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Sample records for managing articular cartilage

  1. Articular cartilage biochemistry

    SciTech Connect

    Kuettner, K.E.; Schleyerbach, R.; Hascall, V.C.

    1986-01-01

    This book contains six parts, each consisting of several papers. The part titles are: Cartilage Matrix Components; Biosynthesis and Characterization of Cartilage--Specific Matrix Components and Events; Cartilage Metabolism; In Vitro Studies of Articular Cartilage Metabolism; Normal and Pathologic Metabolism of Cartilage; and Destruction of the Articular Cartilage in Rheumatoid Diseases. Some of the paper topics are: magnetic resonance imaging; joint destruction; age-related changes; proteoglycan structure; and biosynthesis of cartilage proteoglycan.

  2. Articular Cartilage Injury in Athletes

    PubMed Central

    McAdams, Timothy R.; Mithoefer, Kai; Scopp, Jason M.; Mandelbaum, Bert R.

    2010-01-01

    Articular cartilage lesions in the athletic population are observed with increasing frequency and, due to limited intrinsic healing capacity, can lead to progressive pain and functional limitation over time. If left untreated, isolated cartilage lesions can lead to progressive chondropenia or global cartilage loss over time. A chondropenia curve is described to help predict the outcome of cartilage injury based on different lesion and patient characteristics. Nutriceuticals and chondroprotective agents are being investigated as tools to slow the development of chondropenia. Several operative techniques have been described for articular cartilage repair or replacement and, more recently, cartilage regeneration. Rehabilitation guidelines are being developed to meet the needs of these new techniques. Next-generation techniques are currently evaluated to optimize articular cartilage repair biology and to provide a repair cartilage tissue that can withstand the high mechanical loads experienced by the athlete with consistent long-term durability. PMID:26069548

  3. 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

  4. Lubrication of Articular Cartilage.

    PubMed

    Jahn, Sabrina; Seror, Jasmine; Klein, Jacob

    2016-07-11

    The major synovial joints such as hips and knees are uniquely efficient tribological systems, able to articulate over a wide range of shear rates with a friction coefficient between the sliding cartilage surfaces as low as 0.001 up to pressures of more than 100 atm. No human-made material can match this. The means by which such surfaces maintain their very low friction has been intensively studied for decades and has been attributed to fluid-film and boundary lubrication. Here, we focus especially on the latter: the reduction of friction by molecular layers at the sliding cartilage surfaces. In particular, we discuss such lubrication in the light of very recent advances in our understanding of boundary effects in aqueous media based on the paradigms of hydration lubrication and of the synergism between different molecular components of the synovial joints (namely hyaluronan, lubricin, and phospholipids) in enabling this lubrication.

  5. Evaluation of the Quality, Accuracy, and Readability of Online Patient Resources for the Management of Articular Cartilage Defects.

    PubMed

    Wang, Dean; Jayakar, Rohit G; Leong, Natalie L; Leathers, Michael P; Williams, Riley J; Jones, Kristofer J

    2017-04-01

    Objective Patients commonly use the Internet to obtain their health-related information. The purpose of this study was to investigate the quality, accuracy, and readability of online patient resources for the management of articular cartilage defects. Design Three search terms ("cartilage defect," "cartilage damage," "cartilage injury") were entered into 3 Internet search engines (Google, Bing, Yahoo). The first 25 websites from each search were collected and reviewed. The quality and accuracy of online information were independently evaluated by 3 reviewers using predetermined scoring criteria. The readability was evaluated using the Flesch-Kincaid (FK) grade score. Results Fifty-three unique websites were evaluated. Quality ratings were significantly higher in websites with a FK score >11 compared to those with a score of ≤11 ( P = 0.021). Only 10 websites (19%) differentiated between focal cartilage defects and diffuse osteoarthritis. Of these, 7 (70%) were elicited using the search term "cartilage defect" ( P = 0.038). The average accuracy of the websites was high (11.7 out of maximum 12), and the average FK grade level (13.4) was several grades higher than the recommended level for readable patient education material (eighth grade level). Conclusions The quality and readability of online patient resources for articular cartilage defects favor those with a higher level of education. Additionally, the majority of these websites do not distinguish between focal chondral defects and diffuse osteoarthritis, which can fail to provide appropriate patient education and guidance for available treatment. Clinicians should help guide patients toward high-quality, accurate, and readable online patient education material.

  6. Recent Advances in MRI of Articular Cartilage

    PubMed Central

    Gold, Garry E.; Chen, Christina A.; Koo, Seungbum; Hargreaves, Brian A.; Bangerter, Neal K.

    2010-01-01

    OBJECTIVE MRI is the most accurate noninvasive method available to diagnose disorders of articular cartilage. Conventional 2D and 3D approaches show changes in cartilage morphology. Faster 3D imaging methods with isotropic resolution can be reformatted into arbitrary planes for improved detection and visualization of pathology. Unique contrast mechanisms allow us to probe cartilage physiology and detect changes in cartilage macromolecules. CONCLUSION MRI has great promise as a noninvasive comprehensive tool for cartilage evaluation. PMID:19696274

  7. 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

  8. [The effects of exercise on articular cartilage].

    PubMed

    Ozkan, Cenk; Sarpel, Yaman; Biçer, O Sunkar

    2007-01-01

    The effect of exercise on articular cartilage has been assessed on animal models and on humans using various imaging techniques. Joint cartilage, whose water content decreases itself thanks to its unique permeable medium, maintains load distribution and joint function together with the synovial fluid under physiologic conditions and sports activities. The adaptive capacity of joint cartilage is limited under various conditions such as excessive load bearing or prolonged immobilization; however, when these factors are reversed deformed cartilage returns to its former state under normal conditions. Due to its adverse effect on joint cartilage, immobilization period following cartilage damage or operation should be as short as possible for wound healing. It is reported that exercise contributes to cartilage healing and reduces risk for injury, and that moderate exercise can even decrease the number of cases requiring arthroplasty. Conversely, excessive (harsh) exercise may be associated with increased cartilage damage or degenerative changes. Despite the presence of osteophytic changes in joint cartilage of athletes performing mild sports activities, these may not result in osteoarthritis due to the adaptive feature of joint cartilage. In contrast, the risk for osteoarthritis is increased in professional sportsmen exposed to acute repetitive impact and torsional loading. This article reviews the influence of controlled, passive-active exercise on healing, and on the development of osteoarthritis and the short- and long-term changes in articular cartilage associated with exercise and participation in sports of different duration and intensity.

  9. Locating articular cartilage in MR images

    NASA Astrophysics Data System (ADS)

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

    2005-04-01

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

  10. A peek into the possible future of management of articular cartilage injuries: gene therapy and scaffolds for cartilage repair.

    PubMed

    Kim, Hubert T; Zaffagnini, Stefano; Mizuno, Shuichi; Abelow, Stephen; Safran, Marc R

    2006-10-01

    Two rapidly progressing areas of research will likely contribute to cartilage repair procedures in the foreseeable future: gene therapy and synthetic scaffolds. Gene therapy refers to the transfer of new genetic information to cells that contribute to the cartilage repair process. This approach allows for manipulation of cartilage repair at the cellular and molecular level. Scaffolds are the core technology for the next generation of autologous cartilage implantation procedures in which synthetic matrices are used in conjunction with chondrocytes. This approach can be improved further using bioreactor technologies to enhance the production of extracellular matrix proteins by chondrocytes seeded onto a scaffold. The resulting "neo-cartilage implant" matures within the bioreactor, and can then be used to fill cartilage defects.

  11. 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

  12. Preparation of Articular Cartilage Specimens for Scanning Electron Microscopy.

    PubMed

    Stupina, T A

    2016-08-01

    We developed and adapted a technology for preparation of articular cartilage specimens for scanning electron microscopy. The method includes prefixation processing, fixation, washing, and dehydration of articular cartilage specimens with subsequent treatment in camphene and air-drying. The technological result consists in prevention of deformation of the articular cartilage structures. The method is simpler and cheaper than the known technologies.

  13. 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

  14. [Biogenic stimulants of metabolism in articular cartilage].

    PubMed

    Novikov, V E; Novikova, A V

    2011-01-01

    The review considers issues of pharmacodynamics and clinical applications of drugs with the metabolic type of action, which stimulate regeneration and provide the protective action on articular cartilage in cases of osteoarthritis. Published data of the experimental and clinical trials of the main chondroprotective agents are analyzed.

  15. Anisotropic hydraulic permeability in compressed articular cartilage.

    PubMed

    Reynaud, Boris; Quinn, Thomas M

    2006-01-01

    The extent to which articular cartilage hydraulic permeability is anisotropic is largely unknown, despite its importance for understanding mechanisms of joint lubrication, load bearing, transport phenomena, and mechanotransduction. We developed and applied new techniques for the direct measurement of hydraulic permeability within statically compressed adult bovine cartilage explant disks, dissected such that disk axes were perpendicular to the articular surface. Applied pressure gradients were kept small to minimize flow-induced matrix compaction, and fluid outflows were measured by observation of a meniscus in a glass capillary under a microscope. Explant disk geometry under radially unconfined axial compression was measured by direct microscopic observation. Pressure, flow, and geometry data were input to a finite element model where hydraulic permeabilities in the disk axial and radial directions were determined. At less than 10% static compression, near free-swelling conditions, hydraulic permeability was nearly isotropic, with values corresponding to those of previous studies. With increasing static compression, hydraulic permeability decreased, but the radially directed permeability decreased more dramatically than the axially directed permeability such that strong anisotropy (a 10-fold difference between axial and radial directions) in the hydraulic permeability tensor was evident for static compression of 20-40%. Results correspond well with predictions of a previous microstructurally-based model for effects of tissue mechanical deformations on glycosaminoglycan architecture and cartilage hydraulic permeability. Findings inform understanding of structure-function relationships in cartilage matrix, and suggest several biomechanical roles for compression-induced anisotropic hydraulic permeability in articular cartilage.

  16. Development of an artificial articular cartilage.

    PubMed

    Oka, M; Noguchi, T; Kumar, P; Ikeuchi, K; Yamamuro, T; Hyon, S H; Ikada, Y

    1990-01-01

    We have attempted to develop an artificial articular cartilage on the basis of a new viewpoint of joint biomechanics in which lubrication and load-bearing mechanisms of natural and artificial joints are compared. We investigated poly(vinyl alcohol)-hydrogel (PVA-H) which has been recognized as a rubber-like gel and have improved the mechanical properties of this gel through a new synthetic process. In this article we report the biocompatibility and various mechanical properties of the new, improved PVA-H from the aspect of its usefulness as artificial articular cartilage. As regards the lubrication, we measured the change of thickness and fluid pressure of the gap formed between a glass plate and the specimen under loading and found that the PVA-H had a thicker fluid film under higher pressure than polyethylene (PE). 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 as large as that of PE. Histological findings of the articular cartilage and synovial membranes around the PVA-H implanted for 8-52 weeks showed neither inflammatory nor degenerative changes. The PVA-H artificial articular cartilage could be attached to the underlying bone using an osteochondral composite material. Although there remain still some problems to solve, PVA-H seems to be a very interesting and promising material which meets the requirements of artificial articular cartilage.

  17. The Effect of Intra-articular Corticosteroids on Articular Cartilage

    PubMed Central

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

    2015-01-01

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

  18. [Articular cartilage regeneration using stem cells].

    PubMed

    Kanamoto, Takashi; Nakamura, Norimasa; Nakata, Ken; Yoshikawa, Hideki

    2008-12-01

    Articular cartilage plays pivotal roles in securing smooth joint kinematics and act as a shock absorber, however, it has minimal healing potential. Chondral injury could lead to the development of osteoarthritis (OA) and therefore is a major clinical concern. There have been marrow stimulating technique and osteochondral transplantation explored to promote cartilage repair. In addition, autologous chondrocyte implantation (ACI) has been developed by Peterson and Brittberg and more than 20,000 cases underwent the procedure all over the world. Recent progress in stem cell research has raised the potential application of stem cell therapy to cartilage repair. In this review, potential application of bone marrow or synovial-derived mesenchymal cells to promote cartilage repair would be discussed.

  19. 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.

  20. 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

  1. Knee Articular Cartilage Repair and Restoration Techniques

    PubMed Central

    Richter, Dustin L.; Schenck, Robert C.; Wascher, Daniel C.; Treme, Gehron

    2015-01-01

    Context: Isolated chondral and osteochondral defects of the knee are a difficult clinical challenge, particularly in younger patients for whom alternatives such as partial or total knee arthroplasty are rarely advised. Numerous surgical techniques have been developed to address focal cartilage defects. Cartilage treatment strategies are characterized as palliation (eg, chondroplasty and debridement), repair (eg, drilling and microfracture [MF]), or restoration (eg, autologous chondrocyte implantation [ACI], osteochondral autograft [OAT], and osteochondral allograft [OCA]). Evidence Acquisition: PubMed was searched for treatment articles using the keywords knee, articular cartilage, and osteochondral defect, with a focus on articles published in the past 5 years. Study Design: Clinical review. Level of Evidence: Level 4. Results: In general, smaller lesions (<2 cm2) are best treated with MF or OAT. Furthermore, OAT shows trends toward greater longevity and durability as well as improved outcomes in high-demand patients. Intermediate-size lesions (2-4 cm2) have shown fairly equivalent treatment results using either OAT or ACI options. For larger lesions (>4 cm2), ACI or OCA have shown the best results, with OCA being an option for large osteochondritis dissecans lesions and posttraumatic defects. Conclusion: These techniques may improve patient outcomes, though no single technique can reproduce normal hyaline cartilage. PMID:26502188

  2. Depletion of Gangliosides Enhances Articular Cartilage Repair in Mice

    PubMed Central

    Matsuoka, Masatake; Onodera, Tomohiro; Homan, Kentaro; Sasazawa, Fumio; Furukawa, Jun-ichi; Momma, Daisuke; Baba, Rikiya; Hontani, Kazutoshi; Joutoku, Zenta; Matsubara, Shinji; Yamashita, Tadashi; Iwasaki, Norimasa

    2017-01-01

    Elucidation of the healing mechanisms in damaged tissues is a critical step for establishing breakthroughs in tissue engineering. Articular cartilage is clinically one of the most successful tissues to be repaired with regenerative medicine because of its homogeneous extracellular matrix and few cell types. However, we only poorly understand cartilage repair mechanisms, and hence, regenerated cartilage remains inferior to the native tissues. Here, we show that glycosylation is an important process for hypertrophic differentiation during articular cartilage repair. GM3, which is a precursor molecule for most gangliosides, was transiently expressed in surrounding damaged tissue, and depletion of GM3 synthase enhanced cartilage repair. Gangliosides also regulated chondrocyte hypertrophy via the Indian hedgehog pathway. These results identify a novel mechanism of cartilage healing through chondrocyte hypertrophy that is regulated by glycosylation. Manipulation of gangliosides and their synthases may have beneficial effects on articular cartilage repair. PMID:28252046

  3. Articular cartilage: structural and developmental intricacies and questions

    PubMed Central

    Koyama, Eiki; Pacifici, Maurizio

    2015-01-01

    Articular cartilage has obvious and fundamental roles in joint function and body movement. Much is known about its organization, extracellular matrix and phenotypic properties of its cells, but less is known about its developmental biology. Incipient articular cartilage in late embryos and neonates is a thin tissue with scanty matrix and small cells, while adult tissue is thick and zonal and contains large cells and abundant matrix. What remains unclear is not only how incipient articular cartilage forms, but how it then grows and matures into a functional, complex and multifaceted structure. This review focuses on recent and exciting discoveries on the developmental biology and growth of articular cartilage, frames them within the context of classic studies, and points to lingering questions and research goals. Advances in this research area will have significant relevance to basic science, and also considerable translational value to design superior cartilage repair and regeneration strategies. PMID:26408155

  4. 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

  5. [Allograft of cultured chondrocytes into articular cartilage defects in rabbits--experimental study of the repair of articular cartilage injuries].

    PubMed

    Tsuge, H; Sasaki, T; Susuda, K; Abe, K

    1983-08-01

    Articular cartilage defects were created by dill holes, 2 mm wide and 3 mm deep, through the articular cartilage into the subchondral bone in the patellar groove of the femur in mature rabbits. The defects received graft of cultured chondrocytes and the matrix obtained from the primary culture of chondrocytes isolated from the articular cartilage or auricular cartilage in immature rabbits. The isolated cells were cultured for 10 to 14 days. For graft, the cultured chondrocytes together with the matrix were detached from the culture chamber using rubber policemen and centrifuged. The repair of the grafted defects or defects without graft (control) was histologically studied 2 to 12 weeks after operation. The defects without the graft were progressively filled with fibrous tissue containing spindle shaped cells, fibers perpendicular to the surface, and matrix showing weak metachromasia with toluidin blue at 8 weeks. The defects received articular cartilage cell graft were occupied by new cartilage tissue consisting colonylike crumps of chondrocytes 2 weeks after operation. The crumps showed strong metachromasia with toluidin blue and strong stainability for safranin-O. By 4-8 weeks, the defects were filled with homogeneous cartilage. At 12 weeks, arrangement of the chondrocytes of the superficial layer of the new cartilage became columnar as seen in the normal articular cartilage. The defects received elastic cartilage cell graft were filled by reformed cartilage with chondrocytes surrounded by elastic fibers 2-12 weeks after operation. The results indicate that allograft of cultured chondrocytes with matrix into the articular cartilage defects accerated the repair process of the defects by formation of the new cartilage derived from the grafted chondrocytes.

