily determined by proteoglycan matrix. The results presented here may be useful in the application of arthroscopic tools for evaluating cartilage degeneration, for the proper interpretation of data, and for the optimization of data collection during arthroscopy. PMID:16154872

  19. In Vivo Dynamic Deformation of Articular Cartilage in Intact Joints Loaded by Controlled Muscular Contractions.

    PubMed

    Abusara, Ziad; Von Kossel, Markus; Herzog, Walter

    2016-01-01

    When synovial joints are loaded, the articular cartilage and the cells residing in it deform. Cartilage deformation has been related to structural tissue damage, and cell deformation has been associated with cell signalling and corresponding anabolic and catabolic responses. Despite the acknowledged importance of cartilage and cell deformation, there are no dynamic data on these measures from joints of live animals using muscular load application. Research in this area has typically been done using confined and unconfined loading configurations and indentation testing. These loading conditions can be well controlled and allow for accurate measurements of cartilage and cell deformations, but they have little to do with the contact mechanics occurring in a joint where non-congruent cartilage surfaces with different material and functional properties are pressed against each other by muscular forces. The aim of this study was to measure in vivo, real time articular cartilage deformations for precisely controlled static and dynamic muscular loading conditions in the knees of mice. Fifty and 80% of the maximal knee extensor muscular force (equivalent to approximately 0.4N and 0.6N) produced average peak articular cartilage strains of 10.5±1.0% and 18.3±1.3% (Mean ± SD), respectively, during 8s contractions. A sequence of 15 repeat, isometric muscular contractions (0.5s on, 3.5s off) of 50% and 80% of maximal muscular force produced cartilage strains of 3.0±1.1% and 9.6±1.5% (Mean ± SD) on the femoral condyles of the mouse knee. Cartilage thickness recovery following mechanical compression was highly viscoelastic and took almost 50s following force removal in the static tests. PMID:26807930

  20. In Vivo Dynamic Deformation of Articular Cartilage in Intact Joints Loaded by Controlled Muscular Contractions

    PubMed Central

    Abusara, Ziad; Von Kossel, Markus; Herzog, Walter

    2016-01-01

    When synovial joints are loaded, the articular cartilage and the cells residing in it deform. Cartilage deformation has been related to structural tissue damage, and cell deformation has been associated with cell signalling and corresponding anabolic and catabolic responses. Despite the acknowledged importance of cartilage and cell deformation, there are no dynamic data on these measures from joints of live animals using muscular load application. Research in this area has typically been done using confined and unconfined loading configurations and indentation testing. These loading conditions can be well controlled and allow for accurate measurements of cartilage and cell deformations, but they have little to do with the contact mechanics occurring in a joint where non-congruent cartilage surfaces with different material and functional properties are pressed against each other by muscular forces. The aim of this study was to measure in vivo, real time articular cartilage deformations for precisely controlled static and dynamic muscular loading conditions in the knees of mice. Fifty and 80% of the maximal knee extensor muscular force (equivalent to approximately 0.4N and 0.6N) produced average peak articular cartilage strains of 10.5±1.0% and 18.3±1.3% (Mean ± SD), respectively, during 8s contractions. A sequence of 15 repeat, isometric muscular contractions (0.5s on, 3.5s off) of 50% and 80% of maximal muscular force produced cartilage strains of 3.0±1.1% and 9.6±1.5% (Mean ± SD) on the femoral condyles of the mouse knee. Cartilage thickness recovery following mechanical compression was highly viscoelastic and took almost 50s following force removal in the static tests. PMID:26807930

  1. 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. PMID:27324118

  2. Mesenchymal progenitor cell markers in human articular cartilage: normal distribution and changes in osteoarthritis

    PubMed Central

    Grogan, Shawn P; Miyaki, Shigeru; Asahara, Hiroshi; D'Lima, Darryl D; Lotz, Martin K

    2009-01-01

    Introduction Recent findings suggest that articular cartilage contains mesenchymal progenitor cells. The aim of this study was to examine the distribution of stem cell markers (Notch-1, Stro-1 and VCAM-1) and of molecules that modulate progenitor differentiation (Notch-1 and Sox9) in normal adult human articular cartilage and in osteoarthritis (OA) cartilage. Methods Expression of the markers was analyzed by immunohistochemistry (IHC) and flow cytometry. Hoechst 33342 dye was used to identify and sort the cartilage side population (SP). Multilineage differentiation assays including chondrogenesis, osteogenesis and adipogenesis were performed on SP and non-SP (NSP) cells. Results A surprisingly high number (>45%) of cells were positive for Notch-1, Stro-1 and VCAM-1 throughout normal cartilage. Expression of these markers was higher in the superficial zone (SZ) of normal cartilage as compared to the middle zone (MZ) and deep zone (DZ). Non-fibrillated OA cartilage SZ showed reduced Notch-1 and Sox9 staining frequency, while Notch-1, Stro-1 and VCAM-1 positive cells were increased in the MZ. Most cells in OA clusters were positive for each molecule tested. The frequency of SP cells in cartilage was 0.14 ± 0.05% and no difference was found between normal and OA. SP cells displayed chondrogenic and osteogenic but not adipogenic differentiation potential. Conclusions These results show a surprisingly high number of cells that express putative progenitor cell markers in human cartilage. In contrast, the percentage of SP cells is much lower and within the range of expected stem cell frequency. Thus, markers such as Notch-1, Stro-1 or VCAM-1 may not be useful to identify progenitors in cartilage. Instead, their increased expression in OA cartilage implicates involvement in the abnormal cell activation and differentiation process characteristic of OA. PMID:19500336

  3. Age related changes and osteochondrosis in swine articular and epiphyseal cartilage: light ane electron microscopy.

    PubMed Central

    Bhatnagar, R; Christian, R G; Nakano, T; Aherne, F X; Thompson, J R

    1981-01-01

    Age related changes and osteochondrosis in swine were studied using light microscopy and electron microscopy in articular cartilage and light microscopy and epiphyseal cartilage of swine from three days to 30 weeks of age. Thickness, cellularity and vascularity of both the epiphyseal and articular cartilage, decreased as the swine aged. Osteochondrotic changes included formation of "plugs" of cartilage indicating localized failure of ossification and separation and space formation in epiphyseal cartilage. Eosinophilic streaks and space formation in epiphyseal cartilage was observed in relation to epiphyseal separation. Electron microscopy showed a continuous fibrillar layer on the surface of the cartilage corresponding to the lamina splendens of light microscopy. This layer increased in the thickness and showed accumulation of amorphous material between the fibrils with aging. In the matrix, the orientation and distribution of the collagen fibers changed with growth and thicker fibers with clear sub banding were more common in older age groups. Also, necrotic cells, glycogen containing bodies and cellular debris were noticed in the matrix of normal cartilage in old animals. Chondrocytes in the younger cartilage showed accumulation of organelles responsible for protein synthesis; while Golgi bodies, vesicles, lysosomes, well developed foot processes and other inclusions were noticed in older cartilage. Cartilage erosions had a clumped and disrupted lamina splendens on the surface and electron lucent patches in the ground substances of the matrix and chondrocyte cytoplasm. Images Fig. 1. Fig. 2 and 3. Fig. 4. Fig. 5. Fig. 6. Fig. 7. Fig. 8. Fig. 9. Fig. 10 and 11. Fig. 12. Fig. 13. Fig. 14. Fig. 15. Fig. 16. Fig. 17. Fig. 18. PMID:7260732

  4. Glucosamine:chondroitin or ginger root extract have little effect on articular cartilage in swine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sows are culled at a high rate from breeding herds due to musclo-skeletal problems and lameness. Research in our laboratory has shown that even first-parity sows have significant amounts of osteochondritic lesions of their articular cartilage. Glusoamine chondroitin and ginger root extract have both...

  5. Articular Cartilage Increases Transition Zone Regeneration in Bone-tendon Junction Healing

    PubMed Central

    Qin, Ling; Lee, Kwong Man; Leung, Kwok Sui

    2008-01-01

    The fibrocartilage transition zone in the direct bone-tendon junction reduces stress concentration and protects the junction from failure. Unfortunately, bone-tendon junctions often heal without fibrocartilage transition zone regeneration. We hypothesized articular cartilage grafts could increase fibrocartilage transition zone regeneration. Using a goat partial patellectomy repair model, autologous articular cartilage was harvested from the excised distal third patella and interposed between the residual proximal two-thirds bone fragment and tendon during repair in 36 knees. We evaluated fibrocartilage transition zone regeneration, bone formation, and mechanical strength after repair at 6, 12, and 24 weeks and compared them with direct repair. Autologous articular cartilage interposition resulted in more fibrocartilage transition zone regeneration (69.10% ± 14.11% [mean ± standard deviation] versus 8.67% ± 7.01% at 24 weeks) than direct repair at all times. There was no difference in the amount of bone formation and mechanical strength achieved. Autologous articular cartilage interposition increases fibrocartilage transition zone regeneration in bone-tendon junction healing, but additional research is required to ascertain the mechanism of stimulation and to establish the clinical applicability. PMID:18987921

  6. The lamina splendens of articular cartilage is an artefact of phase contrast microscopy.

    PubMed

    Aspden, R M; Hukins, D W

    1979-11-30

    The so-called lamina splendens of articular cartilage is shown to be a characteristic of phase contrast microscopy; this technique provides no evidence for an anatomically distinct surface layer. Fresnel diffraction occurs at edges separating regions of different refractive indices. These diffraction effects, when viewed under phase contrast, lead to the appearance of a bright line along the edge. PMID:42065

  7. 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.