  6. 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

  7. 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

    2015-10-29

    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.

  8. Quinolone arthropathy--acute toxicity to immature articular cartilage.

    PubMed

    Gough, A W; Kasali, O B; Sigler, R E; Baragi, V

    1992-01-01

    A class effect of quinolone antibacterial agents observed during animal toxicity testing is a specific arthropathy (QAP). Despite the growing list of laboratory animals susceptible to QAP and reports of arthralgia in patients treated with quinolones, the potential for QAP development in humans remains unknown. This review discusses current concepts in the biology of articular cartilage and how these concepts elucidate QAP pathogenesis. Biomechanical forces within synovial joints and toxicokinetic properties of quinolones contribute to QAP induction. Since a limited number of mechanistic pathways exist for acute articular damage, QAP may serve as a research tool to probe the pathobiology of injury to articular cartilage.

  9. Biomechanical Properties of Peripheral Layer in Articular Cartilage

    NASA Astrophysics Data System (ADS)

    Petrtyl, M.; Danesova, J.; Lisal, J.; Sejkotova, J.

    2010-05-01

    Articular cartilage as a complex viscohyperelastic biomaterial possessing supporting and protective functions. It transfers dynamic effects into subchondral and spongious bone and protects chondrocytes (and the matrix material) from their destruction. Under cyclic loads, it also ensures regulated long-term protection of articular cartilage plateaus. The viscoelastic properties of the peripheral zone of articular cartilage and its molecular structure ensure the regulation of the transport and accumulation of synovial fluid between articular plateaus. The viscoelastic properties of articular cartilage in the peripheral zone ensure that during cyclic loading some amount of synovial fluid is always retained accumulated between articular plateaus, which were presupplemented with it in the previous loading cycle. During long-term harmonic cyclic loading and unloading, the strains stabilize at limit values. Shortly after loading, the strain rate is always greater than before unloading. In this way, the hydrodynamic lubrication biomechanism quickly presupplements the surface localities with lubrication material. Shortly after unloading, the strain rate is high. During strain relaxation, it slows down.

  10. Review: tissue engineering for regeneration of articular cartilage.

    PubMed

    Temenoff, J S; Mikos, A G

    2000-03-01

    Joint pain due to cartilage degeneration is a serious problem, affecting people of all ages. Although many techniques, often surgical, are currently employed to treat this affliction, none have had complete success. Recent advances in biology and materials science have pushed tissue engineering to the forefront of new cartilage repair techniques. This review seeks to condense information for the biomaterialist interested in developing materials for this application. Articular cartilage anatomy, types of injury, and current repair methods are explained. The need for biomaterials, current commonly used materials for tissue-engineered cartilage, and considerations in scale-up of cell-biomaterial constructs are summarized.

  11. Extraction of high-quality RNA from human articular cartilage.

    PubMed

    Le Bleu, Heather K; Kamal, Fadia A; Kelly, Meghan; Ketz, John P; Zuscik, Michael J; Elbarbary, Reyad A

    2017-02-01

    Extracting high-quality RNA from articular cartilage is challenging due to low cellularity and high proteoglycan content. This problem hinders efficient application of RNA sequencing (RNA-seq) analysis in studying cartilage homeostasis. Here we developed a method that purifies high-quality RNA directly from cartilage. Our method optimized the collection and homogenization steps so as to minimize RNA degradation, and modified the conventional TRIzol protocol to enhance RNA purity. Cartilage RNA purified using our method has appropriate quality for RNA-seq experiments including an RNA integrity number of ∼8. Our method also proved efficient in extracting high-quality RNA from subchondral bone.

  12. 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.

  13. Human stem cells and articular cartilage tissue engineering.

    PubMed

    Stoltz, J-F; Huselstein, C; Schiavi, J; Li, Y Y; Bensoussan, D; Decot, V; De Isla, N

    2012-12-01

    Injuries to articular cartilage are one of the most challenging issues of musculoskeletal medicine due to the poor intrinsic ability of this tissue for repair. Despite progress in orthopaedic surgery, cell-based surgical therapies such as autologous chondrocyte transplantation (ACT) have been in clinical use for cartilage repair for over a decade but this approach has shown mixed results. Moreover, the lack of efficient modalities of treatment for large chondral defects has prompted research on cartilage tissue engineering combining cells, scaffold materials and environmental factors. This paper focuses on the main parameters in tissue engineering and in particular, on the potential of mesenchymal stem cells (MSCs) as an alternative to cells derived from patient tissues in autologous transplantation and tissue engineering. We discussed the prospects of using autologous chondrocytes or MSCs in regenerative medicine and summarized the advantages and disadvantages of these cells in articular cartilage engineering.

  14. The bioactivity of cartilage extracellular matrix in articular cartilage regeneration.

    PubMed

    Sutherland, Amanda J; Converse, Gabriel L; Hopkins, Richard A; Detamore, Michael S

    2015-01-07

    Cartilage matrix is a promising material for cartilage regeneration given the evidence supporting its chondroinductive character. The "raw materials" of cartilage matrix can serve as building blocks and signals for tissue regeneration. These matrices can be created by chemical or physical processing: physical methods disrupt cellular membranes and nuclei but may not fully remove all cell components and DNA, whereas chemical methods combined with physical methods are effective in fully decellularizing such materials. It is important to delineate between the sources of the cartilage matrix, that is, derived from matrix in vitro or from native tissue, and then to further characterize the cartilage matrix based on the processing method, decellularization or devitalization. With these distinctions, four types of cartilage matrices exist: decellularized native cartilage (DCC), devitalized native cartilage (DVC), decellularized cell-derived matrix (DCCM), and devitalized cell-derived matrix (DVCM). One currently marketed cartilage matrix device is decellularized, although trends in patents suggest additional decellularized products may be available in the future. To identify the most relevant source and processing for cartilage matrix, testing needs to include targeting the desired application, optimizing delivery of the material, identify relevant FDA regulations, assess availability of materials, and immunogenic properties of the product.

  15. MRI appearance of normal articular cartilage.

    PubMed

    Goodwin, Douglas W

    2011-05-01

    At each joint, the extracellular matrix of cartilage is arranged in a complex and characteristic organization that is specific for that joint. This structure exerts a strong influence on the appearance of magnetic resonance (MR) images through orientation-related alterations in T2 decay. As a result, the MR appearance of cartilage at each joint is predictable and specific for that joint. The diagnostic utility of MR imaging for evaluating cartilage is enhanced when the acquisition and review of the images is informed by an understanding of this relationship between normal structure and the MR appearance of cartilage.

  16. The Bioactivity of Cartilage Extracellular Matrix in Articular Cartilage Regeneration

    PubMed Central

    Sutherland, Amanda J.; Converse, Gabriel L.; Hopkins, Richard A.; Detamore, Michael S.

    2014-01-01

    Cartilage matrix is a particularly promising acellular material for cartilage regeneration given the evidence supporting its chondroinductive character. The ‘raw materials’ of cartilage matrix can serve as building blocks and signals for enhanced tissue regeneration. These matrices can be created by chemical or physical methods: physical methods disrupt cellular membranes and nuclei but may not fully remove all cell components and DNA, whereas chemical methods when combined with physical methods are particularly effective in fully decellularizing such materials. Critical endpoints include no detectable residual DNA or immunogenic antigens. It is important to first delineate between the sources of the cartilage matrix, i.e., derived from matrix produced by cells in vitro or from native tissue, and then to further characterize the cartilage matrix based on the processing method, i.e., decellularization or devitalization. With these distinctions, four types of cartilage matrices exist: decellularized native cartilage (DCC), devitalized native cartilage (DVC), decellularized cell derived matrix (DCCM), and devitalized cell derived matrix (DVCM). Delivery of cartilage matrix may be a straightforward approach without the need for additional cells or growth factors. Without additional biological additives, cartilage matrix may be attractive from a regulatory and commercialization standpoint. Source and delivery method are important considerations for clinical translation. Only one currently marketed cartilage matrix medical device is decellularized, although trends in filed patents suggest additional decellularized products may be available in the future. To choose the most relevant source and processing for cartilage matrix, qualifying testing needs to include targeting the desired application, optimizing delivery of the material, identify relevant FDA regulations, assess availability of raw materials, and immunogenic properties of the product. PMID:25044502

  17. Advanced cell therapies for articular cartilage regeneration.

    PubMed

    Madeira, Catarina; Santhagunam, Aruna; Salgueiro, João B; Cabral, Joaquim M S

    2015-01-01

    Advanced cell-based therapies are promising approaches for stimulating full regeneration of cartilage lesions. In addition to a few commercially available medicinal products, several clinical and preclinical studies are ongoing worldwide. In preclinical settings, high-quality cartilage tissue has been produced using combination strategies involving stem or progenitor cells, biomaterials, and biomolecules to generate a construct for implantation at the lesion site. Cell numbers and mechanical stimulation of the constructs are not commonly considered, but are important parameters to be evaluated in forthcoming clinical studies. We review current clinical and preclinical studies for advanced therapy cartilage regeneration and evaluate the progress of the field.

  18. Solute transport across the articular surface of injured cartilage.

    PubMed

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

    2013-07-15

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

  19. 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

  20. 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.

  1. Permeability and shear modulus of articular cartilage in growing mice.

    PubMed

    Berteau, J-Ph; Oyen, M; Shefelbine, S J

    2016-02-01

    Articular cartilage maturation is the postnatal development process that adapts joint surfaces to their site-specific biomechanical demands. Understanding the changes in mechanical tissues properties during growth is a critical step in advancing strategies for orthopedics and for cell- and biomaterial- based therapies dedicated to cartilage repair. We hypothesize that at the microscale, the articular cartilage tissue properties of the mouse (i.e., shear modulus and permeability) change with the growth and are dependent on location within the joint. We tested cartilage on the medial femoral condyle and lateral femoral condyle of seven C57Bl6 mice at different ages (2, 3, 5, 7, 9, 12, and 17 weeks old) using a micro-indentation test. Results indicated that permeability decreased with age from 2 to 17 weeks. Shear modulus reached a peak at the end of the growth (9 weeks). Within an age group, shear modulus was higher in the MFC than in the LFC, but permeability did not change. We have developed a method that can measure natural alterations in cartilage material properties in a murine joint, which will be useful in identifying changes in cartilage mechanics with degeneration, pathology, or treatment.

  2. 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

  3. Biochemical composition of the superficial layer of articular cartilage.

    PubMed

    Crockett, R; Grubelnik, A; Roos, S; Dora, C; Born, W; Troxler, H

    2007-09-15

    To gain more information on the mechanism of lubrication in articular joints, the superficial layer of bovine articular cartilage was mechanically removed in a sheet of ice that formed on freezing the cartilage. Freeze-dried samples contained low concentrations of chondroitin sulphate and protein. Analysis of the protein by SDS PAGE showed that the composition of the sample was comparable to that of synovial fluid (SF). Attenuated total reflection infrared (ATR-IR) spectroscopy of the dried residue indicated that the sample contained mostly hyaluronan. Moreover, ATR-IR spectroscopy of the upper layer of the superficial layer, adsorbed onto silicon, showed the presence of phospholipids. A gel could be formed by mixing hyaluronan and phosphatidylcholine in water with mechanical properties similar to those of the superficial layer on cartilage. Much like the superficial layer of natural cartilage, the surface of this gel became hydrophobic on drying out. Thus, it is proposed that the superficial layer forms from hyaluronan and phospholipids, which associate by hydrophobic interactions between the alkyl chains of the phospholipids and the hydrophobic faces of the disaccharide units in hyaluronan. This layer is permeable to material from the SF and the cartilage, as shown by the presence of SF proteins and chondroitin sulphate. As the cartilage dries out after removal from the joint, the phospholipids migrate towards the surface of the superficial layer to reduce the surface tension. It is also proposed that the highly efficient lubrication in articular joints can, at least in part, be attributed to the ability of the superficial layer to adsorb and hold water on the cartilage surface, thus creating a highly viscous boundary protection.

  4. Elastic and osmotic properties of articular cartilage

    NASA Astrophysics Data System (ADS)

    Lin, David; Dimitriadis, Emilios; Horkayne-Szakaly, Iren; Horkay, Ferenc

    2006-03-01

    The pathophysiology of osteoarthritis involves cellular and biochemical processes linked to mechanical stress. A better understanding of the mechanism of these processes and how they cause changes in the composition, macro- and micro-structure, and mechanical properties of cartilage is necessary for developing effective preventative and treatment strategies. In this study, elastic and osmotic swelling properties of tissue-engineered cartilage were explored using atomic force microscopy (AFM) and a tissue osmometer. AFM was also used to image the surface of the specimens while chemical composition was determined by biochemical analysis. Estimation of the Young's moduli of the tissue from AFM force-indentation data was performed using an optimization approach to fit appropriate models to the data. Force-indentation data were acquired both with sharp, pyramidal and with microspherical probes. The procedure has been validated by making measurements on model gel systems of known elastic properties. This approach is presented as a robust method of optimally extracting Young's moduli of soft, crosslinked materials from AFM data. Gross inhomogeneities at different scales in the cartilage tissue are manifested in the high degree of variance in local Young's moduli values obtained from both AFM and osmotic swelling data. These findings suggest that the mechanical properties of cartilage are affected by the local macromolecular composition.

  5. Effects of Articular Cartilage Constituents on Phosphotungstic Acid Enhanced Micro-Computed Tomography

    PubMed Central

    Karhula, Sakari S.; Finnilä, Mikko A.; Lammi, Mikko J.; Ylärinne, Janne H.; Kauppinen, Sami; Rieppo, Lassi; Pritzker, Kenneth P. H.; Nieminen, Heikki J.; Saarakkala, Simo

    2017-01-01

    Contrast-enhanced micro-computed tomography (CEμCT) with phosphotungstic acid (PTA) has shown potential for detecting collagen distribution of articular cartilage. However, the selectivity of the PTA staining to articular cartilage constituents remains to be elucidated. The aim of this study was to investigate the dependence of PTA for the collagen content in bovine articular cartilage. Adjacent bovine articular cartilage samples were treated with chondroitinase ABC and collagenase to degrade the proteoglycan and the collagen constituents in articular cartilage, respectively. Enzymatically degraded samples were compared to the untreated samples using CEμCT and reference methods, such as Fourier-transform infrared imaging. Decrease in the X-ray attenuation of PTA in articular cartilage and collagen content was observed in cartilage depth of 0–13% and deeper in tissue after collagen degradation. Increase in the X-ray attenuation of PTA was observed in the cartilage depth of 13–39% after proteoglycan degradation. The X-ray attenuation of PTA-labelled articular cartilage in CEμCT is associated mainly with collagen content but the proteoglycans have a minor effect on the X-ray attenuation of the PTA-labelled articular cartilage. In conclusion, the PTA labeling provides a feasible CEμCT method for 3D characterization of articular cartilage. PMID:28135331

  6. Increasing the Dose of Autologous Chondrocytes Improves Articular Cartilage Repair

    PubMed Central

    Guillén-García, Pedro; Rodríguez-Iñigo, Elena; Guillén-Vicente, Isabel; Caballero-Santos, Rosa; Guillén-Vicente, Marta; Abelow, Stephen; Giménez-Gallego, Guillermo

    2014-01-01

    Background: We hypothesized that implanting cells in a chondral defect at a density more similar to that of the intact cartilage could induce them to synthesize matrix with the features more similar to that of the uninjured one. Methods: We compared the implantation of different doses of chondrocytes: 1 million (n = 5), 5 million (n = 5), or 5 million mesenchymal cells (n = 5) in the femoral condyle of 15 sheep. Tissue generated by microfracture at the trochlea, and normal cartilage from a nearby region, processed as the tissues resulting from the implantation, were used as references. Histological and molecular (expression of type I and II collagens and aggrecan) studies were performed. Results: The features of the cartilage generated by implantation of mesenchymal cells and elicited by microfractures were similar and typical of a poor repair of the articular cartilage (presence of fibrocartilage, high expression of type I collagen and a low mRNA levels of type II collagen and aggrecan). Nevertheless, in the samples obtained from tissues generated by implantation of chondrocytes, hyaline-like cartilage, cell organization, low expression rates of type I collagen and high levels of mRNA corresponding to type II collagen and aggrecan were observed. These histological features, show less variability and are more similar to those of the normal cartilage used as control in the case of 5 million cells implantation than when 1 million cells were used. Conclusions: The implantation of autologous chondrocytes in type I/III collagen membranes at high density could be a promising tool to repair articular cartilage. PMID:26069691

  7. 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

  8. Ultrasonic quantitation of superficial degradation of articular cartilage.

    PubMed

    Saarakkala, Simo; Töyräs, Juha; Hirvonen, Jani; Laasanen, Mikko S; Lappalainen, Reijo; Jurvelin, Jukka S

    2004-06-01

    Ultrasound (US) has been suggested as a means for the quantitative detection of early osteoarthrotic changes in articular cartilage. In this study, the ability of quantitative US 2-D imaging (20 MHz) to reveal superficial changes in bovine articular cartilage after mechanical or enzymatic degradation was investigated in vitro. Mechanical degradation was induced by grinding samples against an emery paper with the grain size of 250 microm, 106 microm, 45 microm or 23 microm. For enzymatic degradation, samples were digested with collagenase, trypsin or chondroitinase ABC. Variations of the US reflection coefficient induced by the degradation were investigated. Furthermore, two novel parameters, the US roughness index (URI) and the spatial variation of the US reflection coefficient (SVR), were established to quantitate the integrity of the cartilage surface. Statistically significant decreases (p < 0.05) in US reflection coefficient were observed after mechanical degradations or enzymatic digestion with collagenase. Increases (p < 0.05) in URI were also revealed after these treatments. We conclude that quantitative US imaging may be used to detect collagen disruption and increased roughness in the articular surface. These structural damages are typical of early osteoarthrosis.

  9. 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

  10. Emerging options for treatment of articular cartilage injury in the athlete.

    PubMed

    Mithoefer, Kai; McAdams, Timothy R; Scopp, Jason M; Mandelbaum, Bert R

    2009-01-01

    Articular cartilage injury is observed with increasing frequency in both elite and amateur athletes and results from the significant joint stress associated particularly with high-impact sports. The lack of spontaneous healing of these joint surface defects leads to progressive joint pain and mechanical symptoms with resulting functional impairment and limitation of athletic participation. Left untreated, articular cartilage defects can lead to chronic joint degeneration and athletic disability. Articular cartilage repair in athletes requires effective and durable joint surface restoration that can withstand the significant joint stresses generated during athletic activity. Several techniques for articular cartilage repair have been developed recently, which can successfully restore articular cartilage surfaces and allow for return to high-impact athletics after articular cartilage injury. Besides these existing techniques, new promising scientific concepts and techniques are emerging that incorporate modern tissue engineering technologies and promise further improvement for the treatment of these challenging injuries in the demanding athletic population.

  11. Hydrogel-Based Controlled Delivery Systems for Articular Cartilage Repair

    PubMed Central

    Madry, Henning

    2016-01-01

    Delivery of bioactive factors is a very valuable strategy for articular cartilage repair. Nevertheless, the direct supply of such biomolecules is limited by several factors including rapid degradation, the need for supraphysiological doses, the occurrence of immune and inflammatory responses, and the possibility of dissemination to nontarget sites that may impair their therapeutic action and raise undesired effects. The use of controlled delivery systems has the potential of overcoming these hurdles by promoting the temporal and spatial presentation of such factors in a defined target. Hydrogels are promising materials to develop delivery systems for cartilage repair as they can be easily loaded with bioactive molecules controlling their release only where required. This review exposes the most recent technologies on the design of hydrogels as controlled delivery platforms of bioactive molecules for cartilage repair. PMID:27642587

  12. Contrast agent enhanced pQCT of articular cartilage

    NASA Astrophysics Data System (ADS)

    Kallioniemi, A. S.; Jurvelin, J. S.; Nieminen, M. T.; Lammi, M. J.; Töyräs, J.

    2007-02-01

    The delayed gadolinium enhanced MRI of cartilage (dGEMRIC) technique is the only non-invasive means to estimate proteoglycan (PG) content in articular cartilage. In dGEMRIC, the anionic paramagnetic contrast agent gadopentetate distributes in inverse relation to negatively charged PGs, leading to a linear relation between T1,Gd and spatial PG content in tissue. In the present study, for the first time, contrast agent enhanced peripheral quantitative computed tomography (pQCT) was applied, analogously to dGEMRIC, for the quantitative detection of spatial PG content in cartilage. The suitability of two anionic radiographic contrast agents, gadopentetate and ioxaglate, to detect enzymatically induced PG depletion in articular cartilage was investigated. First, the interrelationships of x-ray absorption, as measured with pQCT, and the contrast agent solution concentration were investigated. Optimal contrast agent concentrations for the following experiments were selected. Second, diffusion rates for both contrast agents were investigated in intact (n = 3) and trypsin-degraded (n = 3) bovine patellar cartilage. The contrast agent concentration of the cartilaginous layer was measured prior to and 2-27 h after immersion. Optimal immersion time for the further experiments was selected. Third, the suitability of gadopentetate and ioxaglate enhanced pQCT to detect the enzymatically induced specific PG depletion was investigated by determining the contrast agent concentrations and uronic acid and water contents in digested and intact osteochondral samples (n = 16). After trypsin-induced PG loss (-70%, p < 0.05) the penetration of gadopentetate and ioxaglate increased (p < 0.05) by 34% and 48%, respectively. Gadopentetate and ioxaglate concentrations both showed strong correlation (r = -0.95, r = -0.94, p < 0.01, respectively) with the uronic acid content. To conclude, contrast agent enhanced pQCT provides a technique to quantify PG content in normal and experimentally

  13. 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

  14. 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.

  15. Genesis and morphogenesis of limb synovial joints and articular cartilage.

    PubMed

    Decker, Rebekah S; Koyama, Eiki; Pacifici, Maurizio

    2014-10-01

    Limb synovial joints are intricate structures composed of articular cartilage, synovial membranes, ligaments and an articular capsule. Together, these tissues give each joint its unique shape, organization and biomechanical function. Articular cartilage itself is rather complex and organized in distinct zones, including the superficial zone that produces lubricants and contains stem/progenitor cells. For many years there has been great interest in deciphering the mechanisms by which the joints form and come to acquire such unique structural features and diversity. Decades ago, classic embryologists discovered that the first overt sign of joint formation at each prescribed limb site was the appearance of a dense and compact population of mesenchymal cells collectively called the interzone. Work carried out since then by several groups has provided evidence that the interzone cells actively participate in joint tissue formation over developmental time. This minireview provides a succinct but comprehensive description of the many important recent advances in this field of research. These include studies using various conditional reporter mice to genetically trace and track the origin, fate and possible function of joint progenitor cells; studies on the involvement and roles in signaling pathways and transcription factors in joint cell determination and functioning; and studies using advanced methods of gene expression analyses to uncover novel genetic determinants of joint formation and diversity. The overall advances are impressive, and the findings are not only of obvious interest and importance but also have major implications in the conception of future translational medicine tools to repair and regenerate defective, overused or aging joints.

  16. The Influence of Articular Cartilage Thickness Reduction on Meniscus Biomechanics

    PubMed Central

    Łuczkiewicz, Piotr; Daszkiewicz, Karol; Chróścielewski, Jacek; Witkowski, Wojciech; Winklewski, Pawel J.

    2016-01-01

    Objective Evaluation of the biomechanical interaction between meniscus and cartilage in medial compartment knee osteoarthritis. Methods The finite element method was used to simulate knee joint contact mechanics. Three knee models were created on the basis of knee geometry from the Open Knee project. We reduced the thickness of medial cartilages in the intact knee model by approximately 50% to obtain a medial knee osteoarthritis (OA) model. Two variants of medial knee OA model with congruent and incongruent contact surfaces were analysed to investigate the influence of congruency. A nonlinear static analysis for one compressive load case was performed. The focus of the study was the influence of cartilage degeneration on meniscal extrusion and the values of the contact forces and contact areas. Results In the model with incongruent contact surfaces, we observed maximal compressive stress on the tibial plateau. In this model, the value of medial meniscus external shift was 95.3% greater, while the contact area between the tibial cartilage and medial meniscus was 50% lower than in the congruent contact surfaces model. After the non-uniform reduction of cartilage thickness, the medial meniscus carried only 48.4% of load in the medial compartment in comparison to 71.2% in the healthy knee model. Conclusions We have shown that the change in articular cartilage geometry may significantly reduce the role of meniscus in load transmission and the contact area between the meniscus and cartilage. Additionally, medial knee OA may increase the risk of meniscal extrusion in the medial compartment of the knee joint. PMID:27936066

  17. Effects of ageing on the biomechanical properties of rat articular cartilage.

    PubMed

    Wang, L; Kalu, D N; Banu, J; Thomas, J B; Gabriel, N; Athanasiou, K

    2006-05-01

    Previous studies have demonstrated that male Sprague Dawley (SD) rats experience age-related bone loss with the same characteristics as that in ageing men. As articular cartilage, like bone, is a critical component of the health and function of the musculoskeletal system, the authors hypothesized that articular cartilage in the untreated male SD rats could be a suitable model for studying the age-related deterioration of articular cartilage in men. To test this hypothesis, male SD rats were killed at between 6 and 27 months. The right femur of each rat was removed. The effects of ageing on the structural integrity of the distal femoral articular cartilage were studied by biomechanical testing with a creep indentation apparatus. The aggregate modulus, Poisson's ratio, permeability, thickness, and percentage recovery of articular cartilage were determined using finite element/non-linear optimization modelling. No significant differences were observed in these biomechanical properties of the distal femoral articular cartilage as a function of age. Therefore, untreated male SD rats appear to be unsuitable for studying the age-related changes of articular cartilage as they occur in men. However, and more intriguingly, it is also possible that ageing does not affect the biomechanical properties of articular cartilage in the absence of cartilage pathology.

  18. Measurements of surface layer of the articular cartilage using microscopic techniques

    NASA Astrophysics Data System (ADS)

    Ryniewicz, A. M.; Ryniewicz, A.; Ryniewicz, W.; Gaska, A.

    2010-07-01

    The articular cartilage is the structure that directly cooperates tribologically in biobearing. It belongs to the connective tissues and in the joints it assumes two basic forms: hyaline cartilage that builds joint surfaces and fibrocartilage which may create joint surfaces. From this fibrocartilage are built semilunar cartilage and joint disc are built as well. The research of articular cartilage have been done in macro, micro and nano scale. In all these measurement areas characteristic features occur which can identify biobearing tribology. The aim of the research was the identification of surface layer of articular cartilage by means of scanning electron microscopy (SEM) and atom force microscopy (AFM) and the analysis of topography of these layers. The material used in the research of surface layer was the animal articular cartilage: hyaline cartilage and fibrocartilage.

  19. Oxidative DNA damage in osteoarthritic porcine articular cartilage

    PubMed Central

    Chen, Antonia F.; Davies, Catrin M.; De Lin, Ming; Fermor, Beverley

    2008-01-01

    Purpose Osteoarthritis (OA) is associated with increased levels of reactive oxygen species. This study investigated if increased oxidative DNA damage accumulates in OA articular cartilage compared with non-OA articular cartilage from pigs with spontaneous OA. Additionally, the ability of nitric oxide (NO) or peroxynitrite (ONOO-) induced DNA damage in non-OA chondrocytes to undergo endogenous repair was investigated. Methods Porcine femoral condyles were graded for the stage of OA, macroscopically by the Collins Scale, and histologically by the modified Mankin Grade. Levels of DNA damage were determined in non-OA and OA cartilage, using the comet assay. For calibration, DNA damage was measured by exposing non-OA chondrocytes to 0-12 Gray of x-ray irradiation. Non-OA articular chondrocytes were treated with 0-500 μM of NO donors (NOC-18 or SIN-1), and DNA damage assessed after treatment and 5 days recovery. Results A significant increase (p<0.01) in oxidative DNA damage occurred in OA chondrocytes in joints with Mankin Grades 3 or greater, compared to non-OA chondrocytes. The percentage of nuclei containing DNA damage increased significantly (p<0.001) from early to late grades of OA. An increase of approximately 0.65-1.7 breaks/1000kB of DNA occurred in OA, compared to non-OA nuclei. NOC-18 or SIN-1 caused significant DNA damage (p<0.001) in non-OA chondrocytes that did not undergo full endogenous repair after 5 days (p<0.05). Conclusion Our data suggest significant levels of oxidative DNA damage occur in OA chondrocytes that accumulates with OA progression. Additionally, DNA damage induced by NO and ONOO- in non-OA chondrocytes does not undergo full endogenous repair. PMID:18720406

  20. Ultrasound attenuation in normal and spontaneously degenerated articular cartilage.

    PubMed

    Nieminen, Heikki J; Saarakkala, Simo; Laasanen, Mikko S; Hirvonen, Jani; Jurvelin, Jukka S; Töyräs, Juha

    2004-04-01

    High-frequency ultrasound (US) measurements may provide means for the quantification of articular cartilage quality. Bovine patellar cartilage samples (n = 32) at various degenerative stages were studied using US attenuation measurements in the 5- to 9-MHz frequency range. The results were compared with the histologic, biochemical and mechanical parameters obtained for the same samples, to identify which structural or functional factors could be related to the attenuation and its variations. Attenuation, as calculated in the frequency or time domain, correlated significantly with the histologic tissue integrity (i.e., Mankin score, Spearman r = -0.576 or -0.571, p < 0.01), but the slope of attenuation vs. frequency was not related to Mankin score. Ultrasound speed was, however, the most sensitive indicator of Mankin score (r = -0.755, p < 0.01). Cartilage quality index (CQI), a combination of structural and functional parameters, correlated significantly with the attenuation or speed (r = -0.655 or -0.872, p < 0.01). Our results suggest that US attenuation and speed may be suited for the diagnostics of cartilage degeneration. (E-mail: )

  1. 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.

  2. 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

  3. Temporary immobilisation facilitates repair of chemically induced articular cartilage injury.

    PubMed Central

    Williams, J M; Brandt, K D

    1984-01-01

    Recent studies have indicated that immobilisation of the lower limb may prevent surface fibrillation and osteophyte formation, and reduce cell depletion, following injection of iodoacetate into the ipsilateral knee of the guinea-pig. The present study shows that temporary immobilisation also facilitates repair of the damaged cartilage during a subsequent period of remobilisation in which the animal is permitted to move 'on all fours'. Thus, in animals killed six weeks after a single intra-articular injection of iodoacetate (0.3 mg in 0.1 ml saline), and in which the injected knee had been immobilised for three weeks, Safranin-O staining of the articular cartilage was more intense, chondrocyte density greater, and osteophytosis much less marked than in animals injected with iodoacetate but killed immediately after the three weeks immobilisation period. By contrast, immobilisation for only one week failed to protect against degenerative changes and osteophytes caused by iodoacetate injection. Immobilisation alone produced no apparent pathological changes in animals which did not receive iodoacetate. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:6735906

  4. Lubrication mode analysis of articular cartilage using Stribeck surfaces.

    PubMed

    Gleghorn, Jason P; Bonassar, Lawrence J

    2008-01-01

    Lubrication of articular cartilage occurs in distinct modes with various structural and biomolecular mechanisms contributing to the low-friction properties of natural joints. In order to elucidate relative contributions of these factors in normal and diseased tissues, determination and control of lubrication mode must occur. The objectives of these studies were (1) to develop an in vitro cartilage on glass test system to measure friction coefficient, mu; (2) to implement and extend a framework for the determination of cartilage lubrication modes; and (3) to determine the effects of synovial fluid on mu and lubrication mode transitions. Patellofemoral groove cartilage was linearly oscillated against glass under varying magnitudes of compressive strain utilizing phosphate buffered saline (PBS) and equine and bovine synovial fluid as lubricants. The time-dependent frictional properties were measured to determine the lubricant type and strain magnitude dependence for the initial friction coefficient (mu(0)=mu(t-->0)) and equilibrium friction coefficient (mu(eq)=mu(t-->infinity)). Parameters including tissue-glass co-planarity, normal strain, and surface speed were altered to determine the effect of the parameters on lubrication mode via a 'Stribeck surface'. Using this testing apparatus, cartilage exhibited biphasic lubrication with significant influence of strain magnitude on mu(0) and minimal influence on mu(eq), consistent with hydrostatic pressurization as reported by others. Lubrication analysis using 'Stribeck surfaces' demonstrated clear regions of boundary and mixed modes, but hydrodynamic or full film lubrication was not observed even at the highest speed (50mm/s) and lowest strain (5%).

  5. 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.

  6. Multiscale Mechanics of Articular Cartilage: Potentials and Challenges of Coupling Musculoskeletal, Joint, and Microscale Computational Models

    PubMed Central

    Halloran, J. P.; Sibole, S.; van Donkelaar, C. C.; van Turnhout, M. C.; Oomens, C. W. J.; Weiss, J. A.; Guilak, F.; Erdemir, A.