  8. T2* mapping of articular cartilage: current status of research and first clinical applications.

    PubMed

    Andreisek, Gustav; Weiger, Markus

    2014-01-01

    T2* mapping is a relatively new method for the compositional assessment of the articular cartilage. Typically, a multigradient echo or an ultrashort echo time imaging technique with a range of short and very short echo times is used. In most studies, imaging is performed at a high field strength, that is, 3 and 7 T. Postprocessing includes exponential fitting of relaxation decay and manual region-of-interest-based measurements of T2* times on T2* maps. Detailed analyses of T2* times of articular cartilage have shown distinct T2* components with shorter and longer T2* times. Moreover, there is a zonal distribution with a significant depthwise gradient of T2*, with relatively short times near the osteochondral junction and relatively long times at the cartilage's surface. T2* times of normal articular cartilage at the knee are, when averaged over the whole cartilage thickness and using monoexponential fitting, approximately 20 milliseconds. The results of recent studies have shown a good test-retest as well as interreader and intrareader reliabilities for T2* mapping. This article provides a descriptive review of the current literature, briefly discusses the technique itself, and provides an outlook on future research questions and possible clinical applications. PMID:24056113

  9. Topographical variations of the strain-dependent zonal properties of tibial articular cartilage by microscopic MRI.

    PubMed

    Lee, Ji Hyun; Badar, Farid; Kahn, David; Matyas, John; Qu, Xianggui; Chen, Christopher T; Xia, Yang

    2014-06-01

    The topographical variations of the zonal properties of canine articular cartilage over the medial tibia were evaluated as the function of external loading by microscopic magnetic resonance imaging (µMRI). T2 and T1 relaxation maps and GAG (glycosaminoglycan) images from a total of 70 specimens were obtained with and without the mechanical loading at 17.6 µm depth resolution. In addition, mechanical modulus and water content were measured from the tissue. For the bulk without loading, the means of T2 at magic angle (43.6 ± 8.1 ms), absolute thickness (907.6 ± 187.9 µm) and water content (63.3 ± 9.3%) on the meniscus-covered area were significantly lower than the means of T2 at magic angle (51.1 ± 8.5 ms), absolute thickness (1251.6 ± 218.4 µm) and water content (73.2 ± 5.6%) on the meniscus-uncovered area. However GAG (86.0 ± 15.3 mg/ml) on the covered area was significantly higher than GAG (70.0 ± 8.8 mg/ml) on the uncovered area. Complex relationships were found in the tissue properties as the function of external loading. The tissue parameters in the superficial zone changed more profoundly than the same properties in the radial zone. The tissue parameters in the meniscus-covered areas changed differently when comparing with the same parameters in the uncovered areas. This project confirms that the load-induced changes in the molecular distribution and structure of cartilage are both depth-dependent and topographically distributed. Such detailed knowledge of the tibial layer could improve the early detection of the subtle softening of the cartilage that will eventually lead to the clinical diseases such as osteoarthritis. PMID:24559385

  10. Biphasic indentation of articular cartilage--II. A numerical algorithm and an experimental study.

    PubMed

    Mow, V C; Gibbs, M C; Lai, W M; Zhu, W B; Athanasiou, K A

    1989-01-01

    Part I (Mak et al., 1987, J. Biomechanics 20, 703-714) presented the theoretical solutions for the biphasic indentation of articular cartilage under creep and stress-relaxation conditions. In this study, using the creep solution, we developed an efficient numerical algorithm to compute all three material coefficients of cartilage in situ on the joint surface from the indentation creep experiment. With this method we determined the average values of the aggregate modulus. Poisson's ratio and permeability for young bovine femoral condylar cartilage in situ to be HA = 0.90 MPa, vs = 0.39 and k = 0.44 x 10(-15) m4/Ns respectively, and those for patellar groove cartilage to be HA = 0.47 MPa, vs = 0.24, k = 1.42 x 10(-15) m4/Ns. One surprising finding from this study is that the in situ Poisson's ratio of cartilage (0.13-0.45) may be much less than those determined from measurements performed on excised osteochondral plugs (0.40-0.49) reported in the literature. We also found the permeability of patellar groove cartilage to be several times higher than femoral condyle cartilage. These findings may have important implications on understanding the functional behavior of cartilage in situ and on methods used to determine the elastic moduli of cartilage using the indentation experiments. PMID:2613721

  11. Modeling and Simulation of the Effects of Cyclic Loading on Articular Cartilage Lesion Formation

    PubMed Central

    Wang, Xiayi; Ayati, Bruce P.; Brouillete, Marc J.; Graham, Jason M.; Ramakrishnan, Prem S.; Martin, James A.

    2015-01-01

    We present a model of articular cartilage lesion formation to simulate the effects of cyclic loading. This model extends and modifies the reaction-diffusion-delay model by Graham et al. [20] for the spread of a lesion formed though a single traumatic event. Our model represents “implicitly” the effects of loading, meaning through a cyclic sink term in the equations for live cells. Our model forms the basis for in silico studies of cartilage damage relevant to questions in osteoarthritis, for example, that may not be easily answered through in vivo or in vitro studies. Computational results are presented that indicate the impact of differing levels of EPO on articular cartilage lesion abatement. PMID:24753483

  12. Regeneration of Articular Cartilage in Lizard Knee from Resident Stem/Progenitor Cells

    PubMed Central

    Alibardi, Lorenzo

    2015-01-01

    The epiphysis of femur and tibia in the lizard Podarcis muralis can extensively regenerate after injury. The process involves the articular cartilage and metaphyseal (growth) plate after damage. The secondary ossification center present between the articular cartilage and the growth plate is replaced by cartilaginous epiphyses after about one month of regeneration at high temperature. The present study analyzes the origin of the chondrogenic cells from putative stem cells located in the growing centers of the epiphyses. The study is carried out using immunocytochemistry for the detection of 5BrdU-labeled long retaining cells and for the localization of telomerase, an enzyme that indicates stemness. The observations show that putative stem cells retaining 5BrdU and positive for telomerase are present in the superficial articular cartilage and metaphyseal growth plate located in the epiphyses. This observation suggests that these areas represent stem cell niches lasting for most of the lifetime of lizards. In healthy long bones of adult lizards, the addition of new chondrocytes from the stem cells population in the articular cartilage and the metaphyseal growth plate likely allows for slow, continuous longitudinal growth. When the knee is injured in the adult lizard, new populations of chondrocytes actively producing chondroitin sulfate proteoglycan are derived from these stem cells to allow for the formation of completely new cartilaginous epiphyses, possibly anticipating the re-formation of secondary centers in later stages. The study suggests that in this lizard species, the regenerative ability of the epiphyses is a pre-adaptation to the regeneration of the articular cartilage. PMID:26340619

  13. Investigation of techniques for the measurement of articular cartilage surface roughness.

    PubMed

    Ghosh, Siddharth; Bowen, James; Jiang, Kyle; Espino, Daniel M; Shepherd, Duncan E T

    2013-01-01

    Articular cartilage is the bearing surface of synovial joints and plays a crucial role in the tribology to enable low friction joint movement. A detailed understanding of the surface roughness of articular cartilage is important to understand how natural joints behave and the parameters required for future joint replacement materials. Bovine articular cartilage on bone samples was prepared and the surface roughness was measured using scanning electron microscopy stereoscopic imaging at magnifications in the range 500× to 2000×. The surface roughness (two-dimensional, R(a), and three-dimensional, S(a)) of each sample was then measured using atomic force microscopy (AFM). For stereoscopic imaging the surface roughness was found to linearly increase with increasing magnification. At a magnification of 500× the mean surface roughness, R(a), was in the range 165.4±5.2 nm to 174±39.3 nm; total surface roughness S(a) was in the range 183-261 nm. The surface roughness measurements made using AFM showed R(a) in the range 82.6±4.6 nm to 114.4±44.9 nm and S(a) in the range 86-136 nm. Values obtained using SEM stereo imaging were always larger than those obtained using AFM. Stereoscopic imaging can be used to investigate the surface roughness of articular cartilage. The variations seen between measurement techniques show that when making comparisons between the surface roughness of articular cartilage it is important that the same technique is used. PMID:22771276