    2012-01-01

    Articular cartilage experiences significant mechanical loads during daily activities. Healthy cartilage provides the capacity for load bearing and regulates the mechanobiological processes for tissue development, maintenance, and repair. Experimental studies at multiple scales have provided a fundamental understanding of macroscopic mechanical function, evaluation of the micromechanical environment of chondrocytes, and the foundations for mechanobiological response. In addition, computational models of cartilage have offered a concise description of experimental data at many spatial levels under healthy and diseased conditions, and have served to generate hypotheses for the mechanical and biological function. Further, modeling and simulation provides a platform for predictive risk assessment, management of dysfunction, as well as a means to relate multiple spatial scales. Simulation-based investigation of cartilage comes with many challenges including both the computational burden and often insufficient availability of data for model development and validation. This review outlines recent modeling and simulation approaches to understand cartilage function from a mechanical systems perspective, and illustrates pathways to associate mechanics with biological function. Computational representations at single scales are provided from the body down to the microstructure, along with attempts to explore multiscale mechanisms of load sharing that dictate the mechanical environment of the cartilage and chondrocytes. PMID:22648577

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

    PubMed

    Chan, Deva D; Neu, Corey P

    2013-01-06

    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.

  8. The joint synovium: A critical determinant of articular cartilage fate in inflammatory joint diseases.

    PubMed

    Bhattaram, Pallavi; Chandrasekharan, Unnikrishnan

    2017-02-01

    The synovium constitutes the envelope of articular joints and is a critical provider of synovial fluid components and articular cartilage nutrients. Its inflammation is a predominant feature and cause of joint degeneration in diseases as diverse as rheumatoid, psoriatic, juvenile and idiopathic arthritis, and lupus, gout and lyme disease. These inflammatory joint diseases (IJDs) are due to a wide variety of genetic, epigenetic and environmental factors that trigger, promote, and perpetuate joint destabilization. In spite of this variety of causes, IJDs share main pathological features, namely inflammation of the joint synovium (synovitis) and progressive degeneration of articular cartilage. In addition to being a driving force behind the destruction of articular cartilage in IJD, synovitis is also increasingly being recognized as a significant contributor of articular cartilage degeneration in osteoarthritis, a disease primarily due to aging- or trauma-related wear and tear of cartilage surfaces. In view of this important role of the synovium in determining the fate of articular cartilage, this review focuses on its underlying mechanisms in the pathology of IJD. We address the roles of synovial fibroblasts, macrophages and endothelial cells in the maintenance of joint health and in the destruction of articular cartilage integrity during IJD. Molecular mechanisms that have been recently shown to govern the pathological activities of the resident synovial cells are highlighted. Finally, advantages and disadvantages of targeting these new molecular mechanisms for preventing cartilage degeneration due to chronic inflammation are also discussed.

  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. 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.

  11. Loading of Articular Cartilage Compromises Chondrocyte Respiratory Function

    PubMed Central

    Coleman, Mitchell C.; Ramakrishnan, Prem S.; Brouillette, Marc J.; Martin, James A.

    2015-01-01

    Objective Determine whether repeatedly overloading healthy cartilage disrupts mitochondrial function in a manner similar to that associated with osteoarthritis pathogenesis. Methods We exposed normal articular cartilage on bovine osteochondral explants to 1 day or 7 consecutive days of cyclic axial compression (0.25 or 1.0 MPa, 0.5 Hz, 3 hours) and evaluated effects on chondrocyte viability, ATP concentration, reactive oxygen species (ROS) production, indicators of oxidative stress, respiration, and mitochondrial membrane potential. Results Neither 0.25 nor 1.0 MPa cyclic compression caused extensive chondrocyte death, macroscopic tissue damage, or overt changes in stress-strain behavior. After one day of loading, differences in respiratory activities between the 0.25 and 1.0 MPa groups were minimal; after 7 loading days, however, respiratory activity and ATP levels were suppressed in the 1.0 MPa group relative to the 0.25 MPa group, an effect prevented with pretreatment with 10 mM N-acetylcysteine. These changes were accompanied by increased proton leakage and decreases in mitochondrial membrane potential as well as by increased ROS formation indicated by dihydroethidium staining and glutathione oxidation. Conclusion Repeated overloading leads to chondrocyte oxidant-dependent mitochondrial dysfunction. This mitochondrial dysfunction may contribute to destabilization of cartilage during various stages of OA in distinct ways by disrupting chondrocyte anabolic responses to mechanical stimuli. PMID:26473613

  12. 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.

  13. Conditional Deletion of the Phd2 Gene in Articular Chondrocytes Accelerates Differentiation and Reduces Articular Cartilage Thickness

    PubMed Central

    Cheng, Shaohong; Pourteymoor, Sheila; Alarcon, Catrina; Mohan, Subburaman

    2017-01-01

    Based on our findings that PHD2 is a negative regulator of chondrocyte differentiation and that hypoxia signaling is implicated in the pathogenesis of osteoarthritis, we investigated the consequence of disruption of the Phd2 gene in chondrocytes on the articular cartilage phenotype in mice. Immunohistochemistry detected high expression of PHD2 in the superficial zone (SZ), while PHD3 and HIF-1α (target of PHD2) are mainly expressed in the middle-deep zone (MDZ). Conditional deletion of the Phd2 gene (cKO) in chondrocytes accelerated the transition of progenitors to hypertrophic (differentiating) chondrocytes as revealed by reduced SZ thickness, and increased MDZ thickness, as well as increased chondrocyte hypertrophy. Immunohistochemistry further revealed decreased levels of progenitor markers but increased levels of hypertrophy markers in the articular cartilage of the cKO mice. Treatment of primary articular chondrocytes, in vitro, with IOX2, a specific inhibitor of PHD2, promoted articular chondrocyte differentiation. Knockdown of Hif-1α expression in primary articular chondrocytes using lentiviral vectors containing Hif-1α shRNA resulted in reduced expression levels of Vegf, Glut1, Pgk1, and Col10 compared to control shRNA. We conclude that Phd2 is a key regulator of articular cartilage development that acts by inhibiting the differentiation of articular cartilage progenitors via modulating HIF-1α signaling. PMID:28349987

  14. Ultrasound speed and attenuation in progressive trypsin digested articular cartilage.

    PubMed

    Niu, HaiJun; Li, LiFeng; Sun, Feng; Yan, Yan; Wang, YueXiang; Li, DeYu; Fan, YuBo

    2011-11-01

    Subtle changes of articular cartilage (AC) can lead to tissue degeneration and even osteoarthritis (OA). The early degeneration of AC is closely related to a change in proteoglycans (PG) content. The observation of PG is therefore an appropriate way of studying OA and evaluating the degree of AC degeneration. In this study, 20 cartilage-bone samples were prepared from normal porcine femoral condyle cartilage and 10 samples were digested over 2 h using 0.25% trypsin solution. The dynamic process of PG-digestion was explored using a conventional A-mode ultrasound (US) experimental system with a 10 MHz center frequency. Quantitative acoustic parameters were calculated from ultrasonic radio-frequency echo signals and included US speed (USS), US amplitude attenuation coefficient (UAA) and broadband US attenuation coefficient (BUA). The experimental results showed that the conventional A-mode ultrasound is valuable for tracking the degree of PG-digestion. Histology also confirmed the validity of the ultrasound observations. For every AC sample, the degree of PG-digestion within a given time was different and was affected by individual differences. After two hours of degeneration, USS showed a mean decrease of 0.4% (P<0.05). UAA was significantly lower after a two-hour PG depletion period (from (2.45±0.23) to (2.28±0.41) dB mm⁻¹). BUA showed no significant differences during this process. In conclusion, conventional ultrasound can provide useful information about trypsin-induced progressive PG depletion in AC and can reflect variations of PG content via the quantitative acoustic parameters USS and UAA. The results of this study may be used to identify an indirect indicator of cartilage matrix integrity and OA disease progression.

  15. Binding and lubrication of biomimetic boundary lubricants on articular cartilage.

    PubMed

    Samaroo, Kirk J; Tan, Mingchee; Putnam, David; Bonassar, Lawrence J

    2017-03-01

    The glycoprotein, lubricin, is the primary boundary lubricant of articular cartilage and has been shown to prevent cartilage damage after joint injury. In this study, a library of eight bottle-brush copolymers were synthesized to mimic the structure and function of lubricin. Polyethylene glycol (PEG) grafted onto a polyacrylic acid (pAA) core mimicked the hydrophilic mucin-like domain of lubricin, and a thiol terminus anchored the polymers to cartilage surfaces much like lubricin's C-terminus. These copolymers, abbreviated as pAA-g-PEG, rapidly bound to cartilage surfaces with binding time constants ranging from 20 to 39 min, and affected lubrication under boundary mode conditions with coefficients of friction ranging from 0.140 ± 0.024 to 0.248 ± 0.030. Binding and lubrication were highly correlated (r(2)  = 0.89-0.99), showing that boundary lubrication in this case strongly depends on the binding of the lubricant to the surface. Along with time-dependent and dose-dependent behavior, lubrication and binding of the lubricin-mimetics also depended on copolymer structural parameters including pAA backbone length, PEG side chain length, and PEG:AA brush density. Polymers with larger backbone sizes, brush sizes, or brush densities took longer to bind (p < 0.05). Six of the eight polymers reduced friction relative to denuded cartilage plugs (p < 0.05), suggesting their potential to lubricate and protect cartilage in vivo. In copolymers with shorter pAA backbones, increasing hydrodynamic size inhibited lubrication (p < 0.08), while the opposite was observed in copolymers with longer backbones (p < 0.05). These polymers show similar in vitro lubricating efficacy as recombinant lubricins and as such have potential for in vivo treatment of post-traumatic osteoarthritis. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:548-557, 2017.

  16. Changes in Proton Dynamics in Articular Cartilage Caused by Phosphate Salts and Fixation Solutions.

    PubMed

    Zheng, Shaokuan; Xia, Yang

    2010-01-01

    The objective was to study the effect of phosphate salts and fixation solutions on the proton dynamics in articular cartilage in vitro. Microscopic magnetic resonance imaging (μMRI) T(2) anisotropy and nuclear magnetic resonance (NMR) double quantum-filtered (DQF) spectroscopy were used to study the full-thickness articular cartilage from several canine humeral heads. The in-plane pixel size across the depth of the cartilage tissue was 13 μm. The acid phosphate salt was an effective exchange catalyst for proton exchange in the cartilage with an organized structure of collagen fibrils, while the alkaline phosphate salt was not. For cartilage tissue containing less organized collagen fibrils, both acid and alkaline phosphate salts have no significant effect on the T(2) value at low concentration but decrease the T(2) value at high concentration. The solutions of NaCl, KCl, CaCl(2), and D-PBS were found to have no significant effect on T(2) and DQF in cartilage. This study demonstrates the ability to modify the proton exchange in articular cartilage using the solutions of phosphate salts. The ability to modify the proton exchange in articular cartilage can be used to modulate the laminar appearance of articular cartilage in MRI.

  17. 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.

  18. Protective Mechanism of Articular Cartilage to Severe Loading: Roles of Lubricants, Cartilage Surface Layer, Extracellular Matrix and Chondrocyte

    NASA Astrophysics Data System (ADS)

    Murakami, Teruo; Sawae, Yoshinori; Ihara, Maki

    The natural synovial joints have excellent tribological performance known as very low friction and very low wear for various daily activities in human life. These functions are likely to be supported by the adaptive multimode lubrication mechanism, in which the various lubrication modes such as elastohydrodynamic lubrication, weeping, boundary and gel film lubrication appear to operate to protect articular cartilage, depending on the severity of the rubbing conditions. In this paper, various protective roles of synovial fluid, cartilage surface layer, extracellular matrix and chondrocyte to severe loading are described. In the first part, the protective mechanism by adsorbed films and underlying gel films was described on the basis of the frictional behaviors of articular cartilage against articular cartilage or glass. It was discussed that the replenishment of gel film removed during severe rubbing is likely to be controlled by supply of proteoglycan from the extracellular matrix, where the chondrocyte plays the main role in the metabolism. In the second part, the time-dependent local deformation of biphasic articular cartilage under constant total compressive strain condition was evaluated in the finite element analyses. The importance of clarification of actual stress-strain in chondrocyte was indicated in relation to the tribological property of articular cartilage.

  19. 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

  20. 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.

  1. Pannocytes: distinctive cells found in rheumatoid arthritis articular cartilage erosions.

    PubMed Central

    Zvaifler, N. J.; Tsai, V.; Alsalameh, S.; von Kempis, J.; Firestein, G. S.; Lotz, M.

    1997-01-01

    A distinctive cell was identified from sites of rheumatoid arthritis cartilage injury. Similar cells are not found in lesions of osteoarthritis cartilage. We have designated them as pannocytes (PCs). Their rhomboid morphology differs from the bipolar shape of fibroblast-like synoviocytes or the spherical configuration of primary human articular chondrocytes. Chondrocytes are short-lived, whereas the original PC line grew for 25 passages before becoming senescent. Features in common with cultured primary chondrocytes include maximal proliferation in response to transforming growth factor-beta a catabolic response to interleukin-1 beta, collagenase production, and mRNA for the induced lymphocyte antigen and inducible nitric oxide synthase. Despite the presence of the inducible nitric oxide synthase message, PCs do not produce NO either constitutively or when cytokine stimulated. Each of the mesenchymal cells, fibroblast-like synoviocytes, primary chondrocytes, and PCs have the gene for type I collagen, but the type II collagen gene is detected only in primary chondrocytes. PCs can be distinguished from fibroblast-like synoviocytes and primary chondrocytes by their morphology, bright VCAM-1 staining, and growth response to cytokines and growth factors. Their prolonged life span in vitro suggests that PCs might represent an earlier stage of mesenchymal cell differentiation, and they could have a heretofore unrecognized role in rheumatoid arthritis joint destruction. Images Figure 1 Figure 2 Figure 7 Figure 8 Figure 10 PMID:9060847

  2. Mesenchymal Stem Cells and Articular Cartilage Repair: Clinical Studies and Future Direction

    PubMed Central

    Punwar, Shahid; Khan, Wasim S

    2011-01-01

    Cartilage is frequently injured but shows little capacity for repair. Current treatment options include the use of procedures that stimulate repair through the stimulation of subchondral bone marrow and result in the formation of fibrocartilage. There is considerable interest in the use of cell-based treatment strategies and there are limited studies describing the use of mesenchymal stem cells for cartilage repair with promising early results. This paper reviews the current treatment strategies for articular cartilage, describes use of mesenchymal stem cells for articular cartilage repair along with the results of clinical studies, and describes the future direction that these strategies are likely to take. PMID:21886696

  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.

  4. ARTICULAR CARTILAGE TENSILE INTEGRITY: MODULATION BY MATRIX DEPLETION IS MATURATION-DEPENDENT

    PubMed Central

    Asanbaeva, Anna; Tam, Johnny; Schumacher, Barbara L.; Klisch, Stephen M.; Masuda, Koichi; Sah, Robert L.

    2008-01-01

    Articular cartilage function depends on the molecular composition and structure of its extracellular matrix (ECM). The collagen network (CN) provides cartilage with tensile integrity, but must also remodel during growth. Such remodeling may depend on matrix molecules interacting with the CN to modulate the tensile behavior of cartilage. The objective of this study was to determine the effects of increasingly selective matrix depletion on tensile properties of immature and mature articular cartilage, and thereby establish a framework for identifying molecules involved in CN remodeling. Depletion of immature cartilage with guanidine, chondroitinase ABC, chondroitinase AC, and Streptomyces hyaluronidase markedly increased tensile integrity, while the integrity of mature cartilage remained unaltered after depletion with guanidine. The enhanced tensile integrity after matrix depletion suggests that certain ECM components of immature matrix serve to inhibit CN interactions and may act as modulators of physiological alterations of cartilage geometry and tensile properties during growth/maturation. PMID:18394422

  5. A noncontacting method for material property determination for articular cartilage from osmotic loading.

    PubMed Central

    Narmoneva, D A; Wang, J Y; Setton, L A

    2001-01-01

    Articular cartilage is one of several biological tissues in which swelling effects are important in tissue mechanics and function, and may serve as an indicator of degenerative joint disease. This work presents a new approach to quantify swelling effects in articular cartilage, as well as to determine the material properties of cartilage from a simple free-swelling test. Samples of nondegenerate and degenerate human patellar cartilage were subjected to osmotic loading by equilibrating the tissue in solutions of varying osmolarity. The resulting swelling-induced strains were measured using a noncontacting optical method. A theoretical formulation of articular cartilage in a free-swelling configuration was developed based on an inhomogeneous, triphasic mechano-chemical model. Optimization of the model predictions to the experimental data was performed to determine two parameters descriptive of material stiffness at the surface and deeper cartilage layers, and a third parameter descriptive of thickness of the cartilage surface layer. These parameters were used to determine the thickness-averaged uniaxial modulus of cartilage, H(A). The obtained values for H(A) were similar to those for the tensile modulus of human cartilage reported in the literature. Degeneration resulted in an increase in thickness of the region of "apparent cartilage softening," and a decrease in the value for uniaxial modulus at this layer. These findings provide important evidence that collagen matrix disruption starts at the articular surface and progresses into the deeper layers with continued degeneration. These results suggest that the method provides a means to quantify the severity and depth of degenerative changes in articular cartilage. This method may also be used to determine material properties of cartilage in small joints in which conventional testing methods are difficult to apply. PMID:11720975

  6. Human adipose-derived mesenchymal progenitor cells engraft into rabbit articular cartilage.

    PubMed

    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

    2015-05-27

    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.

  7. 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

  8. Influence of dynamic load on friction behavior of human articular cartilage, stainless steel and polyvinyl alcohol hydrogel as artificial cartilage.

    PubMed

    Li, Feng; Su, Yonglin; Wang, Jianping; Wu, Gang; Wang, Chengtao

    2010-01-01

    Many biomaterials are being developed to be used for cartilage substitution and hemiarthroplasty implants. The lubrication property is a key feature of the artificial cartilage. The frictional behavior of human articular cartilage, stainless steel and polyvinyl alcohol (PVA) hydrogel were investigated under cartilage-on-PVA hydrogel contact, cartilage-on-cartilage contact and cartilage-on-stainless steel contact using pin-on-plate method. Tests under static load, cyclic load and 1 min load change were used to evaluate friction variations in reciprocating motion. The results showed that the lubrication property of cartilage-on-PVA hydrogel contact and cartilage-on-stainless steel contact were restored in both 1 min load change and cyclic load tests. The friction coefficient of PVA hydrogel decreased from 0.178 to 0.076 in 60 min, which was almost one-third of the value under static load in continuous sliding tests. In each test, the friction coefficient of cartilage-on-cartilage contact maintained far lower value than other contacts. It is indicated that a key feature of artificial cartilage is the biphasic lubrication properties.

  9. Subchondral route for nutrition to articular cartilage in the rabbit. Measurement of diffusion with hydrogen gas in vivo.

    PubMed

    Ogata, K; Whiteside, L A; Lesker, P A

    1978-10-01

    The route of nutrients going to articular cartilage was studied by determining the diffusion of hydrogen molecules from the subchondral circulation to the articular cartilage in rabbits. In all immature animals there was diffusion of hydrogen from subchondral bone into articular cartilage, while in the older immature animals the results were variable. None of the mature animals showed any diffusion of hydrogen into articular cartilage. The rate of diffusion of hydrogen was significantly lower in the articular cartilage than in the subchondral bone in the immature animals while the concentrations of hydrogen in the articular cartilage were only fractions of those in the subchondral bone at the same instant. Histologically, the deep layers of immature cartilage are penetrated extensively by vascular buds from the ossified portion of the epiphysis, while in adults the articular cartilage is separated from subchondral vascular spaces by an end-plate of bone. Blood vessels penetrating into the basilar layer of articular cartilage in immature animals appear to play an important role in the nutrition of articular cartilage coming from the subchondral region.

  10. Articular Cartilage Repair: Where We Have Been, Where We Are Now, and Where We Are Headed.

    PubMed

    Grande, Daniel A; Schwartz, John A; Brandel, Eric; Chahine, Nadeen O; Sgaglione, Nicholas

    2013-10-01

    This review traces the genealogy of the field of articular cartilage repair from its earliest attempts to its present day vast proliferation of research advances. Prior to the 1980s there was only sporadic efforts to regenerate articular cartilage as it was considered to be incapable of regeneration based on historical dogma. The first flurry of reports documented the use of various cell types ultimately leading to the first successful demonstration of autologous chondrocyte transplantation which was later translated to clinical use and has resulted in the revised axiom that cartilage regeneration is possible. The current field of cartilage repair is multifaceted and some of the 1980s' vintage concepts have been revisited with state of the art technology now available. The future of the field is now poised to undertake the repair of whole cartilage surfaces beyond focal defects and an appreciation for integrated whole joint health to restore cartilage homeostasis.

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

    PubMed

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

    2014-01-03

    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.

  12. [Agrecan and articular cartilage: assessment of glycosyltransferases for the restoration of cartilage matrix in osteoarthritis].

    PubMed

    Magdalou, Jacques; Netter, Patrick; Fournel-Gigleux, Sylvie; Ouzzine, Mohamed

    2008-01-01

    Articular cartilage is a connective tissue containing a single type of cells, chondrocytes, which synthesise a dense extracellular matrix, mainly composed of collagens, hyaluronic acid and proteoglycans. These macromolecules play a major role in the resistance and elastic properties of the tissue. They also favour interactions with small active substances, such as growth factors and cytokines. Chondrocytes have a low metabolic capacity in relatively hypoxic conditions and absence of vascular supply. In physiopathological conditions, such as osteoarthritis (OA), progressive and irreversible degradation of matrix components is occurring. With the aim of developing new and efficient therapies against OA, we investigated the molecular mechanisms that initiate the disease, in order to identify key-proteins. These targets should hopefully lead to the design of new drugs able to stop degradation and restore cartilage. One of the earliest molecular events in OA is the degradation of aggrecan, the most abundant proteoglycan. The glycosaminoglycan (GAG) chains, chondroitin-sulfate, attached on the core protein, are subjected to hydrolysis into smaller fragments. We were interested in the glycosyltransferases that catalyse the formation of the polysaccharidic chains, namely those involved in the common tetrasaccharidic protein linkage region, GlcAbeta1,3Galbeta1,3Galbeta 1,4Xyl-O-Serine. The galactose beta1,3-glucuronosyltransférase-I (GlcAT-I) which catalyses the final step of this primer and which is markedly repressed during OA is an attractive target in that respect. Indeed, the human recombinant enzyme was found to play a pivotal role in GAG synthesis. Moreover, overexpression of GlcAT-I in cartilage explants treated with IL1beta was able to fully counteract proteoglycan depletion induced by the cytokine. These results prompted us to investigate the structure, function and regulation of this enzyme. This study provides the basis for several therapy approaches (gene

  13. 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

  14. Platelet interaction with modified articular cartilage. Its possible relevance to joint repair.

    PubMed Central

    Zucker-Franklin, D; Drosenberg, L

    1977-01-01

    During studies concerned with the platelet-collagen interaction, it was observed that platelets did not adhere to bovine or human articular cartilage and that cartilage did not induce platelet aggregation in vivo or in vitro. To study the mechanism responsible for this observation, the role of proteoglycans was examined. Purified cartilage collagen proved to be fully active as a platelet aggregant. Addition of small amounts of proteoglycan subunit (PGS) blocked platelet aggregation, whereas chondroitin sulfate, a major glycosaminoglycan component of cartilage matrix, impaired platelet aggregation only at concentrations which resulted in a marked increase in viscosity. Moreover, PGS abolished aggregation of platelets by polylysine but did not prevent aggregation by ADP, suggesting that PGS may block strategically placed lysine sites on the collagen molecule. Treatment of fresh articular cartilage with proteolytic enzymes rendered the tissue active as a platelet aggregant. In vivo experiments demonstrated that surgical scarification of rabbit articular cartilage does not result in adhesion of autologous platelets. Treatment of rabbit knee joints with intraarticular trypsin 1 wk before the injection of blood resulted in adhesion and aggregation of platelets on the surface of the lesions. Since there is evidence from other studies that some degree of cartilage healing may take place after initiation of an inflammatory response, it is postulated that induction of platelet-cartilage interaction may eventuate in cartilage repair. Images PMID:557500

  15. Influence of biological scaffold regulation on the proliferation of chondrocytes and the repair of articular cartilage

    PubMed Central

    Wang, Si-Qun; Xia, Jun; Chen, Jie; Lu, Jian-Xi; Wei, Yi-Bing; Chen, Fei-Yan; Huang, Gang-Yong; Shi, Jing-Sheng; Yu, Yong-Lin

    2016-01-01

    Purpose: To investigate the effects of hard tissue engineering scaffold (the material is β-TCP) with different micro-structures on the proliferation of chondrocytes, and the influence of its composite erythrocytes on the repair of articular cartilage defects. Methods: Rabbit cartilage cells were on β-TCP bioceramic scaffold with different micro-structures in vitro, the proliferation growth trend of chondrocytes within the scaffold was calculated, and a optimal micro-structure suitable for cartilage cell growth was determined. Composite chondrocytes were implanted into rabbit models of articular cartilage defects, and the repair situation was observed. Results: the bioceramic scaffold with an inner diameter of 120 μm and an aperture of 500-630 μm was suitable for the growth of cartilage cells. Scaffold loaded with second generation of cartilage cell suspension got a top histological score of 20.76±2.13, which was closely similar to that of normal cartilage. Conclusion: When loaded with the second generation of cartilage cells, the β-TCP biological ceramic scaffold with a pore size of 500-630 μm, and an inner diameter of 120 μm, shows a best repairing effect on animal articular cartilage defects. PMID:27904662

  16. 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.

  17. Development of hybrid scaffolds using ceramic and hydrogel for articular cartilage tissue regeneration.

    PubMed

    Seol, Young-Joon; Park, Ju Young; Jeong, Wonju; Kim, Tae-Ho; Kim, Shin-Yoon; Cho, Dong-Woo

    2015-04-01

    The regeneration of articular cartilage consisting of hyaline cartilage and hydrogel scaffolds has been generally used in tissue engineering. However, success in in vivo studies has been rarely reported. The hydrogel scaffolds implanted into articular cartilage defects are mechanically unstable and it is difficult for them to integrate with the surrounding native cartilage tissue. Therefore, it is needed to regenerate cartilage and bone tissue simultaneously. We developed hybrid scaffolds with hydrogel scaffolds for cartilage tissue and with ceramic scaffolds for bone tissue. For in vivo study, hybrid scaffolds were press-fitted into osteochondral tissue defects in a rabbit knee joints and the cartilage tissue regeneration in blank, hydrogel scaffolds, and hybrid scaffolds was compared. In 12th week after implantation, the histological and immunohistochemical analyses were conducted to evaluate the cartilage tissue regeneration. In the blank and hydrogel scaffold groups, the defects were filled with fibrous tissues and the implanted hydrogel scaffolds could not maintain their initial position; in the hybrid scaffold group, newly generated cartilage tissues were morphologically similar to native cartilage tissues and were smoothly connected to the surrounding native tissues. This study demonstrates hybrid scaffolds containing hydrogel and ceramic scaffolds can provide mechanical stability to hydrogel scaffolds and enhance cartilage tissue regeneration at the defect site.

  18. Investigation of polarization-sensitive optical coherence tomography towards the study of microstructure of articular cartilage

    NASA Astrophysics Data System (ADS)

    Kasaragod, Deepa; Lu, Zenghai; Le Maitre, Christine; Wilkinson, J. Mark; Matcher, Stephen

    2013-03-01

    This paper highlights the extended Jones matrix calculus based multi-angle study carried out to understand the depth dependent structural orientation of the collagen fibers in articular cartilage using polarization-sensitive optical coherence tomography (PS-OCT). A 3D lamellar model for the collagen fiber orientation, with a quadratic profile for the arching of the collagen fibers in transitional zone which points towards an ordered arrangement of fibers in that zone is the basis of the organization architecture of collagen fibers in articular cartilage. Experimental data for both ex-vivo bovine fetlock and human patellar cartilage samples are compared with theoretical predictions, with a good quantitative agreement for bovine and a reasonable qualitative agreement for human articular cartilage samples being obtained

  19. Articular cartilage defects in the knee--basics, therapies and results.

    PubMed

    Fritz, Jürgen; Janssen, Pia; Gaissmaier, Christoph; Schewe, Bernhard; Weise, Kuno

    2008-04-01

    Full-thickness defects of the articular cartilage in the knee joint have lower regenerative properties than chondral lesions of the ankle. In order to avoid early osteoarthritis, symptomatic articular cartilage defects in younger patients should undergo biological reconstruction as soon as possible. Various surgical procedures are available to biologically resurface the articular joint line. Numerous animal experiments and clinical studies have shown that early biological reconstruction of circumscribed cartilage defects in the knee is superior to conservative or delayed surgical treatment. This superiority refers not only to defect healing but also to the elimination of changes following secondary osteoarthritis. The various surgical procedures can be differentiated by the range of indications and the final outcome. Additional malalignment, meniscus tears and/or ligament instabilities should be treated simultaneously with the cartilage resurfacing. The mid- and long-term results of the various current techniques are promising, but further modifications and improvements are needed.

  20. 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.

  1. Grossly apparent cartilage erosion of the patellar articular surface in dogs with congenital medial patellar luxation.

    PubMed

    Daems, R; Janssens, L A; Béosier, Y M

    2009-01-01

    One hundred and forty-five stifles of client-owned dogs that underwent corrective surgery for congenital medial patellar luxation were inspected for cartilage erosion on the articular surface of the patella. The lesions were mapped in surface percentage ranges of 20% and by location. Two-thirds of the patellae had cartilage erosion. Cartilage erosion varied between 0 and 100% of the total patellar articular surface and was localised mainly on the medial and distal side of the patella. Dogs with Grade IV patellar luxations and heavier dogs were more affected. The majority of dogs in our study with congenital medial patellar luxation had grossly apparent cartilage erosion on the articular surface of the patella, which may help to explain why certain patients do not function well clinically after technically successful corrective surgery.

  2. 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

  3. Effects of freezing rates and cryoprotectant on thermal expansion of articular cartilage during freezing process.

    PubMed

    Xu, Y; Sun, H J; Lv, Y; Zou, J C; Lin, B L; Hua, T C

    2013-01-01

    The intact articular cartilage has not yet been successfully preserved at low temperature most likely due to the volume expansion from water to ice during freezing. The objective of this current study focuses on examining thermal expansion behavior of articular cartilage (AC) during freezing from 0 degree C to -100 degree C. Thermo Mechanical Analysis (TMA) was used to investigate the effects of different concentrations of dimethyl sulphoxide (DMSO) (0%, 10%, 30% and 60% v/v) and different freezing rates (1 C/min, 3 C/min and 5 C/min). The results showed that: (1) the inhomogeneous thermal expansion (or contraction) presents due to inhomogeneous water distributions in articular cartilage during freezing, which also may be the most likely reason that the matrix has been damaged in cryopreserved intact articular cartilage; (2) at the phase transition temperature range, the maximum thermal strain change value for 5C/min is approximately 1.45 times than that for 1 C/min, but the maximum thermal expansion coefficient of the later is about six times than that of the former; (3) the thermal expansion coefficient decreases with increasing cooling rate at the unfrozen temperature region, but some opposite results are obtained at the frozen temperature region; (4) the higher the DMSO concentration is, at the phase change temperature region, the smaller the thermal strain change as well as the maximum thermal expansion coefficient are, but DMSO concentration exhibits little effect on the thermal expansion coefficient at both unfrozen and frozen region. Once the DMSO concentration increasing enough, e.g. 60% v/v, the thermal strain decreases linearly and smoothly without any abrupt change due to little or no ice crystal forms (i.e. vitrification) in frozen articular cartilage. This study may improve our understanding of the thermal expansion (or contraction) behavior of cryopreserved articular cartilage and it may be useful for the future study on cryopreservation of intact

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

    NASA Astrophysics Data System (ADS)

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

    2016-11-01

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

  5. 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.

  6. Hypotonic challenge modulates cell volumes differently in the superficial zone of intact articular cartilage and cartilage explant.

    PubMed

    Turunen, Siru M; Lammi, Mikko J; Saarakkala, Simo; Koistinen, Arto; Korhonen, Rami K

    2012-05-01

    The objective of this study was to evaluate the effect of sample preparation on the biomechanical behaviour of chondrocytes. We compared the volumetric and dimensional changes of chondrocytes in the superficial zone (SZ) of intact articular cartilage and cartilage explant before and after a hypotonic challenge. Calcein-AM labelled SZ chondrocytes were imaged with confocal laser scanning microscopy through intact cartilage surfaces and through cut surfaces of cartilage explants. In order to clarify the effect of tissue composition on cell volume changes, Fourier Transform Infrared microspectroscopy was used for estimating the proteoglycan and collagen contents of the samples. In the isotonic medium (300 mOsm), there was a significant difference (p < 0.05) in the SZ cell volumes and aspect ratios between intact cartilage samples and cartilage explants. Changes in cell volumes at both short-term (2 min) and long-term (2 h) time points after the hypotonic challenge (180 mOsm) were significantly different (p < 0.05) between the groups. Further, proteoglycan content was found to correlate significantly (r(2) = 0.63, p < 0.05) with the cell volume changes in cartilage samples with intact surfaces. Collagen content did not correlate with cell volume changes. The results suggest that the biomechanical behaviour of chondrocytes following osmotic challenge is different in intact cartilage and in cartilage explant. This indicates that the mechanobiological responses of cartilage and cell signalling may be significantly dependent on the integrity of the mechanical environment of chondrocytes.