  14. Interaction of strain and interleukin-1 in articular cartilage: effects, on proteoglycan synthesis in chondrocytes

    PubMed Central

    Gassner, Robert J.; Buckley, Michael J.; Studer, Rebecca K.; Evans, Chris H.; Agarwal, Sudha

    2016-01-01

    In temporomandibular joint disorders, the release of proinflammatory cytokines such as interleukin-1 (IL-1) initiates an inflammatory process disrupting cartilage homeostasis, ultimately leading to cartilage destruction. Additionally, mechanical stimuli affect articular chondrocyte metabolism. While articular chondrocytes generate nitric oxide (NO) in the presence of IL-1 proteoglycan synthesis is consecutively suppressed. The purpose of this study was to assess the effects of proinflammatory cytokines and mechanical strain in the form of cyclic tensile stretch on proteoglycan synthesis in chondrocytes, as compared to the NO competitive inhibitor L-N-monomethyl arginine (LMA), and to assess whether this effect is secondarily related to the activity of growth factors such as transforming growth factor beta (TGF-β). Lapine articular chondrocytes were exposed to one of four different treatment regimens: no cyclic tensile stretch, IL-1, cyclic tensile stretch, or IL-1 plus cyclic tensile stretch. NO production was determined as medium nitrite accumulation. TGF-β-bioactivity in chondrocyte conditioned medium was measured with the mink-lung epithelial cell bioassay. Proteoglycan synthesis was measured as the incorporation of 35-[S]-sodium sulfate into macromolecules separated from unincorporated label by gel filtration on PD-10 columns. In resting chondrocyte cultures, only baseline levels of NO were measured and the application of stretch for 24 h did not affect NO production. Addition of IL-1 provoked a large increase in NO synthesis which was abrogated in the presence of LMA. Application of stretch decreased the IL-1 induced NO synthesis, but did not modify the effect of LMA (being a competitive inhibitor of the inducible NO synthase) inhibiting IL-1 induced NO production. Glucosaminoglycan production was noted as proteoglycan synthesis showing almost no effect of cyclic stretch alone in comparison to the control condition, which correlates with the missing NO

  15. The Role of Interstitial Fluid Pressurization in Articular Cartilage Lubrication

    PubMed Central

    Ateshian, Gerard A.

    2009-01-01

    Over the last two decades, considerable progress has been reported in the field of cartilage mechanics that impacts our understanding of the role of interstitial fluid pressurization on cartilage lubrication. Theoretical and experimental studies have demonstrated that the interstitial fluid of cartilage pressurizes considerably under loading, potentially supporting most of the applied load under various transient or steady-state conditions. The fraction of the total load supported by fluid pressurization has been called the fluid load support. Experimental studies have demonstrated that the friction coefficient of cartilage correlates negatively with this variable, achieving remarkably low values when the fluid load support is greatest. A theoretical framework that embodies this relationship has been validated against experiments, predicting and explaining various outcomes, and demonstrating that a low friction coefficient can be maintained for prolonged loading durations under normal physiological function. This paper reviews salient aspects of this topic, as well as its implications for improving our understanding of boundary lubrication by molecular species in synovial fluid and the cartilage superficial zone. Effects of cartilage degeneration on its frictional response are also reviewed. PMID:19464689

  16. Inhomogeneous Response of Articular Cartilage: A Three-Dimensional Multiphasic Heterogeneous Study

    PubMed Central

    Manzano, Sara; Armengol, Monica; J. Price, Andrew; A. Hulley, Philippa; S. Gill, Harinderjit; Doblaré, Manuel

    2016-01-01

    Articular cartilage exhibits complex mechano-electrochemical behaviour due to its anisotropy, inhomogeneity and material non-linearity. In this work, the thickness and radial dependence of cartilage properties are incorporated into a 3D mechano-electrochemical model to explore the relevance of heterogeneity in the behaviour of the tissue. The model considers four essential phenomena: (i) osmotic pressure, (ii) convective and diffusive processes, (iii) chemical expansion and (iv) three-dimensional through-the-thickness heterogeneity of the tissue. The need to consider heterogeneity in computational simulations of cartilage behaviour and in manufacturing biomaterials mimicking this tissue is discussed. To this end, healthy tibial plateaus from pigs were mechanically and biochemically tested in-vitro. Heterogeneous properties were included in the mechano-electrochemical computational model to simulate tissue swelling. The simulation results demonstrated that swelling of the heterogeneous samples was significantly lower than swelling under homogeneous and isotropic conditions. Furthermore, there was a significant reduction in the flux of water and ions in the former samples. In conclusion, the computational model presented here can be considered as a valuable tool for predicting how the variation of cartilage properties affects its behaviour, opening up possibilities for exploring the requirements of cartilage-mimicking biomaterials for tissue engineering. Besides, the model also allows the establishment of behavioural patterns of swelling and of water and ion fluxes in articular cartilage. PMID:27327166

  17. A linearized formulation of triphasic mixture theory for articular cartilage, and its application to indentation analysis.

    PubMed

    Lu, Xin L; Wan, Leo Q; Guo, X Edward; Mow, Van C

    2010-03-01

    The negative charges on proteoglycans significantly affect the mechanical behaviors of articular cartilage. Mixture theories, such as the triphasic theory, can describe quantitatively how this charged nature contributes to the mechano-electrochemical behaviors of such tissue. However, the mathematical complexity of the theory has hindered its application to complicated loading profiles, e.g., indentation or other multi-dimensional configurations. In this study, the governing equations of triphasic mixture theory for soft tissue were linearized and dramatically simplified by using a regular perturbation method and the use of two potential functions. We showed that this new formulation can be used for any axisymmetric problem, such as confined or unconfined compressions, hydraulic perfusion, and indentation. A finite difference numerical program was further developed to calculate the deformational, electrical, and flow behaviors inside the articular cartilage under indentation. The calculated tissue response was highly consistent with the data from indentation experiments (our own and those reported in the literature). It was found that the charged nature of proteoglycans can increase the apparent stiffness of the solid matrix and lessen the viscous effect introduced by fluid flow. The effects of geometric and physical properties of indenter tip, cartilage thickness, and that of the electro-chemical properties of cartilage on the resulting deformation and fluid pressure fields across the tissue were also investigated and presented. These results have implications for studying chondrocyte mechanotransduction in different cartilage zones and for tissue engineering designs or in vivo cartilage repair. PMID:19896670

  18. Synergy between Piezo1 and Piezo2 channels confers high-strain mechanosensitivity to articular cartilage

    PubMed Central

    Lee, Whasil; Leddy, Holly A.; Chen, Yong; Lee, Suk Hee; Zelenski, Nicole A.; McNulty, Amy L.; Wu, Jason; Beicker, Kellie N.; Coles, Jeffrey; Zauscher, Stefan; Grandl, Jörg; Sachs, Frederick; Liedtke, Wolfgang B.

    2014-01-01

    Diarthrodial joints are essential for load bearing and locomotion. Physiologically, articular cartilage sustains millions of cycles of mechanical loading. Chondrocytes, the cells in cartilage, regulate their metabolic activities in response to mechanical loading. Pathological mechanical stress can lead to maladaptive cellular responses and subsequent cartilage degeneration. We sought to deconstruct chondrocyte mechanotransduction by identifying mechanosensitive ion channels functioning at injurious levels of strain. We detected robust expression of the recently identified mechanosensitive channels, PIEZO1 and PIEZO2. Combined directed expression of Piezo1 and -2 sustained potentiated mechanically induced Ca2+ signals and electrical currents compared with single-Piezo expression. In primary articular chondrocytes, mechanically evoked Ca2+ transients produced by atomic force microscopy were inhibited by GsMTx4, a PIEZO-blocking peptide, and by Piezo1- or Piezo2-specific siRNA. We complemented the cellular approach with an explant-cartilage injury model. GsMTx4 reduced chondrocyte death after mechanical injury, suggesting a possible therapy for reducing cartilage injury and posttraumatic osteoarthritis by attenuating Piezo-mediated cartilage mechanotransduction of injurious strains. PMID:25385580

  19. Chondrocyte number and proteoglycan synthesis in the aging and osteoarthritic human articular cartilage

    PubMed Central

    Bobacz, K; Erlacher, L; Smolen, J; Soleiman, A; Graninger, W

    2004-01-01

    Objective: To correlate the number of chondrocytes in healthy and osteoarthritic human articular cartilage with age, and to evaluate the influence of donor age on total proteoglycan synthesis. Methods: Chondrocytes were isolated from human articular cartilage derived from hip joints with and without osteoarthritic lesions. The cell number was normalised to cartilage sample wet weight. In addition, the influence of age on chondrocyte numbers was assessed histomorphometrically. Chondrocytes were grown as monolayer cultures for seven days in a chemically defined serum-free basal medium. Total proteoglycan synthesis was measured by [35S]sulphate incorporation into newly synthesised macromolecules. Results: Chondrocyte numbers in healthy cartilage decreased significantly with advancing age (r = –0.69, p<0.0001). In contrast to healthy specimens, chondrocyte numbers were decreased in osteoarthritic cartilage irrespective of and unrelated to age, and differed markedly, by an average of 38%, from the cell numbers found in healthy individuals (p<0.0001). Regarding synthesis of matrix macromolecules, no dependence on patients' age, either in healthy or in osteoarthritic specimens, could be observed. Conclusions: Under the experimental conditions employed, chondrocytes from healthy and osteoarthritic joints synthesised comparable amounts of cartilage macromolecules, independent of age or underlying osteoarthritic disease. Thus the decrease in chondrocyte number in aging and osteoarthritic joints could be a crucial factor in limiting tissue replenishment. PMID:15547085