  7. 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

  8. Shock absorbing ability of articular cartilage and subchondral bone under impact compression.

    PubMed

    Malekipour, Fatemeh; Whitton, Chris; Oetomo, Denny; Lee, Peter Vee Sin

    2013-10-01

    Despite the important role of subchondral bone in maintaining the integrity of the overlying articular cartilage, little research has focused on measuring its mechanical behavior, particularly under injurious load conditions such as impact compression. In this study, the stiffness and the absorbed energy of subchondral bone were compared to that of its overlying cartilage by applying impact compression to equine cartilage-bone specimens. Deformations of the cartilage and subchondral bone were examined independently within the cartilage-bone unit by analyzing real-time images of cartilage-bone explants. Peak subchondral bone and cartilage stiffness (mean ± SD) were 800.7 ± 250.0 MPa and 119.9 ± 50.8 MPa respectively. The maximum absorbed energy per unit volume of subchondral bone was approximately 4 times lower than that of cartilage. Micro-computed tomography (μCT) images at 9 μm resolution revealed oblique fissures at the cartilage articular surface. At the cartilage-bone interface, micro-cracks as thin as 30 μm in width and micro-fractures of width 200 μm could be seen in the μCT images. The relative energy loss in bone was 76.5 ± 6.8% in specimens with bone fracture and 23.0 ± 20.4% in specimens without bone fracture. Our results indicate that both articular cartilage and subchondral bone absorb shock under impact compression, but the energy absorption of bone is much higher in specimens that fracture. This may spare the overlying cartilage from immediate injury, but is a potential risk for subsequent post-traumatic osteoarthritis (PTOA).

  9. Functional analysis of articular cartilage deformation, recovery, and fluid flow following dynamic exercise in vivo.

    PubMed

    Eckstein, F; Tieschky, M; Faber, S; Englmeier, K H; Reiser, M

    1999-10-01

    The function of articular cartilage depends on the interaction between the tissue matrix and the interstitial fluid bound to the proteoglycan molecules. Mechanical loading has been shown to be involved in both the metabolic regulation of chondrocytes and in matrix degeneration. The purpose of the present study was therefore to analyze the deformation, recovery, and fluid flow in human articular cartilage after dynamic loading in vivo. The patellae of 7 volunteers were imaged at physical rest and after performing knee bends, with a specifically optimized fat-suppressed FLASH-3D magnetic resonance (MR) sequence. To measure cartilage deformation, the total volume of the patellar cartilage was determined, employing 3D digital image analysis. Patellar cartilage deformation ranged from 2.4 to 8.6% after 50 knee bends, and from 2.4% to 8.5% after 100 knee bends. Repeated sets of dynamic exercise at intervals of 15 min did not cause further deformation. After 100 knee bends, the cartilage required more than 90 min to recover from loading. The rate of fluid flow during relaxation ranged from 1.1 to 3.5 mm(3)/min (0.08 to 0.22 mm(3)/min per square centimeter of the articular surface) and was highly correlated with the individual degree of deformation after knee bends. The data provide the first quantification of articular cartilage recovery and of the rate of fluid flow between the cartilage matrix and surrounding tissue in intact joints in vivo. Measurement in the living opens the possibility of relating interindividual variations of mechanical cartilage properties to the susceptibility of developing joint failure, to assess the load-partitioning between the fluid phase and solid cartilage matrix during load transfer, and to determine the role of mechanically induced fluid flow in the regulation of the metabolic activity of chondrocytes.

  10. 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.

  11. 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.

  12. Frictional response of bovine articular cartilage under creep loading following proteoglycan digestion with chondroitinase ABC.

    PubMed

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

    2006-02-01

    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 2500 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: micro(eq) = 0.19 +/- 0.02; control: micro(eq) = 0.12 +/- 0.03; p = 0.002), though the coefficient achieved immediately upon loading did not increase significantly (treated: micro(min) = 0.0053 +/- 0.0025; control: micro(min) = 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.

  13. 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.

  14. Circadian Clocks in Articular Cartilage and Bone: A Compass in the Sea of Matrices.

    PubMed

    Yang, Nan; Meng, Qing-Jun

    2016-10-01

    Temporally coordinated resorption and synthesis is the key to maintaining healthy bones. Articular cartilage is a highly specialized connective tissue within the joints that lines the surface of a long bone. Emerging evidence has suggested a critical role of the circadian system in controlling cartilage and bone biology. Articular cartilage is sparsely populated with chondrocytes, surrounded by abundant extracellular matrices that are synthesized and maintained solely by chondrocytes. Once damaged, the articular cartilage tissue has poor capacity for endogenous repair, leaving the joints prone to osteoarthritis, an age-related painful condition that affects millions of individuals worldwide. An important question is how articular cartilage has evolved its remarkable capacity to maintain homeostasis and withstand daily biomechanical challenges associated with resting/activity cycles. Equally important is how this avascular and aneural tissue senses time and uses this information to coordinate daily phases of metabolic activity and tissue remodeling/repair. Bone tissue derived from cartilage has similarly sparse populations of resident cells living in dense and largely mineralized matrices. We discuss recent progress on circadian clocks in these matrix-rich skeletal tissues and highlight avenues for future research.

  15. 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

  16. Impact testing to determine the mechanical properties of articular cartilage in isolation and on bone.

    PubMed

    Burgin, Leanne V; Aspden, Richard M

    2008-02-01

    The biomechanical response of cartilage to impact loads, both in isolation and in situ on its bone substrate, has been little studied despite the common occurrence of osteoarthritis subsequent to cartilage injury. An instrumented drop tower was used to apply controlled impact loads of different energies to explants of bovine articular cartilage. Results were compared with a conventional slow stress-strain test. The effects of the underlying bone were investigated by progressively shortening a core of bone removed with the cartilage, and by gluing cartilage samples to substrates of different moduli. The maximum dynamic modulus of isolated samples of bovine articular cartilage, at strain rates between 1100 and 1500 s(-1), was approximately two orders of magnitude larger than the quasistatic modulus and varied non-linearly with applied stress. When attached to a substrate of higher modulus, increasing the thickness of the substrate increased the effective modulus of the combination until a steady value was achieved. A lower modulus substrate reduced the effective modulus of the combination. Severe impacts resulted in damage to the bone rather than to the cartilage. The modulus of cartilage rises rapidly and non-linearly with strain rate, giving the tissue a remarkable ability to withstand impact loads. The presence of cartilage attenuated the peak force experienced by the bone and spread the impact loading period over a longer time.

  17. Biofunctional polymer nanoparticles for intra-articular targeting and retention in cartilage

    NASA Astrophysics Data System (ADS)

    Rothenfluh, Dominique A.; Bermudez, Harry; O'Neil, Conlin P.; Hubbell, Jeffrey A.

    2008-03-01

    The extracellular matrix of dense, avascular tissues presents a barrier to entry for polymer-based therapeutics, such as drugs encapsulated within polymeric particles. Here, we present an approach by which polymer nanoparticles, sufficiently small to enter the matrix of the targeted tissue, here articular cartilage, are further modified with a biomolecular ligand for matrix binding. This combination of ultrasmall size and biomolecular binding converts the matrix from a barrier into a reservoir, resisting rapid release of the nanoparticles and clearance from the tissue site. Phage display of a peptide library was used to discover appropriate targeting ligands by biopanning on denuded cartilage. The ligand WYRGRL was selected in 94 of 96 clones sequenced after five rounds of biopanning and was demonstrated to bind to collagen II α1. Peptide-functionalized nanoparticles targeted articular cartilage up to 72-fold more than nanoparticles displaying a scrambled peptide sequence following intra-articular injection in the mouse.

  18. 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.

  19. 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.

  20. 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

  1. Autoradiographic evidence of sup 125 I-. beta. -endorphin binding sites in the articular cartilage of the rat

    SciTech Connect

    Castano, M.T.; Freire-Garabal, M.; Giraldez, M.; Nunez, M.J.; Belmonte, A.; Couceiro, J.; Jorge, J. )

    1991-01-01

    After {sup 125}I-{beta}-endorphin was intravenously injected to rats, an autoradiographic study of distal femur articular cartilage was performed. Results show a specific binding of {sup 125}I-{beta}-endorphin to chondrocytes, suggesting the possible existence of an opiate modulation of articular cartilage.

  2. The rigid curette technique for the application of fibrin bioadhesive during hip arthroscopy for articular cartilage lesions.

    PubMed

    Asopa, Vipin; Singh, Parminder J

    2014-04-01

    Encouraging midterm results have recently been reported for the arthroscopic treatment of delaminating articular cartilage lesions at the capsulolabral junction of the hip joint using fibrin bioadhesive. The needle used to introduce the bioadhesive is long, flexible, and often difficult to position. We describe a novel technique for introducing the needle that allows accurate placement behind the delaminated articular cartilage pocket during hip arthroscopy.

  3. Type I collagen-based fibrous capsule enhances integration of tissue-engineered cartilage with native articular cartilage.

    PubMed

    Yang, Yueh-Hsun; Ard, Mary B; Halper, Jaroslava T; Barabino, Gilda A

    2014-04-01

    Successful integration of engineered constructs with host tissues is crucial for cartilage repair, yet achieving it remains challenging. A collagen I-based fibrous capsule characterized by increased cell density and decreased glycosaminoglycan deposition usually forms at the periphery of tissue-engineered cartilage. The current study aimed to evaluate the effects of a solid fibrous capsule on construct integration with native articular cartilage. To this end, capsule-containing (CC) and capsule-free (CF) constructs were grown by culturing chondrocyte-seeded scaffolds with insulin-like growth factor-1 and transforming growth factor-β1, respectively, in a wavy-walled bioreactor that imparts hydrodynamic forces for 4 weeks. The ability of harvested constructs to integrate with native cartilage was determined using a cartilage explant model. Our results revealed that adhesive stress between native cartilage and the CC constructs was 57% higher than that in the CF group, potentially due to the absence of glycosaminoglycans and increased cell density in the capsule region and deposition of denser and thicker collagen fibrils at the integration site. The present work demonstrates that the fibrous capsule can effectively enhance early integration of engineered and native cartilage tissues and thus suggests the need to include the capsule as a variable in the development of cartilage tissue engineering strategies.

  4. Sequential changes in the mechanical properties of viable articular cartilage stored in vitro

    SciTech Connect

    Thomas, V.J.; Jimenez, S.A.; Brighton, C.T.; Brown, N.

    1984-01-01

    Viable articular cartilage from the medial femoral condyles of rabbits was stored in vitro in tissue culture medium with various additives and the same site of each specimen was mechanically tested sequentially throughout a 12-day storage period. Indentation testing was performed with instantaneous and sustained loads. Preservation of sustained-load carrying capacity was observed in the condyles stored with additives, indicating maintenance of an intact cartilage matrix. However, initial testing with small sustained loads (preload) showed changes not observed at higher load levels. The changes noted at small sustained initial loads may reflect alterations in cartilage surface structure and may be an early indicator of its mechanical integrity. Chondrocyte viability and proteoglycan content, as measured by /sup 35/S incorporation and hexosamine concentration, were unchanged in comparison to fresh articular cartilage.

  5. [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.

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

    NASA Astrophysics Data System (ADS)

    Suponenkovs, Artjoms; Glazs, Aleksandrs; Platkajis, Ardis

    2017-03-01

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

  7. 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

  8. Regenerative Potential of Tissue-Engineered Nasal Chondrocytes in Goat Articular Cartilage Defects.

    PubMed

    Mumme, Marcus; Steinitz, Amir; Nuss, Katja M; Klein, Karina; Feliciano, Sandra; Kronen, Peter; Jakob, Marcel; von Rechenberg, Brigitte; Martin, Ivan; Barbero, Andrea; Pelttari, Karoliina

    2016-11-01

    Nasal chondrocytes (NC) were previously demonstrated to remain viable and to participate in the repair of articular cartilage defects in goats. Here, we investigated critical features of tissue-engineered grafts generated by NC in this large animal model, namely cell retention at the implantation site, architecture and integration with adjacent tissues, and effects on subchondral bone changes. In this study, isolated autologous goat NC (gNC) and goat articular chondrocytes (gAC, as control) were expanded, green fluorescent protein-labelled and seeded on a type I/III collagen membrane. After chondrogenic differentiation, tissue-engineered grafts were implanted into chondral defects (6 mm in diameter) in the stifle joint for 3 or 6 months. At the time of explantation, surrounding tissues showed no or very low (only in the infrapatellar fat pad <0.32%) migration of the grafted cells. In repair tissue, gNC formed typical structures of articular cartilage, such as flattened cells at the surface and column-like clusters in the middle layers. Semi-quantitative histological evaluation revealed efficient integration of the grafted tissues with the adjacent native cartilage and underlying subchondral bone. A significantly increased subchondral bone area, as a sign for the onset of osteoarthritis, was observed following treatment of cartilage defects with gAC-, but not with gNC-grafts. Our results reinforce the use of NC-based engineered tissue for articular cartilage repair and preliminarily indicate their potential for the treatment of early osteoarthritic defects.

  9. Depth and rate dependent mechanical behaviors for articular cartilage: experiments and theoretical predictions.

    PubMed

    Gao, Li-Lan; Zhang, Chun-Qiu; Gao, Hong; Liu, Zhi-Dong; Xiao, Peng-Peng

    2014-05-01

    An optimized digital image correlation (DIC) technique was applied to investigate the depth-dependent mechanical properties of articular cartilage and simultaneously the depth-dependent nonlinear viscoelastic constitutive model of cartilage was proposed and validated. The creep tests were performed with different stress levels and it is found that the initial strain and instantaneous strain increase; however the creep compliance decreases with the increase of compressive stress. The depth-dependent creep strain of cartilage was obtained by analyzing the images acquired using the optimized DIC technique. Moreover the inhomogeneous creep compliance distributions within the tissues were determined at different creep time points. It is noted that both creep strain and creep compliance with different creep times decrease from cartilage surface to deep. The depth-dependent creep compliance increases with creep time and the increasing amplitude of creep compliance decreases along cartilage depth. The depth-dependent and stress rate dependent nonlinear stress and strain curves were obtained for articular cartilage through uniaxial compression tests. It is found that the Young's modulus of cartilage increases obviously along cartilage depth from superficial layer to deep layer and the Young's modulus of different layers for cartilage increases with the increase of stress rate. The Poisson's ratio of cartilage increases along cartilage depth with given compressive strain and the Poisson's ratio of different layers decreases with the increase of compressive strain. The depth-dependent nonlinear viscoelastic constitutive model was proposed and some creep data were applied to determine the parameters of the model. The depth-dependent compressive behaviors of cartilage were predicted by the model and the results show that there are good agreements between the experimental data and predictions.

  10. 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

  11. Pulsed CO2 laser for intra-articular cartilage vaporization and subchondral bone perforation in horses

    NASA Astrophysics Data System (ADS)

    Nixon, Alan J.; Roth, Jerry E.; Krook, Lennart P.

    1991-05-01

    A pulsed carbon dioxide laser was used to vaporize articular cartilage in four horses, and perforate the cartilage and subchondral bone in four horses. Both intercarpal joints were examined arthroscopically and either a 1 cm cartilage crater or a series of holes was created in the third carpal bone of one joint. The contralateral carpus served as a control. The horses were evaluated clinically for 8 weeks, euthanatized and the joints examined radiographically, grossly, and histologically. Pulsed carbon dioxide laser vaporized cartilage readily but penetrated bone poorly. Cartilage vaporization resulted in no greater swelling, heat, pain on flexion, lameness, or synovial fluid reaction than the sham procedure. Laser drilling resulted in a shallow, charred hole with a tenacious carbon residue, and in combination with the thermal damage to deeper bone, resulted in increased swelling, mild lameness and a low-grade, but persistent synovitis. Cartilage removal by laser vaporization resulted in rapid regrowth with fibrous and fibrovascular tissue and occasional regions of fibrocartilage at week 8. The subchondral bone, synovial membrane, and draining lymph nodes appeared essentially unaffected by the laser cartilage vaporization procedure. Conversely, carbon dioxide laser drilling of subchondral bone resulted in poor penetration, extensive areas of thermal necrosis of bone, and significant secondary damage to the apposing articular surface of the radial carpal bone. The carbon dioxide laser is a useful intraarticular instrument for removal of cartilage and has potential application in inaccessible regions of diarthrodial joints. It does not penetrate bone sufficiently to have application in subchondral drilling.

  12. MR imaging of the articular cartilage of the knee.

    PubMed

    Goodwin, Douglas W

    2009-12-01

    Magnetic resonance (MR) imaging of the knee is capable of accurately identifying and characterizing cartilage injuries and degeneration. Optimal cartilage imaging requires an understanding of the relationship between cartilage structure and the MR image, acquisition of images with adequate resolution, a purposeful interrogation of the images by a reviewer possessing an understanding of the appearance of tissue pathology as well as common pitfalls and artifacts, and finally, the accurate and consistent reporting of results.