  20. New perspectives for articular cartilage repair treatment through tissue engineering: A contemporary review

    PubMed Central

    Musumeci, Giuseppe; Castrogiovanni, Paola; Leonardi, Rosalia; Trovato, Francesca Maria; Szychlinska, Marta Anna; Di Giunta, Angelo; Loreto, Carla; Castorina, Sergio

    2014-01-01

    In this paper review we describe benefits and disadvantages of the established methods of cartilage regeneration that seem to have a better long-term effectiveness. We illustrated the anatomical aspect of the knee joint cartilage, the current state of cartilage tissue engineering, through mesenchymal stem cells and biomaterials, and in conclusion we provide a short overview on the rehabilitation after articular cartilage repair procedures. 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 develop tissue-engineered grafts or patches to repair focal chondral and osteochondral defects, and to date several researchers aim to implement clinical application of cell-based therapies for cartilage repair. A literature review was conducted on PubMed, Scopus and Google Scholar using appropriate keywords, examining the current literature on the well-known tissue engineering methods for the treatment of knee osteoarthritis. PMID:24829869

  1. Guidelines for the Design and Conduct of Clinical Studies in Knee Articular Cartilage Repair

    PubMed Central

    Mithoefer, Kai; Saris, Daniel B.F.; Farr, Jack; Kon, Elizaveta; Zaslav, Kenneth; Cole, Brian J.; Ranstam, Jonas; Yao, Jian; Shive, Matthew; Levine, David; Dalemans, Wilfried; Brittberg, Mats

    2011-01-01

    Objective: To summarize current clinical research practice and develop methodological standards for objective scientific evaluation of knee cartilage repair procedures and products. Design: A comprehensive literature review was performed of high-level original studies providing information relevant for the design of clinical studies on articular cartilage repair in the knee. Analysis of cartilage repair publications and synopses of ongoing trials were used to identify important criteria for the design, reporting, and interpretation of studies in this field. Results: Current literature reflects the methodological limitations of the scientific evidence available for articular cartilage repair. However, clinical trial databases of ongoing trials document a trend suggesting improved study designs and clinical evaluation methodology. Based on the current scientific information and standards of clinical care, detailed methodological recommendations were developed for the statistical study design, patient recruitment, control group considerations, study endpoint definition, documentation of results, use of validated patient-reported outcome instruments, and inclusion and exclusion criteria for the design and conduct of scientifically sound cartilage repair study protocols. A consensus statement among the International Cartilage Repair Society (ICRS) and contributing authors experienced in clinical trial design and implementation was achieved. Conclusions: High-quality clinical research methodology is critical for the optimal evaluation of current and new cartilage repair technologies. In addition to generally applicable principles for orthopedic study design, specific criteria and considerations apply to cartilage repair studies. Systematic application of these criteria and considerations can facilitate study designs that are scientifically rigorous, ethical, practical, and appropriate for the question(s) being addressed in any given cartilage repair research project

  2. Accumulation of Exogenous Activated TGF-β in the Superficial Zone of Articular Cartilage

    PubMed Central

    Albro, Michael B.; Nims, Robert J.; Cigan, Alexander D.; Yeroushalmi, Kevin J.; Alliston, Tamara; Hung, Clark T.; Ateshian, Gerard A.

    2013-01-01

    It was recently demonstrated that mechanical shearing of synovial fluid (SF), induced during joint motion, rapidly activates latent transforming growth factor β (TGF-β). This discovery raised the possibility of a physiological process consisting of latent TGF-β supply to SF, activation via shearing, and transport of TGF-β into the cartilage matrix. Therefore, the two primary objectives of this investigation were to characterize the secretion rate of latent TGF-β into SF, and the transport of active TGF-β across the articular surface and into the cartilage layer. Experiments on tissue explants demonstrate that high levels of latent TGF-β1 are secreted from both the synovium and all three articular cartilage zones (superficial, middle, and deep), suggesting that these tissues are capable of continuously replenishing latent TGF-β to SF. Furthermore, upon exposure of cartilage to active TGF-β1, the peptide accumulates in the superficial zone (SZ) due to the presence of an overwhelming concentration of nonspecific TGF-β binding sites in the extracellular matrix. Although this response leads to high levels of active TGF-β in the SZ, the active peptide is unable to penetrate deeper into the middle and deep zones of cartilage. These results provide strong evidence for a sequential physiologic mechanism through which SZ chondrocytes gain access to active TGF-β: the synovium and articular cartilage secrete latent TGF-β into the SF and, upon activation, TGF-β transports back into the cartilage layer, binding exclusively to the SZ. PMID:23601326

  3. Exercise increases osteophyte formation and diminishes fibrillation following chemically induced articular cartilage injury.

    PubMed Central

    Williams, J M; Brandt, K D

    1984-01-01

    The present study shows that a treadmill exercise regimen imposed on guinea-pigs whose articular cartilage has been damaged by intra-articular injection of IA reduces chondrocyte depletion, results in an increase in pericellular Safranin-O staining around surviving chondrocytes, and prevents fibrillation of the articular surface. The data suggest that exercise protected, or facilitated recovery of, chondrocytes subjected to chemical injury, and that the surviving cells then synthesised a matrix which was sufficiently normal to withstand impulsive joint loading. On the other hand, the exercise regimen accelerated osteophyte formation, and led to formation of osteophytes in sites at which they did not develop in animals which received intra-articular IA but which were not exercised. Images Fig. 1 (cont.) Fig. 1 Fig. 2 Fig. 3 PMID:6526713

  4. Determining Tension-Compression Nonlinear Mechanical Properties of Articular Cartilage from Indentation Testing.

    PubMed

    Chen, Xingyu; Zhou, Yilu; Wang, Liyun; Santare, Michael H; Wan, Leo Q; Lu, X Lucas

    2016-04-01

    The indentation test is widely used to determine the in situ biomechanical properties of articular cartilage. The mechanical parameters estimated from the test depend on the constitutive model adopted to analyze the data. Similar to most connective tissues, the solid matrix of cartilage displays different mechanical properties under tension and compression, termed tension-compression nonlinearity (TCN). In this study, cartilage was modeled as a porous elastic material with either a conewise linear elastic matrix with cubic symmetry or a solid matrix reinforced by a continuous fiber distribution. Both models are commonly used to describe the TCN of cartilage. The roles of each mechanical property in determining the indentation response of cartilage were identified by finite element simulation. Under constant loading, the equilibrium deformation of cartilage is mainly dependent on the compressive modulus, while the initial transient creep behavior is largely regulated by the tensile stiffness. More importantly, altering the permeability does not change the shape of the indentation creep curves, but introduces a parallel shift along the horizontal direction on a logarithmic time scale. Based on these findings, a highly efficient curve-fitting algorithm was designed, which can uniquely determine the three major mechanical properties of cartilage (compressive modulus, tensile modulus, and permeability) from a single indentation test. The new technique was tested on adult bovine knee cartilage and compared with results from the classic biphasic linear elastic curve-fitting program. PMID:26240062

  5. A biphasic finite element study on the role of the articular cartilage superficial zone in confined compression.

    PubMed

    Guo, Hongqiang; Maher, Suzanne A; Torzilli, Peter A

    2015-01-01

    The aim of this study was to investigate the role of the superficial zone on the mechanical behavior of articular cartilage. Confined compression of articular cartilage was modeled using a biphasic finite element analysis to calculate the one-dimensional deformation of the extracellular matrix (ECM) and movement of the interstitial fluid through the ECM and articular surface. The articular cartilage was modeled as an inhomogeneous, nonlinear hyperelastic biphasic material with depth and strain-dependent material properties. Two loading conditions were simulated, one where the superficial zone was loaded with a porous platen (normal test) and the other where the deep zone was loaded with the porous platen (upside down test). Compressing the intact articular cartilage with 0.2 MPa stress reduced the surface permeability by 88%. Removing the superficial zone increased the rate of change for all mechanical parameters and decreased the fluid support ratio of the tissue, resulting in increased tissue deformation. Apparent permeability linearly increased after superficial removal in the normal test, yet it did not change in the upside down test. Orientation of the specimen affected the time-dependent biomechanical behavior of the articular cartilage, but not equilibrium behavior. The two tests with different specimen orientations resulted in very different apparent permeabilities, suggesting that in an experimental study which quantifies material properties of an inhomogeneous material, the specimen orientation should be stated along with the permeability result. The current study provides new insights into the role of the superficial zone on mechanical behavior of the articular cartilage. PMID:25465194

  6. Changes in permeability of rabbit articular cartilage caused by joint contracture as revealed by the peroxidase method.