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

    PubMed Central

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

    2009-01-01

    Background: Articular chondrocytes have got a long lifespan but rarely divides after maturity. Thus, an articular cartilage has a limited capacity for repair. Periosteal grafts have chondrogenic potential and have been used to repair defects in the articular cartilage. The purpose of the present study is to investigate the differentiation of free periosteal grafts in the patellofemoral joint where the cambium layer faces the subchondral bone and to investigate the applicability of periosteal grafts in the reconstruction of articular surfaces. Materials and Methods: The study was carried out over a period of 1 year on 25 adult, male Indian rabbits after obtaining permission from the institutional animal ethical committee. A full-thickness osteochondral defect was created by shaving off the whole articular cartilage of the patella of the left knee. The defect thus created was grafted with free periosteal graft. The patella of the right knee was taken as a control where no grafting was done after shaving off the articular cartilage. The first animal was used to study the normal histology of the patellar articular cartilage and periosteum obtained from the medial surface of tibial condyle. Rest 24 animals were subjected to patellectomy, 4 each at serial intervals of 2, 4, 8, 16, 32 and 48 weeks and the patellar articular surfaces were examined macroscopically and histologically. Results: The grafts got adherent to the underlying patellar articular surface at the end of 4 weeks. Microscopically, graft incorporation could be appreciated at 4 weeks. Mesenchymal cells of the cambium layer were seen differentiating into chondrocytes by the end of 4 weeks in four grafts (100%) and they were arranged in a haphazard manner. Till the end of 8 weeks, the cellular arrangement was mostly wooly. At 16 weeks, one graft (25%) had wooly arrangement of chondrocytes and three grafts (75%) had columnar formation of cells. Same percentage was maintained at 32 weeks. Four grafts (100%) at

  14. Characterization of colony-forming cells in adult human articular cartilage.

    PubMed

    Ozbey, Ozlem; Sahin, Zeliha; Acar, Nuray; Ozcelik, Filiz Tepekoy; Ozenci, Alpay Merter; Koksoy, Sadi; Ustunel, Ismail

    2014-06-01

    Recent studies have shown that adult human articular cartilage contains stem-like cells within the native structure. In this study, we aimed to determine the localization of putative stem cell markers such as CD90, STRO-1, OCT-3/4, CD105 and CD166 in adult human articular cartilage tissue sections and demonstrate the expression of these markers within the expanded surface zone colony-forming (CF) cells and evaluate their differentiation potential. Biopsy samples were either fixed immediately for immunohistochemical analyses or processed for in vitro cell culture. Immunohistochemical and flow cytometry analyses were performed by using CD90, STRO-1, OCT-3/4, CD105 and CD166 antibodies. Isolated colony-forming (CF) cells were further stimulated, by using the appropriate growth factors in their pellet culture, to obtain cartilage, bone and adipose lineages. We observed that the expression of the stem cell markers were in various zones of the human adult cartilage. Flow cytometry results showed that in CF cells the expression of CD90 and CD166 was high, while OCT-3/4 was low. We also determined that CF cells could be stimulated towards cartilage, bone and adipose lineages. The results of this research support the idea that the resident stem-like cells in adult human articular cartilage express these putative stem cell markers, but further experimental investigations are needed to determine the precise localization of these cells.

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

    NASA Astrophysics Data System (ADS)

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

    2009-11-01

    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®, 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.

  16. 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

  17. 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.

  18. Development of a Valid and Reliable Knee Articular Cartilage Condition–Specific Study Methodological Quality Score

    PubMed Central

    Harris, Joshua D.; Erickson, Brandon J.; Cvetanovich, Gregory L.; Abrams, Geoffrey D.; McCormick, Frank M.; Gupta, Anil K.; Verma, Nikhil N.; Bach, Bernard R.; Cole, Brian J.

    2014-01-01

    Background: Condition-specific questionnaires are important components in evaluation of outcomes of surgical interventions. No condition-specific study methodological quality questionnaire exists for evaluation of outcomes of articular cartilage surgery in the knee. Purpose: To develop a reliable and valid knee articular cartilage–specific study methodological quality questionnaire. Study Design: Cross-sectional study. Methods: A stepwise, a priori–designed framework was created for development of a novel questionnaire. Relevant items to the topic were identified and extracted from a recent systematic review of 194 investigations of knee articular cartilage surgery. In addition, relevant items from existing generic study methodological quality questionnaires were identified. Items for a preliminary questionnaire were generated. Redundant and irrelevant items were eliminated, and acceptable items modified. The instrument was pretested and items weighed. The instrument, the MARK score (Methodological quality of ARticular cartilage studies of the Knee), was tested for validity (criterion validity) and reliability (inter- and intraobserver). Results: A 19-item, 3-domain MARK score was developed. The 100-point scale score demonstrated face validity (focus group of 8 orthopaedic surgeons) and criterion validity (strong correlation to Cochrane Quality Assessment score and Modified Coleman Methodology Score). Interobserver reliability for the overall score was good (intraclass correlation coefficient [ICC], 0.842), and for all individual items of the MARK score, acceptable to perfect (ICC, 0.70-1.000). Intraobserver reliability ICC assessed over a 3-week interval was strong for 2 reviewers (≥0.90). Conclusion: The MARK score is a valid and reliable knee articular cartilage condition–specific study methodological quality instrument. Clinical Relevance: This condition-specific questionnaire may be used to evaluate the quality of studies reporting outcomes of

  19. Genetically engineered stem cell-based strategies for articular cartilage regeneration.

    PubMed

    Santhagunam, Aruna; Madeira, Catarina; Cabral, Joaquim M S

    2012-01-01

    Cartilage is frequently injured, often as a result of inflammatory rheumatic diseases or sports-related trauma. Given its nonvascular nature, articular cartilage has a limited capability for self-repair and currently the few therapeutic options still have uncertain long-term outcomes. Cell-based surgical therapies using autologous chondrocytes to repair cartilage injury have been used in the clinic for over a decade, but this approach has shown mixed results mainly due to the low number of harvested chondrocytes and the loss of cartilage-related phenotype and functionality after several passages of in vitro culture. A wide range of cell sources have been tested to circumvent chondrocyte limitations in cartilage repair, and stem cells have been presented as those that offer the greatest potential for clinical application. This review will focus on recent advances in stem cell-based strategies for articular cartilage repair, specifically focusing on the use of genetically engineered adult stem cells by conventional gene delivery methods and by gene-activated matrices. Perspectives in cartilage engineering are also addressed.

  20. Quantitation of articular surface topography and cartilage thickness in knee joints using stereophotogrammetry.

    PubMed

    Ateshian, G A; Soslowsky, L J; Mow, V C

    1991-01-01

    An analytical stereophotogrammetry (SPG) technique has been developed based upon some of the pioneering work of Selvik [Ph.D. thesis, University of Lund, Sweden (1974)] and Huiskes and coworkers [J. Biomechanics 18, 559-570 (1985)], and represents a fundamental step in the construction of biomechanical models of diarthrodial joints. Using this technique, the precise three-dimensional topography of the cartilage surfaces of various diarthrodial joints has been obtained. The system presented in this paper delivers an accuracy of 90 microns in the least favorable conditions with 95% coverage using the same calibration method as Huiskes et al. (1985). In addition, a method has been developed, using SPG, to quantitatively map the cartilage thickness over the entire articular surface of a joint with a precision of 134 microns (95% coverage). In the present study, our SPG system has been used to quantify the topography, including surface area, of the articular surfaces of the patella, distal femur, tibial plateau, and menisci of the human knee. Furthermore, examples of cartilage thickness maps and corresponding thickness data including coefficient of variation, minimum, maximum, and mean cartilage thickness are also provided for the cartilage surfaces of the knee. These maps illustrate significant variations over the joint surfaces which are important in the determination of the stresses and strains within the cartilage during diarthrodial joint function. In addition, these cartilage surface topographies and thickness data are essential for the development of anatomically accurate finite element models of diarthrodial joints.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. 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...

  2. [Relation of ultrastructural changes of articular cartilage and the arthroscopic classification in osteoarthritic knee].

    PubMed

    Chai, B F

    1992-01-01

    This paper reported the ultrastructural changes found in the diseased articular cartilages of 43 osteoarthritic knee joints, which were assessed according to the "Arthroscopic classification of the articular cartilage". The electron microscopic findings and the arthroscopic classification of the articular lesions were correlated. The lesioned articular cartilage revealed two categories of pathological changes. 1. The changes on the part of the articular chondrocytes comprised (1) The nucleus showed pyknosis and karyorrhexis. (2) The cytoplasm exhibited fat droplets, glycogen granules, and/or microfilaments. Lysosomes also emerged frequently. The mitochondria swelled and the rough-surfaced endoplasmic reticulum dilated and became vesiculated. At the same time there was detachment of cell processes or of the cytoplasmic membrane. The chondrocyte underwent necrosis, contracted and eventually disintegrated into lipid debris. These changes increased in extent and degree with the lesion and the severity went parallel with the sequence of the "Arthroscopic stage classification". 2. The changes on the part of the matrix included appearance of electron-dense lipid debris and numerous, coarse and banded collagen fibrils. They resided both in the pericellular matrix and in the general matrix. Sometimes fibroblast-like cells made their appearance in the matrix. These cells also revealed degenerative changes. All these changes went parallel with the sequence of the "Arthroscopic grade classification".

  3. The present state of treatments for articular cartilage defects in the knee

    PubMed Central

    Perera, JR; Gikas, PD; Bentley, G

    2012-01-01

    INTRODUCTION Chondral and osteochondral lesions of the knee are notoriously difficult to treat due to the poor healing capacity of articular cartilage and the hostile environment of moving joints, ultimately causing disabling pain and early osteoarthritis. There are many different reconstructive techniques used currently but few are proven to be of value. However, some have been shown to produce a better repair with hyaline-like cartilage rather than fibrocartilage. METHODS A systematic search of all available online databases including PubMed, MEDLINE® and Embase™ was undertaken using several keywords. All the multiple treatment options and methods available were considered. These were summarised and the evidence for and against them was scrutinised. RESULTS A total of 460 articles were identified after cross-referencing the database searches using the keywords. These revealed that autologous and matrix assisted chondrocyte implantation demonstrated both ‘good to excellent’ histological results and significant improvement in clinical outcomes. CONCLUSIONS Autologous and matrix assisted chondrocyte implantation have been shown to treat symptomatic lesions successfully with significant histological and clinical improvement. There is, however, still a need for further randomised clinical trials, perfecting the type of scaffold and the use of adjuncts such as growth factors. A list of recommendations for treatment and the potential future trends of managing these lesions are given. PMID:22943326

  4. Site dependence of thickness and speed of sound in articular cartilage of bovine patella.

    PubMed

    Patil, S G; Zheng, Y P; Chen, Xin

    2010-08-01

    Researchers have made efforts to quantify thickness of articular cartilage as well as its acoustic and mechanical properties using various ultrasound (US) techniques during the last decades, because they are important indicators of articular cartilage degeneration. However, the variation of the thickness and speed of sound of articular cartilage at different anatomical sites would result in the uncertainty of US assessment of degeneration. In this paper, the site dependences of speed of sound and thickness of bovine patellar articular cartilage (n = 10) were investigated using a custom-made US measurement system. The thickness and speed of sound of articular cartilage at different locations of the bovine patella were measured on excised specimens ex situ using a noncontact US approach. A total of 10 patellae were tested. The results showed the overall mean value of the speed of sound in the articular cartilage at the 25 measured sites was 1626 +/- 86 m/s (range, 1507 to 1834 m/s). No statistically significant difference in the speed of sound was observed among the 25 locations or among the four quadrants of the patella. The highest speed of sound (1834 +/- 74 m/s) was obtained at the medial-upper quadrant and the lowest value (1507 +/- 74 m/s) at the medial-lower quadrant. Further grouping of the data revealed that the speed of sound in the central region (1633 +/- 21 m/s) was significantly (p < 0.01) larger than that for the surrounding region (1621 +/- 22 m/s). The overall mean thickness of the patellar articular cartilage was 1.34 +/- 0.34 mm. No significant difference was obtained in the thickness among the 25 locations and also among the four quadrants. However, when the thickness values were divided diagonally, a significant difference (p < 0.01) was observed between the upper region (1.27 +/- 0.11 mm) and the lower region (1.31 +/- 0.41 mm) of the patellae. Although no significant differences in the thickness and speed of sound among the tested sites were

  5. Arthroscopic optical coherence tomography provides detailed information on articular cartilage lesions in horses.

    PubMed

    te Moller, N C R; Brommer, H; Liukkonen, J; Virén, T; Timonen, M; Puhakka, P H; Jurvelin, J S; van Weeren, P R; Töyräs, J

    2013-09-01

    Arthroscopy enables direct inspection of the articular surface, but provides no information on deeper cartilage layers. Optical coherence tomography (OCT), based on measurement of reflection and backscattering of light, is a diagnostic technique used in cardiovascular surgery and ophthalmology. It provides cross-sectional images at resolutions comparable to that of low-power microscopy. The aim of this study was to determine if OCT is feasible for advanced clinical assessment of lesions in equine articular cartilage during diagnostic arthroscopy. Diagnostic arthroscopy of 36 metacarpophalangeal joints was carried out ex vivo. Of these, 18 joints with varying degrees of cartilage damage were selected, wherein OCT arthroscopy was conducted using an OCT catheter (diameter 0.9 mm) inserted through standard instrument portals. Five sites of interest, occasionally supplemented with other locations where defects were encountered, were arthroscopically graded according to the International Cartilage Repair Society (ICRS) classification system. The same sites were evaluated qualitatively (ICRS classification and morphological description of the lesions) and quantitatively (measurement of cartilage thickness) on OCT images. OCT provided high resolution images of cartilage enabling determination of cartilage thickness. Comparing ICRS grades determined by both arthroscopy and OCT revealed poor agreement. Furthermore, OCT visualised a spectrum of lesions, including cavitation, fibrillation, superficial and deep clefts, erosion, ulceration and fragmentation. In addition, with OCT the arthroscopically inaccessible area between the dorsal MC3 and P1 was reachable in some cases. Arthroscopically-guided OCT provided more detailed and quantitative information on the morphology of articular cartilage lesions than conventional arthroscopy. OCT could therefore improve the diagnostic value of arthroscopy in equine orthopaedic surgery.

  6. UTE bi-component analysis of T2* relaxation in articular cartilage

    PubMed Central

    Shao, H.; Chang, E.Y.; Pauli, C.; Zanganeh, S.; Bae, W.; Chung, C.B.; Tang, G.; Du, J.

    2015-01-01

    SUMMARY Objectives To determine T2* relaxation in articular cartilage using ultrashort echo time (UTE) imaging and bi-component analysis, with an emphasis on the deep radial and calcified cartilage. Methods Ten patellar samples were imaged using two-dimensional (2D) UTE and Car-Purcell-Meiboom-Gill (CPMG) sequences. UTE images were fitted with a bi-component model to calculate T2* and relative fractions. CPMG images were fitted with a single-component model to calculate T2. The high signal line above the subchondral bone was regarded as the deep radial and calcified cartilage. Depth and orientation dependence of T2*, fraction and T2 were analyzed with histopathology and polarized light microscopy (PLM), confirming normal regions of articular cartilage. An interleaved multi-echo UTE acquisition scheme was proposed for in vivo applications (n = 5). Results The short T2* values remained relatively constant across the cartilage depth while the long T2* values and long T2* fractions tended to increase from subchondral bone to the superficial cartilage. Long T2*s and T2s showed significant magic angle effect for all layers of cartilage from the medial to lateral facets, while the short T2* values and T2* fractions are insensitive to the magic angle effect. The deep radial and calcified cartilage showed a mean short T2* of 0.80 ± 0.05 ms and short T2* fraction of 39.93 ± 3.05% in vitro, and a mean short T2* of 0.93 ± 0.58 ms and short T2* fraction of 35.03 ± 4.09% in vivo. Conclusion UTE bi-component analysis can characterize the short and long T2* values and fractions across the cartilage depth, including the deep radial and calcified cartilage. The short T2* values and T2* fractions are magic angle insensitive. PMID:26382110

  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. Enhancing chondrogenic phenotype for cartilage tissue engineering: monoculture and coculture of articular chondrocytes and mesenchymal stem cells.

    PubMed

    Hubka, Kelsea M; Dahlin, Rebecca L; Meretoja, Ville V; Kasper, F Kurtis; Mikos, Antonios G

    2014-12-01

    Articular cartilage exhibits an inherently low rate of regeneration. Consequently, damage to articular cartilage often requires surgical intervention. However, existing treatments generally result in the formation of fibrocartilage tissue, which is inferior to native articular cartilage. As a result, cartilage engineering strategies seek to repair or replace damaged cartilage with an engineered tissue that restores full functionality to the impaired joint. These strategies often involve the use of chondrocytes, yet in vitro expansion and culture can lead to undesirable changes in chondrocyte phenotype. This review focuses on the use of articular chondrocytes and mesenchymal stem cells (MSCs) in either monoculture or coculture for the enhancement of chondrogenesis. Coculture strategies increasingly outperform their monoculture counterparts with regard to chondrogenesis and present unique opportunities to attain chondrocyte phenotype stability in vitro. Methods to prevent chondrocyte dedifferentiation and promote chondrocyte redifferentiation as well as to promote the chondrogenic differentiation of MSCs while preventing MSC hypertrophy are discussed.