    PubMed

    Nakamura, K; Ohta, N; Kawaji, W; Takata, K; Hirano, H

    1984-11-01

    Changes in permeability of adult rabbit articular cartilage caused by joint contracture were studied by light and transmission electron microscopy, employing horseradish peroxidase (HRP) as an indicator. The knee joint was plaster-immobilized for 0, 2, 4, 6, or 8 weeks in the flexion position. One ml of 4% HRP was administered in the articular cavity of the knee joint and allowed to diffuse and permeate into the articular cartilage. Distribution of the permeated HRP was visualized in the cartilage taken from the lateral condyle of the femur, utilizing the DAB-H2O2 reaction. In the normal and the non-immobilized joints, the permeated HRP reached to the matrix and chondrocytes situated in the deep layer of the articular cartilage. HRP was heavily deposited in the intercellular matrices, particularly around the chondrocytes, and was actively endocytosed by these cells. In the plaster-immobilized joints, especially after 4 weeks or longer of immobilization, the administered HRP had not permeated well and was restricted to the surface (lamina splendens) and the superficial layer of the cartilage. These results show that administered HRP diffuses into the deep layer of the articular cartilage and is actively endocytosed by chondrocytes and that the permeability of articular cartilage is remarkably reduced by joint contracture. PMID:6532371

  7. Acute and chronic response of articular cartilage to Ho:YAG laser irradiation

    NASA Astrophysics Data System (ADS)

    Trauner, Kenneth B.; Nishioka, Norman S.; Flotte, Thomas J.; Patel, Dinesh K.

    1992-06-01

    A Ho:YAG laser system operating at a wavelength of 2.1 microns has recently been introduced for use in arthroscopic surgery. The acceptability of this new tool will be determined not only by its ability to resect tissue, but also by its long term effects on articular surfaces. In order to investigate these issues further, we performed two studies to evaluate the acute and chronic effects of the laser on cartilaginous tissue. We evaluated the acute, in vitro effects of 2.1 micron laser irradiation on articular and fibrocartilage. This included the measurement of ablation efficiency, ablation threshold and thermal damage in both meniscus and articular cartilage. To document the chronic effects on articular cartilage in vivo, we next performed a ten week healing study. Eight sheep weighing 30 - 40 kg underwent bilateral arthrotomy procedures. Multiple full thickness and partial thickness defects were created. Animals were sacrificed at 0, 2, 4, and 10 weeks. The healing study demonstrated: (1) no healing of full or partial thickness defects at 10 weeks with hyaline cartilage; (2) fibrocartilaginous granulation tissue filling full thickness defects at two and four weeks, but no longer evident at ten weeks; (3) chondrocyte necrosis extending to greater than 900 microns distal to ablation craters at four weeks with no evidence of repair at later dates; and (4) chondrocyte hyperplasia at the borders of the damage zone at two weeks but no longer evident at later sacrifice dates.

  8. Effect of corticosteroids on articular cartilage: have animal studies said everything?

    PubMed

    Vandeweerd, Jean-Michel; Zhao, Yang; Nisolle, Jean-François; Zhang, Wenhui; Zhihong, Liu; Clegg, Peter; Gustin, Pascal

    2015-10-01

    Intra-articular (IA) corticosteroids (CS) have been used in the treatment of osteoarthritis for many years, although their effects on articular cartilage are not fully understood. To identify whether previous animal studies have provided enough evidence about the effects of CS, we undertook a systematic review that identified 35 relevant in vivo animal experimental studies between 1965 and 2014 assessing the effects of CS on either normal cartilage, or in either induced osteoarthritis (OA) or synovitis. The quality of the methodology was assessed. Deleterious effects, both structural and biochemical, have mainly been reported in rabbits and are associated with frequent administration of CS, sometimes at high dose and with systemic side effects. In dogs, four identified studies concluded that there were beneficial effects with methylprednisolone acetate (MPA) and triamcinolone hexacetonide therapy. In horses, MPA was mostly deleterious, while triamcinolone acetonide had positive effects in one study highly rated at quality assessment. However, many methodological weaknesses have been identified, such as the lack of pharmacokinetic and pharmocodynamics data and the large variation in doses between studies, the limited selection criteria at baseline, the absence of blinding, and the lack of statistics or appropriate controls for testing the effects of the vehicle of the drug. Those methodological weaknesses weaken the conclusions of numerous studies that assess beneficial or deleterious effects of CS on articular cartilage. Animal studies have not yet provided definitive data, and further research is required into the role of CS in articular pathobiology. PMID:26211421

  9. Highly nonlinear stress-relaxation response of articular cartilage in indentation: Importance of collagen nonlinearity.

    PubMed

    Mäkelä, J T A; Korhonen, R K

    2016-06-14

    Modern fibril-reinforced computational models of articular cartilage can include inhomogeneous tissue composition and structure, and nonlinear mechanical behavior of collagen, proteoglycans and fluid. These models can capture well experimental single step creep and stress-relaxation tests or measurements under small strains in unconfined and confined compression. Yet, it is known that in indentation, especially at high strain velocities, cartilage can express highly nonlinear response. Different fibril reinforced poroelastic and poroviscoelastic models were used to assess measured highly nonlinear stress-relaxation response of rabbit articular cartilage in indentation. Experimentally measured depth-dependent volume fractions of different tissue constituents and their mechanical nonlinearities were taken into account in the models. In particular, the collagen fibril network was modeled using eight separate models that implemented five different constitutive equations to describe the nonlinearity. These consisted of linear elastic, nonlinear viscoelastic and multiple nonlinear elastic representations. The model incorporating the most nonlinearly increasing Young׳s modulus of collagen fibrils as a function of strain captured best the experimental data. Relative difference between the model and experiment was ~3%. Surprisingly, the difference in the peak forces between the experiment and the model with viscoelastic collagen fibrils was almost 20%. Implementation of the measured volume fractions did not improve the ability of the model to capture the measured mechanical data. These results suggest that a highly nonlinear formulation for collagen fibrils is needed to replicate multi-step stress-relaxation response of rabbit articular cartilage in indentation with high strain rates. PMID:27130474

  10. The effects of hydrostatic pressure on matrix synthesis in articular cartilage

    SciTech Connect

    Hall, A.C.; Urban, J.P.; Gehl, K.A. )

    1991-01-01

    The direct effects of hydrostatic pressure on matrix synthesis in articular cartilage can be studied independently of the other factors that change during loading. We have found that the influence of hydrostatic pressure on incorporation rates of {sup 35}SO{sub 4} and ({sup 3}H)proline into adult bovine articular cartilage slices in vitro depends on the pressure level and on the time at pressure. Pressures in the physiological range (5-15 MPa) applied for 20 s or for 5 min could stimulate tracer incorporation (30-130%) during the following 2 h, but higher pressures (20-50 MPa) had no effect on incorporation rates. The degree of stimulation in cartilage obtained from different animals was found to vary; in some animals none was seen. Stimulation also varied with position along the joint. Physiological pressures (5-10 MPa) applied continuously for the 2-h incubation period also stimulated incorporation rates, but pressures greater than 20 MPa always produced a decrease that was related to the applied pressure and that was reversible. These results suggests that the hydrostatic pressure that occurs during loading is a signal that can stimulate matrix synthesis rates in articular cartilage.

  11. The Collagen Fibril Structure in the Superficial Zone of Articular Cartilage by μMRI

    PubMed Central

    Zheng, ShaoKuan; Xia, Yang

    2009-01-01

    Objective To investigate the fibril architecture of the collage matrix in the superficial zone of articular cartilage non-destructively by microscopic MRI (μMRI) T2 anisotropy. Method Six specimens of canine humeral cartilage were rotated in such a way that the normal axis of the articular surface of the cartilage specimen remained stationary and perpendicular to the static magnetic field, over a range of 180° and at a step of 15°. At each rotation angle, a quantitative T2 image was constructed at 13μm pixel resolution. Results A set of complex and depth-dependent patterns was found in the μMRI T2 anisotropy along the depth of the tissue. In the superficial zone, the T2 anisotropy is clearly periodic, which demonstrates that the distribution of the collagen fibrils in the superficial zone is not random. In the transitional zone, the periodicity of the T2 anisotropy approximately doubles with respect to that in the superficial zone. In the initial part of the radial zone, the T2 anisotropy is also periodic but inverse to that in the superficial zone. In the deep part of the radial zone, the T2 anisotropy becomes increasingly weaker and eventually disappears. Conclusion There exists a certain degree of collagen anisotropy in all zones of articular cartilage. The anisotropic imaging data can be interpreted with the aid of a collagen architecture model. PMID:19527808

  12. Hierarchical Structure of Articular Bone-Cartilage Interface and Its Potential Application for Osteochondral Tissue Engineering

    NASA Astrophysics Data System (ADS)

    Bian, Weiguo; Qin, Lian; Li, Dichen; Wang, Jin; Jin, Zhongmin

    2010-09-01

    The artificial biodegradable osteochondral construct is one of mostly promising lifetime substitute in the joint replacement. And the complex hierarchical structure of natural joint is important in developing the osteochondral construct. However, the architecture features of the interface between cartilage and bone, in particular those at the micro-and nano-structural level, remain poorly understood. This paper investigates these structural data of the cartilage-bone interface by micro computerized tomography (μCT) and Scanning Electron Microscope (SEM). The result of μCT shows that important bone parameters and the density of articular cartilage are all related to the position in the hierarchical structure. The conjunctions of bone and cartilage were defined by SEM. All of the study results would be useful for the design of osteochondral construct further manufactured by nano-tech. A three-dimensional model with gradient porous structure is constructed in the environment of Pro/ENGINEERING software.

  13. A Novel Model for the Mass Transfer of Articular Cartilage: Rolling Depression Load Device

    NASA Astrophysics Data System (ADS)

    Fan, Zhenmin; Zhang, Chunqiu; Liu, Haiying; Xu, Baoshan; Li, Jiang; Gao, Lilan

    The mass transfer is one of important aspects to maintain the physiological activity proper of tissue, specially, cartilage cannot run without mechanical environment. The mechanical condition drives nutrition in and waste out in the cartilage tissue, the change of this process plays a key role for biological activity. Researchers used to adopt compression to study the mass transfer in cartilage, here we firstly establish a new rolling depression load (RDL) device, and also put this device into practice. The device divided into rolling control system and the compression adjusting mechanism. The rolling control system makes sure the pure rolling and uniform speed of roller applying towards cultured tissue. The compression adjusting mechanism can realize different compressive magnitudes and uniform compression. Preliminary test showed that rolling depression load indeed enhances the process of mass transfer articular cartilage.

  14. Chondroprotective Effect of Kartogenin on CD44-Mediated Functions in Articular Cartilage and Chondrocytes

    PubMed Central

    Ono, Yohei; Ishizuka, Shinya; Knudson, Cheryl B.

    2014-01-01

    Objective: A recent report identified the small molecule kartogenin as a chondrogenic and chondroprotective agent. Since changes in hyaluronan metabolism occur during cartilage degeneration in osteoarthritis, we began studies to determine whether there was a connection between extracellular hyaluronan, CD44–hyaluronan interactions and the effects of kartogenin on articular chondrocytes. Methods: Chondrocytes cultured in monolayers, bioengineered neocartilages, or cartilage explants were treated with kartogenin with or without stimulation by IL-1β. Accumulation of matrix was visualized by a particle exclusion assay or by safranin O staining and release of sulfated glycosaminoglycans was determined. Production of aggrecanases and aggrecan G1-ITEGE neoepitope, fragmentation of CD44 and the SMAD1/5/8 signaling pathway were evaluated by western blotting. Results: Kartogenin treatment enhanced chondrocyte pericellular matrix assembly and retention in the presence of IL-1β. The chondroprotective effects of kartogenin on IL-1β-induced release of sulfated glycosaminoglycans from articular cartilage explants, reduction in safranin O staining of neocartilage discs as well as a reduction in aggrecan G1-ITEGE neoepitope in chondrocyte and explant cartilage cultures were observed. Kartogenin partially blocked the IL-1β-induced increased expression of ADAMTS-5. Additionally, kartogenin-treated articular chondrocytes exhibited a decrease in CD44 proteolytic fragmentation. However, kartogenin treatment did not enhance proteoglycan in control, non-IL-1β-treated cultures. Similarly, kartogenin enhanced the SMAD1 phosphorylation but only following pretreatment with IL-1β. Conclusion: These studies provide novel information on the chondroprotective function of kartogenin in adult articular cartilage. The effects of kartogenin are significant after activation of chondrocytic chondrolysis, which may occur following disruption of homeostasis maintained by hyaluronan–CD44

  15. Freeze-thaw treatment effects on the dynamic mechanical properties of articular cartilage

    PubMed Central

    2010-01-01

    Background As a relatively non-regenerative tissue, articular cartilage has been targeted for cryopreservation as a method of mitigating a lack of donor tissue availability for transplant surgeries. In addition, subzero storage of articular cartilage has long been used in biomedical studies using various storage temperatures. The current investigation studies the potential for freeze-thaw to affect the mechanical properties of articular cartilage through direct comparison of various subzero storage temperatures. Methods Both subzero storage temperature as well as freezing rate were compared using control samples (4°C) and samples stored at either -20°C or -80°C as well as samples first snap frozen in liquid nitrogen (-196°C) prior to storage at -80°C. All samples were thawed at 37.5°C to testing temperature (22°C). Complex stiffness and hysteresis characterized load resistance and damping properties using a non-destructive, low force magnitude, dynamic indentation protocol spanning a broad loading rate range to identify the dynamic viscoelastic properties of cartilage. Results Stiffness levels remained unchanged with exposure to the various subzero temperatures. Hysteresis increased in samples snap frozen at -196°C and stored at -80°C, though remained unchanged with exposure to the other storage temperatures. Conclusions Mechanical changes shown are likely due to ice lens creation, where frost heave effects may have caused collagen damage. That storage to -20°C and -80°C did not alter the mechanical properties of articular cartilage shows that when combined with a rapid thawing protocol to 37.5°C, the tissue may successfully be stored at subzero temperatures. PMID:20932309

  16. Microstructural Remodeling of Articular Cartilage Following Defect Repair by Osteochondral Autograft Transfer

    PubMed Central

    Raub, CB; Hsu, SC; Chan, EF; Shirazi, R; Chen, AC; Chnari, E; Semler, EJ; Sah, RL

    2013-01-01

    Objective To assess collagen network alterations occurring with flow and other abnormalities of articular cartilage at medial femoral condyle (MFC) sites repaired with osteochondral autograft (OATS) after 6 and 12 months, using quantitative polarized light microscopy (qPLM) and other histopathological methods Design The collagen network structure of articular cartilage of OATS-repaired defects and non-operated contralateral control sites were compared by qPLM analysis of parallelism index (PI), orientation angle (α) relative to the local tissue axes, and retardance (Γ) as a function of depth. qPLM parameter maps were also compared to ICRS and Modified O’Driscoll grades, and cell and matrix sub-scores, for sections stained with H&E and Safranin-O, and for Collagen-I and II Results Relative to non-operated normal cartilage, OATS-repaired regions exhibited structural deterioration, with low PI and more horizontal α, and unique structural alteration in adjacent host cartilage: more aligned superficial zone, and reoriented deep zone lateral to the graft, and matrix disorganization in cartilage overhanging the graft. Shifts in α and PI from normal site-specific values were correlated with histochemical abnormalities and co-localized with changes in cell organization/orientation, cloning, or loss, indicative of cartilage flow, remodeling, and deterioration, respectively Conclusions qPLM reveals a number of unique localized alterations of the collagen network in both adjacent host and implanted cartilage in OATS-repaired defects, associated with abnormal chondrocyte organization. These alterations are consistent with mechanobiological processes and the direction and magnitude of cartilage strain. PMID:23528954

  17. A new method for evaluating the degeneration of articular cartilage using pulse-echo ultrasound

    NASA Astrophysics Data System (ADS)

    Sun, Anyu; Bai, Xiaolong; Ju, Bing-Feng

    2015-03-01

    This paper presents a novel nondestructive ultrasonic technique for measuring the sound speed and acoustic impedance of articular cartilage using the pulsed V(z,t) technique. V(z,t) data include a series of pulsed ultrasonic echoes collected using different distances between the ultrasonic transducer and the specimen. The 2D Fourier transform is applied to the V(z,t) data to reconstruct the 2D reflection spectrum R(θ,ω). To obtain the reflection coefficient of articular cartilage, the V(z,t) data from a reference specimen with a well-known reflection coefficient are obtained to eliminate the dependence on the general system transfer function. The ultrasound-derived aggregate modulus (Ha) is computed based on the measured reflection coefficient and the sound speed. In the experiment, 32 cartilage-bone samples were prepared from bovine articular cartilage, and 16 samples were digested using 0.25% trypsin solution. The sound speed and Ha of these cartilage samples were evaluated before and after degeneration. The magnitude of the sound speed decreased with trypsin digestion (from 1663 ± 5.6 m/s to 1613 ± 5.3 m/s). Moreover, the Young's modulus in the corresponding degenerative state was measured and was correlated with the ultrasound-derived aggregate modulus. The ultrasound-derived aggregate modulus was determined to be highly correlated with the Young's modulus (n = 16, r>0.895, p<0.003, Pearson correlation test for each measurement). The results demonstrate the effectiveness of using the proposed method to assess the changes in sound speed and the ultrasound-derived aggregate modulus of cartilage after degeneration.

  18. Wear and damage of articular cartilage with friction against orthopedic implant materials.

    PubMed

    Oungoulian, Sevan R; Durney, Krista M; Jones, Brian K; Ahmad, Christopher S; Hung, Clark T; Ateshian, Gerard A

    2015-07-16

    The objective of this study was to measure the wear response of immature bovine articular cartilage tested against glass or alloys used in hemiarthroplasties. Two cobalt chromium alloys and a stainless steel alloy were selected for these investigations. The surface roughness of one of the cobalt chromium alloys was also varied within the range considered acceptable by regulatory agencies. Cartilage disks were tested in a configuration that promoted loss of interstitial fluid pressurization to accelerate conditions believed to occur in hemiarthroplasties. Results showed that considerably more damage occurred in cartilage samples tested against stainless steel (10 nm roughness) and low carbon cobalt chromium alloy (27 nm roughness) compared to glass (10 nm) and smoother low or high carbon cobalt chromium (10 nm). The two materials producing the greatest damage also exhibited higher equilibrium friction coefficients. Cartilage damage occurred primarily in the form of delamination at the interface between the superficial tangential zone and the transitional middle zone, with much less evidence of abrasive wear at the articular surface. These results suggest that cartilage damage from frictional loading occurs as a result of subsurface fatigue failure leading to the delamination. Surface chemistry and surface roughness of implant materials can have a significant influence on tissue damage, even when using materials and roughness values that satisfy regulatory requirements. PMID:25912663

  19. Wear and Damage of Articular Cartilage with Friction Against Orthopaedic Implant Materials

    PubMed Central

    Oungoulian, Sevan R.; Durney, Krista M.; Jones, Brian K.; Ahmad, Christopher S.; Hung, Clark T.; Ateshian, Gerard A.

    2015-01-01

    The objective of this study was to measure the wear response of immature bovine articular cartilage tested against glass or alloys used in hemiarthroplasties. Two cobalt chromium alloys and a stainless steel alloy were selected for these investigations. The surface roughness of one of the cobalt chromium alloys was also varied within the range considered acceptable by regulatory agencies. Cartilage disks were tested in a configuration that promoted loss of interstitial fluid pressurization to accelerate conditions believed to occur in hemiarthroplasties. Results showed that considerably more damage occurred in cartilage samples tested against stainless steel (10 nm roughness) and low carbon cobalt chromium alloy (27 nm roughness) compared to glass (10 nm) and smoother low or high carbon cobalt chromium (10 nm). The two materials producing the greatest damage also exhibited higher equilibrium friction coefficients. Cartilage damage occurred primarily in the form of delamination at the interface between the superficial tangential zone and the transitional middle zone, with much less evidence of abrasive wear at the articular surface. These results suggest that cartilage damage from frictional loading occurs as a result of subsurface fatigue failure leading to the delamination. Surface chemistry and surface roughness of implant materials can have a significant influence on tissue damage, even when using materials and roughness values that satisfy regulatory requirements. PMID:25912663

  20. Biomechanical properties of third carpal articular cartilage in exercised and nonexercised horses.

    PubMed

    Palmer, J L; Bertone, A L; Mansour, J; Carter, B G; Malemud, C J

    1995-11-01

    The relevance of site and exercise on the biomechanical properties of the articular cartilage from the equine third carpal bone were assessed by creep indentation testing. Six horses were exercised for 30 minutes three times weekly. Another six horses were housed in box stalls and were not exercised. At the conclusion of the study, one third carpal bone from each horse was harvested and the KLM biphasic material properties of cartilage were determined at 12 sites. There was a significant (p < 0.01) effect of site but not exercise on the cartilage aggregate modulus, which was significantly lower for sites on the dorsal aspect of the radial facet and for all sites on the intermediate facet as compared with sites on the palmar aspect of the radial facet of the third carpal bone. Exercise significantly increased the permeability constant at all sites when compared with the nonexercised group, but there was no difference between sites within groups. Exercise also significantly increased Poisson's ratio, but only at sites located on the palmar aspect of the radial facet. In general, both site and exercise influence the biomechanical behavior of third carpal articular cartilage. Inherent differences in cartilage biomechanical properties within a joint correlate with the location specificity of cartilaginous lesions in the equine midcarpal joint. PMID:8544021

  1. Major biological obstacles for persistent cell-based regeneration of articular cartilage

    PubMed Central

    Steinert, Andre F; Ghivizzani, Steven C; Rethwilm, Axel; Tuan, Rocky S; Evans, Christopher H; Nöth, Ulrich

    2007-01-01

    Hyaline articular cartilage, the load-bearing tissue of the joint, has very limited repair and regeneration capacities. The lack of efficient treatment modalities for large chondral defects has motivated attempts to engineer cartilage constructs in vitro by combining cells, scaffold materials and environmental factors, including growth factors, signaling molecules, and physical influences. Despite promising experimental approaches, however, none of the current cartilage repair strategies has generated long lasting hyaline cartilage replacement tissue that meets the functional demands placed upon this tissue in vivo. The reasons for this are diverse and can ultimately result in matrix degradation, differentiation or integration insufficiencies, or loss of the transplanted cells and tissues. This article aims to systematically review the different causes that lead to these impairments, including the lack of appropriate differentiation factors, hypertrophy, senescence, apoptosis, necrosis, inflammation, and mechanical stress. The current conceptual basis of the major biological obstacles for persistent cell-based regeneration of articular cartilage is discussed, as well as future trends to overcome these limitations. PMID:17561986

  2. The collagen structure of equine articular cartilage, characterized using polarization-sensitive optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Ugryumova, Nadya; Attenburrow, Don P.; Winlove, C. Peter; Matcher, Stephen J.

    2005-08-01

    Optical coherence tomography and polarization-sensitive optical coherence tomography images of equine articular cartilage are presented. Measurements were made on intact joint surfaces. Significant (e.g. × 2) variations in the intrinsic birefringence were found over spatial scales of a few millimetres, even on samples taken from young (18 month) animals that appeared visually homogeneous. A comparison of data obtained on a control tissue (equine flexor tendon) further suggests that significant variations in the orientation of the collagen fibres relative to the plane of the joint surface exist. Images of visually damaged cartilage tissue show characteristic features both in terms of the distribution of optical scatterers and of the birefringent components.

  3. Chondrogenic Differentiation of Human Adipose-Derived Stem Cells: A New Path in Articular Cartilage Defect Management?

    PubMed Central

    Stromps, Jan-Philipp; Paul, Nora Emilie; Rath, Björn; Nourbakhsh, Mahtab; Bernhagen, Jürgen; Pallua, Norbert

    2014-01-01

    According to data published by the Centers for Disease Control and Prevention, over 6 million people undergo a variety of medical procedures for the repair of articular cartilage defects in the U.S. each year. Trauma, tumor, and age-related degeneration can cause major defects in articular cartilage, which has a poor intrinsic capacity for healing. Therefore, there is substantial interest in the development of novel cartilage tissue engineering strategies to restore articular cartilage defects to a normal or prediseased state. Special attention has been paid to the expansion of chondrocytes, which produce and maintain the cartilaginous matrix in healthy cartilage. This review summarizes the current efforts to generate chondrocytes from adipose-derived stem cells (ASCs) and provides an outlook on promising future strategies. PMID:25019085

  4. Repair of articular cartilage and meniscal tears by photoactive dyes: in-vivo study

    NASA Astrophysics Data System (ADS)

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

    1996-12-01

    We describe healing results of our 6 month study of a repair procedure which evokes the healing response in meniscal tears and partial thickness defects in articular cartilage by a non-thermal tissue sparing photochemical weld using 1,8-naphthalimide dyes. Welds of incisional flaps in adult sheep meniscus and femoral articular cartilage were made using the dye MBM Gold 012011012 at 12 mM in PBS, 457.9nm Argon ion laser radiation at 800 mW/cm2, 7.5 minutes with approximately 1 kg/cm2 externally applied pressure. Gross appearance of tissues in all welded knees appeared normal. Hematoxylin and eosin stained sections disclosed close bonding of welded areas and continuing healing response as cellular recruitment.

  5. Mitochondrial Electron Transport and Glycolysis are coupled in Articular Cartilage

    PubMed Central

    Martin, James A.; Martini, Anne; Molinari, Alexander; Morgan, Walter; Ramalingam, Wendy; Buckwalter, Joseph A.; McKinley, Todd O.

    2012-01-01

    Objective Although the majority of the ATP in chondrocytes is made by glycolysis rather than by oxidative phosphorylation in mitochondria there is evidence to suggest that reactive oxygen species produced by mitochondrial electron transport help to maintain cellular redox balance in favor of glycolysis. The objective of this study was to test this hypothesis by determining if rotenone, which inhibits electron transport and blocks oxidant production inhibits glycolytic ATP synthesis. Design Bovine osteochondral explants were treated with rotenone, an electron transport inhibitor; or oligomycin an ATP synthase inhibitor; or 2-fluoro-2-deoxy-D-glucose, a glycolysis inhibiter; or peroxide, an exogenous oxidant; or mitoquinone, a mitochondria-targeted anti-oxidant. Cartilage extracts were assayed for ATP, NAD+, and NADH, and culture medium was assayed for pyruvate and lactate after 24 hours of treatment. Imaging studies were used to measure superoxide production in cartilage. Results Rotenone and 2-fluoro-2-deoxy-D-glucose caused a significant decline in cartilage ATP (p < 0.001). In contrast, ATP levels were not affected by oligomycin. Peroxide treatment blocked rotenone effects on ATP, while treatment with MitoQ significantly suppressed ATP levels. Rotenone and 2-fluoro-2-deoxy-D-glucose caused a significant decline in pyruvate, but not in lactate production. NADH:NAD+ ratios decreased significantly in both rotenone and 2-fluoro-2-deoxy-D-glucose-treated explants (p < 0.05). Rotenone also significantly reduced superoxide production Conclusions These findings showing a link between glycolysis and electron transport are consistent with previous reports on the critical need for oxidants to support normal chondrocyte metabolism. They suggest a novel role for mitochondria in cartilage homeostasis that is independent of oxidative phosphorylation. PMID:22305999

  6. On the functional organisation of hyaline articular cartilage.

    PubMed

    Pieper, K S; Fehrmann, P; Vergani, G; Herrmann, M

    1995-01-01

    Function of agonists and antagonists and the centering effect of the muscles on the connected joint result in constant changes of the site of load. Based on a model it is assumed that chondric cells organise in form of "functional units" within the single layers of the hyaline tectorial cartilage. In each case a small number of those units is subject to the rhythm of load and relief in a fixed period of time given. After 24-hour-culture of small pieces of cartilage in Ham's F-10 medium erected cilia are found on the predominantly ciliated chondrocytes with this indicating relief of pressure. In these cells massive glycogen synthesis and an active Golgi apparatus are present. In parallel, chondrones are found in which cellular contact functions via a cilium. Time-dependent glycogen occurs in these cells too. Cells having almost the same synthesis time course of the glycogen join up to form "functional units", which are particularly involved in the biomechanic cartilage behavior in the radiar cell zone. PMID:11322284

  7. High Density Infill in Cracks and Protrusions from the Articular Calcified Cartilage in Osteoarthritis in Standardbred Horse Carpal Bones

    PubMed Central

    Laverty, Sheila; Lacourt, Mathieu; Gao, Chan; Henderson, Janet E.; Boyde, Alan

    2015-01-01

    We studied changes in articular calcified cartilage (ACC) and subchondral bone (SCB) in the third carpal bones (C3) of Standardbred racehorses with naturally-occurring repetitive loading-induced osteoarthritis (OA). Two osteochondral cores were harvested from dorsal sites from each of 15 post-mortem C3 and classified as control or as showing early or advanced OA changes from visual inspection. We re-examined X-ray micro-computed tomography (µCT) image sets for the presence of high-density mineral infill (HDMI) in ACC cracks and possible high-density mineralized protrusions (HDMP) from the ACC mineralizing (tidemark) front (MF) into hyaline articular cartilage (HAC). We hypothesized and we show that 20-µm µCT resolution in 10-mm diameter samples is sufficient to detect HDMI and HDMP: these are lost upon tissue decalcification for routine paraffin wax histology owing to their predominant mineral content. The findings show that µCT is sufficient to discover HDMI and HDMP, which were seen in 2/10 controls, 6/9 early OA and 8/10 advanced OA cases. This is the first report of HDMI and HDMP in the equine carpus and in the Standardbred breed and the first to rely solely on µCT. HDMP are a candidate cause for mechanical tissue destruction in OA. PMID:25927581

  8. High density infill in cracks and protrusions from the articular calcified cartilage in osteoarthritis in standardbred horse carpal bones.

    PubMed

    Laverty, Sheila; Lacourt, Mathieu; Gao, Chan; Henderson, Janet E; Boyde, Alan

    2015-01-01

    We studied changes in articular calcified cartilage (ACC) and subchondral bone (SCB) in the third carpal bones (C3) of Standardbred racehorses with naturally-occurring repetitive loading-induced osteoarthritis (OA). Two osteochondral cores were harvested from dorsal sites from each of 15 post-mortem C3 and classified as control or as showing early or advanced OA changes from visual inspection. We re-examined X-ray micro-computed tomography (µCT) image sets for the presence of high-density mineral infill (HDMI) in ACC cracks and possible high-density mineralized protrusions (HDMP) from the ACC mineralizing (tidemark) front (MF) into hyaline articular cartilage (HAC). We hypothesized and we show that 20-µm µCT resolution in 10-mm diameter samples is sufficient to detect HDMI and HDMP: these are lost upon tissue decalcification for routine paraffin wax histology owing to their predominant mineral content. The findings show that µCT is sufficient to discover HDMI and HDMP, which were seen in 2/10 controls, 6/9 early OA and 8/10 advanced OA cases. This is the first report of HDMI and HDMP in the equine carpus and in the Standardbred breed and the first to rely solely on µCT. HDMP are a candidate cause for mechanical tissue destruction in OA. PMID:25927581

  9. Deletion of IFT80 Impairs Epiphyseal and Articular Cartilage Formation Due to Disruption of Chondrocyte Differentiation

    PubMed Central

    Yuan, Xue; Yang, Shuying

    2015-01-01

    Intraflagellar transport proteins (IFT) play important roles in cilia formation and organ development. Partial loss of IFT80 function leads Jeune asphyxiating thoracic dystrophy (JATD) or short-rib polydactyly (SRP) syndrome type III, displaying narrow thoracic cavity and multiple cartilage anomalies. However, it is unknown how IFT80 regulates cartilage formation. To define the role and mechanism of IFT80 in chondrocyte function and cartilage formation, we generated a Col2α1; IFT80f/f mouse model by crossing IFT80f/f mice with inducible Col2α1-CreER mice, and deleted IFT80 in chondrocyte lineage by injection of tamoxifen into the mice in embryonic or postnatal stage. Loss of IFT80 in the embryonic stage resulted in short limbs at birth. Histological studies showed that IFT80-deficient mice have shortened cartilage with marked changes in cellular morphology and organization in the resting, proliferative, pre-hypertrophic, and hypertrophic zones. Moreover, deletion of IFT80 in the postnatal stage led to mouse stunted growth with shortened growth plate but thickened articular cartilage. Defects of ciliogenesis were found in the cartilage of IFT80-deficient mice and primary IFT80-deficient chondrocytes. Further study showed that chondrogenic differentiation was significantly inhibited in IFT80-deficient mice due to reduced hedgehog (Hh) signaling and increased Wnt signaling activities. These findings demonstrate that loss of IFT80 blocks chondrocyte differentiation by disruption of ciliogenesis and alteration of Hh and Wnt signaling transduction, which in turn alters epiphyseal and articular cartilage formation. PMID:26098911

  10. Fractional calculus model of articular cartilage based on experimental stress-relaxation

    NASA Astrophysics Data System (ADS)

    Smyth, P. A.; Green, I.

    2015-05-01

    Articular cartilage is a unique substance that protects joints from damage and wear. Many decades of research have led to detailed biphasic and triphasic models for the intricate structure and behavior of cartilage. However, the models contain many assumptions on boundary conditions, permeability, viscosity, model size, loading, etc., that complicate the description of cartilage. For impact studies or biomimetic applications, cartilage can be studied phenomenologically to reduce modeling complexity. This work reports experimental results on the stress-relaxation of equine articular cartilage in unconfined loading. The response is described by a fractional calculus viscoelastic model, which gives storage and loss moduli as functions of frequency, rendering multiple advantages: (1) the fractional calculus model is robust, meaning that fewer constants are needed to accurately capture a wide spectrum of viscoelastic behavior compared to other viscoelastic models (e.g., Prony series), (2) in the special case where the fractional derivative is 1/2, it is shown that there is a straightforward time-domain representation, (3) the eigenvalue problem is simplified in subsequent dynamic studies, and (4) cartilage stress-relaxation can be described with as few as three constants, giving an advantage for large-scale dynamic studies that account for joint motion or impact. Moreover, the resulting storage and loss moduli can quantify healthy, damaged, or cultured cartilage, as well as artificial joints. The proposed characterization is suited for high-level analysis of multiphase materials, where the separate contribution of each phase is not desired. Potential uses of this analysis include biomimetic dampers and bearings, or artificial joints where the effective stiffness and damping are fundamental parameters.