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

    NASA Astrophysics Data System (ADS)

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

    2007-03-01

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

  10. A new pressure chamber to study the biosynthetic response of articular cartilage to mechanical loading.

    PubMed

    Steinmeyer, J; Torzilli, P A; Burton-Wurster, N; Lust, G

    1993-01-01

    A prototype chamber was used to apply a precise cyclic or static load on articular cartilage explants under sterile conditions. A variable pressure, pneumatic controller was constructed to power the chamber's air cylinder, capable of applying, with a porous load platen, loads of up to 10 MPa at cycles ranging from 0 to 10 Hz. Pig articular cartilage explants were maintained successfully in this chamber for 2 days under cyclic mechanical loading of 0.5 Hz, 0.5 MPa. Explants remained sterile, viable and metabolically active. Cartilage responded to this load with a decreased synthesis of fibronectin and a small but statistically significant elevation in proteoglycan content. Similar but less extensive effects on fibronectin synthesis were observed with the small static load (0.016 MPa) inherent in the design of the chamber.

  11. Identification of stable normalization genes for quantitative real-time PCR in porcine articular cartilage

    PubMed Central

    2012-01-01

    Background Expression levels for genes of interest must be normalized with an appropriate reference, or housekeeping gene, to make accurate comparisons of quantitative real-time PCR results. The purpose of this study was to identify the most stable housekeeping genes in porcine articular cartilage subjected to a mechanical injury from a panel of 10 candidate genes. Results Ten candidate housekeeping genes were evaluated in three different treatment groups of mechanically impacted porcine articular cartilage. The genes evaluated were: beta actin, beta-2-microglobulin, glyceraldehyde-3-phosphate dehydrogenase, hydroxymethylbilane synthase, hypoxanthine phosphoribosyl transferase, peptidylprolyl isomerase A (cyclophilin A), ribosomal protein L4, succinate dehydrogenase flavoprotein subunit A, TATA box binding protein, and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein—zeta polypeptide. The stability of the genes was measured using geNorm, BestKeeper, and NormFinder software. The four most stable genes measured via geNorm were (most to least stable) succinate dehydrogenase flavoprotein, subunit A, peptidylprolyl isomerase A, glyceraldehyde-3-phosphate dehydrogenase, beta actin; the four most stable genes measured via BestKeeper were glyceraldehyde-3-phosphate dehydrogenase, peptidylprolyl isomerase A, beta actin, succinate dehydrogenase flavoprotein, subunit A; and the four most stable genes measured via NormFinder were peptidylprolyl isomerase A, succinate dehydrogenase flavoprotein, subunit A, glyceraldehyde-3-phosphate dehydrogenase, beta actin. Conclusions BestKeeper, geNorm, and NormFinder all generated similar results for the most stable genes in porcine articular cartilage. The use of these appropriate reference genes will facilitate accurate gene expression studies of porcine articular cartilage and suggest appropriate housekeeping genes for articular cartilage studies in other species. PMID:23146128

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

    PubMed

    Alibardi, Lorenzo

    2015-09-01

    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.

  14. Electromechanical probe and automated indentation maps are sensitive techniques in assessing early degenerated human articular cartilage.

    PubMed

    Sim, Sotcheadt; Chevrier, Anik; Garon, Martin; Quenneville, Eric; Lavigne, Patrick; Yaroshinsky, Alex; Hoemann, Caroline D; Buschmann, Michael D

    2016-06-09

    Recent advances in the development of new drugs to halt or even reverse the progression of Osteoarthritis at an early-stage requires new tools to detect early degeneration of articular cartilage. We investigated the ability of an electromechanical probe and an automated indentation technique to characterize entire human articular surfaces for rapid non-destructive discrimination between early degenerated and healthy articular cartilage. Human cadaveric asymptomatic articular surfaces (4 pairs of distal femurs and 4 pairs of tibial plateaus) were used. They were assessed ex vivo: macroscopically, electromechanically (maps of the electromechanical quantitative parameter, QP, reflecting streaming potentials), mechanically (maps of the instantaneous modulus, IM) and through cartilage thickness. Osteochondral cores were also harvested from healthy and degenerated regions for histological assessment, biochemical analyses and unconfined compression tests. The macroscopic visual assessment delimited three distinct regions on each articular surface: region I was macroscopically degenerated, region II was macroscopically normal but adjacent to region I and region III was the remaining normal articular surface. Thus, each extracted core was assigned to one of the three regions. A mixed effect model revealed that only the QP (p < 0.0001) and IM (p < 0.0001) were able to statistically discriminate the three regions. Effect size was higher for QP and IM than other assessments, indicating greater sensitivity to distinguish early degeneration of cartilage. When considering the mapping feature of the QP and IM techniques, it also revealed bilateral symmetry in a moderately similar distribution pattern between bilateral joints. This article is protected by copyright. All rights reserved.

  15. Collagen fibre arrangement in the tibial plateau articular cartilage of man and other mammalian species

    PubMed Central

    KÄÄB, M. J.; AP GWYNN, I.; NÖTZLI, H. P.

    1998-01-01

    Experimental animal models are frequently used to study articular cartilage, but the relevance to man remains problematic. In this study animal models were compared by examination of the collagen fibre arrangement in the medial tibial plateau of human, cow, pig, dog, sheep, rabbit and rat specimens. 24 cartilage samples from each species were prepared and maximum cartilage thickness in the central tibial plateau measured. Samples were fixed, dehydrated, freeze-fractured and imaged by scanning electron microscopy (SEM). At low magnification, 2 different arrangements of collagen fibres were observed: leaf-like (human, pig, dog) and columnar (cow, sheep, rabbit, rat). The porcine collagen structure was the most similar to that of man. This arrangement was consistent from the radial to the upper zones. Under higher magnification at the surface of the leaves, the collagen was more randomly oriented, whereas the columns consisted of parallel collagen fibrils. The maximum thickness of cartilage did not correlate with the type of collagen arrangement but was correlated with the body weight of the species (r=0.785). When using animal models for investigating human articular cartilage function or pathology, the differences in arrangement of collagen fibres in tibial plateau cartilage between laboratory animals should be considered especially if morphological evaluation is planned. PMID:9758134

  16. The role of lubricant entrapment at biological interfaces: reduction of friction and adhesion in articular cartilage.

    PubMed

    Chan, S M T; Neu, C P; Komvopoulos, K; Reddi, A H

    2011-07-28

    Friction and adhesion of articular cartilage from high- and low-load-bearing regions of bovine knee joints were examined with a tribometer under various loads and equilibration times. The effect of trapped lubricants was investigated by briefly unloading the cartilage sample before friction testing, to allow fluid to reflow into the contact interface and boundary lubricants to rearrange. Friction and adhesion of high-load-bearing joint regions were consistently lower than those of low-load-bearing regions. This investigation is the first to demonstrate the regional variation in the friction and adhesion properties of articular cartilage. Friction coefficient decreased with increasing contact pressure and decreasing equilibration time. Briefly unloading cartilage before the onset of sliding resulted in significantly lower friction and adhesion and a loss of the friction dependence on contact pressure, suggesting an enhancement of the cartilage tribological properties by trapped lubricants. The results of this study reveal significant differences in the friction and adhesion properties between high- and low-load-bearing joint regions and elucidate the role of trapped lubricants in cartilage tribology.

  17. 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

  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. Application of multiphysics models to efficient design of experiments of solute transport across articular cartilage.

    PubMed

    Pouran, Behdad; Arbabi, Vahid; Weinans, Harrie; Zadpoor, Amir A

    2016-11-01

    Transport of solutes helps to regulate normal physiology and proper function of cartilage in diarthrodial joints. Multiple studies have shown the effects of characteristic parameters such as concentration of proteoglycans and collagens and the orientation of collagen fibrils on the diffusion process. However, not much quantitative information and accurate models are available to help understand how the characteristics of the fluid surrounding articular cartilage influence the diffusion process. In this study, we used a combination of micro-computed tomography experiments and biphasic-solute finite element models to study the effects of three parameters of the overlying bath on the diffusion of neutral solutes across cartilage zones. Those parameters include bath size, degree of stirring of the bath, and the size and concentration of the stagnant layer that forms at the interface of cartilage and bath. Parametric studies determined the minimum of the finite bath size for which the diffusion behavior reduces to that of an infinite bath. Stirring of the bath proved to remarkably influence neutral solute transport across cartilage zones. The well-stirred condition was achieved only when the ratio of the diffusivity of bath to that of cartilage was greater than ≈1000. While the thickness of the stagnant layer at the cartilage-bath interface did not significantly influence the diffusion behavior, increase in its concentration substantially elevated solute concentration in cartilage. Sufficient stirring attenuated the effects of the stagnant layer. Our findings could be used for efficient design of experimental protocols aimed at understanding the transport of molecules across articular cartilage.

  20. Topographical mapping of biochemical properties of articular cartilage in the equine fetlock joint.

    PubMed

    Brama, P A; Tekoppele, J M; Bank, R A; Karssenberg, D; Barneveld, A; van Weeren, P R

    2000-01-01

    The aim of this study was to evaluate topographical differences in the biochemical composition of the extracellular matrix of articular cartilage of the normal equine fetlock joint. Water content, DNA content, glycosaminoglycan (GAG) content and a number of characteristics of the collagen network (total collagen content, levels of hydroxylysine- (Hyl) and the crosslink hydroxylysylpyridinoline, (HP) of articular cartilage in the proximal 1st phalanx (P1), distal 3rd metacarpal bone (MC), and proximal sesamoid bones (PSB) were determined in the left and right fetlock joint of 6 mature horses (age 5-9 years). Twenty-eight sites were sampled per joint, which included the clinically important areas often associated with pathology. Biochemical differences were evaluated between sampling sites and related with the predisposition for osteochondral injury and type of loading. Significant regional differences in the composition of the extracellular matrix existed within the joint. Furthermore, left and right joints exhibited biochemical differences. Typical topographic distribution patterns were observed for each parameter. In P1 the dorsal and palmar articular margin showed a significantly lower GAG content than the more centrally located sites. Collagen content and HP crosslinks were higher at the joint margins than in the central area. Also, in the MC, GAG content was significantly lower at the (dorsal) articular margin compared with the central area. Consistent with findings in P1, collagen and HP crosslinks were significantly lower in the central area compared to the (dorsal) articular margin. Biochemical and biomechanical heterogeneity of articular cartilage is supposed to reflect the different functional demands made at different sites. In the present study, GAG content was highest in the constantly loaded central areas of the joint surfaces. In contrast, collagen content and HP crosslinks were higher in areas intermittently subjected to peak loading which suggests

  1. Inhibition of articular cartilage degradation by glucosamine-HCl and chondroitin sulphate.

    PubMed

    Orth, M W; Peters, T L; Hawkins, J N

    2002-09-01

    Glucosamine and chondroitin sulphate in many animal and human trials has improved joint health. In vitro studies are beginning to clarify their mode of action. The objective of this research was to: 1) determine at what concentrations glucosamine-HCl (GLN) and/or chondroitin sulphate (CS) would inhibit the cytokine-induced catabolic response in equine articular cartilage explants and 2) to determine if a combination of the 2 was more effective at inhibiting the catabolic response than the individual compounds. Articular cartilage was obtained from carpal joints of horses (age 1-4 years). Cartilage discs (3.5 mm) were biopsied and cultured. Explants were incubated with lipopolysaccharide (LPS) in the presence of varying concentrations of GLN, CS, or both. Control treatments included explants with no LPS and LPS without GLN or CS. Media were analysed for nitric oxide (NO), prostaglandin E2 (PGE2) and keratan sulphate. Cartilage was extracted for analysis of metalloproteinases (MMP). Four experiments were conducted. In all experiments, GLN at concentrations as low as 1 mg/ml decreased NO production relative to LPS stimulated cartilage without GLN over the 4 day period. In general, CS at either 0.25 or 0.5 mg/ml did not inhibit NO production. The addition of CS to GLN containing media did not further inhibit NO production. GLN at concentrations as low as 0.5 mg/ml decreased PGE2 production, whereas CS did not effect on PGE2. The combination of GLN/CS decreased MMP-9 gelatinolytic activity but had no effect on MMP-2 activity. The combination in 2 experiments tended to decrease MMP-13 protein concentrations and decreased keratan sulphate levels in media. Overall, the combination of GLN (1 mg/ml) and CS (0.25 mg/ml) inhibited the synthesis of several mediators of cartilage degradation. These results further support the effort to understand the role of GLN and CS in preserving articular cartilage in athletic horses.

  2. Boundary mode lubrication of articular cartilage by recombinant human lubricin.

    PubMed

    Gleghorn, Jason P; Jones, Aled R C; Flannery, Carl R; Bonassar, Lawrence J

    2009-06-01

    Lubrication of cartilage involves a variety of physical and chemical factors, including lubricin, a synovial glycoprotein that has been shown to be a boundary lubricant. It is unclear how lubricin boundary lubricates a wide range of bearings from tissue to artificial surfaces, and if the mechanism is the same for both soluble and bound lubricin. In the current study, experiments were conducted to investigate the hypothesis that recombinant human lubricin (rh-lubricin) lubricates cartilage in a dose-dependent manner and that soluble and bound fractions of rh-lubricin both contribute to the lubrication process. An rh-lubricin dose response was observed with maximal lubrication achieved at concentrations of rh-lubricin greater than 50 microg/mL. A concentration-response variable-slope model was fit to the data, and indicated that rh-lubricin binding to cartilage was not first order. The pattern of decrease in equilibrium friction coefficient indicated that aggregation of rh-lubricin or steric arrangement may regulate boundary lubrication. rh-lubricin localized at the cartilage surface was found to lubricate a cartilage-glass interface in boundary mode, as did soluble rh-lubricin at high concentrations (150 microg/mL); however, the most effective lubrication occurred when both soluble and bound rh-lubricin were present at the interface. These findings point to two distinct mechanisms by which rh-lubricin lubricates, one mechanism involving lubricin bound to the tissue surface and the other involving lubricin in solution.

  3. 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.

  4. Intra-articular hyaluronic acid increases cartilage breakdown biomarker in patients with knee osteoarthritis.

    PubMed

    Gonzalez-Fuentes, Alexandra M; Green, David M; Rossen, Roger D; Ng, Bernard

    2010-06-01

    Intra-articular hyaluronic acid has been used in treatment of patients with knee osteoarthritis. Though its effect on pain has been well studied, it is not clear how it affects the articular cartilage. This is a preliminary study to evaluate the kinetics of urinary collagen type-II C-telopeptide (CTX-II) as a biomarker of collagen breakdown in response to intra-articular hyaluronic acid injection in patients with symptomatic knee osteoarthritis. Intra-articular injections of hyaluronan were administered to ten patients with symptomatic knee osteoarthritis. Urine collection for urinary CTX-II was obtained at baseline, before each injection and once every other week for a total of 6 months. Urine CTX-II was measured using a CartiLaps(c) ELISA kit. There was a statistically significant increase (p = 0.0136) in CTX-II a week after the third intra-articular injection of hyaluronic acid (6,216 ng/mmol +/- 4,428) compared with baseline (2,233 ng/mmol +/- 1,220). This increase in CTX-II was sustained throughout the entire 6 months follow-up period (repeated measures ANOVA, p < 0.015). This is the first study of changes in an osteoarthritis biomarker after intra-articular hyaluronic acid injections in patients with symptomatic knee osteoarthritis. Contrary to our initial hypothesis that CTX-II levels should decrease after intra-articular hyaluronic acid injections, we found a significant increase in urinary CTX-II levels that was sustained throughout the study. These observations suggest that intra-articular hyaluronic acid injections may accelerate cartilage breakdown in patients with symptomatic knee osteoarthritis. The responsible mechanisms are unknown and warrant further study.

  5. 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.

  6. Keratan sulfate as a marker of articular cartilage catabolism and joint treatment in ponies.

    PubMed

    Todhunter, R J; Yeager, A E; Freeman, K P; Parente, E J; Lust, G

    1993-07-01

    Keratan sulfate (KS) is a glycosaminoglycan, distribution of which is confined mostly to hyaline cartilage. As such, it is a putative marker of hyaline cartilage catabolism. In experiment 1, a focal osteochondral defect was made arthroscopically in 1 radial carpal bone of 2 ponies, and in 2 other ponies, chymopapain was injected into the radiocarpal joint to induce cartilage catabolism. Sequential and concurrent plasma and synovial fluid concentrations of KS were measured, up to 13 months after induction of cartilage injury, to determine whether changes in KS concentrations reflected cartilage catabolism. In experiment 2, a large, bilateral osteochondral defect was made in the radial carpal bones of 18 ponies, which were subsequently given postoperative exercise and/or injected intra-articularly with 250 mg of polysulfated glycosaminoglycan (PSGAG). Medication was given at surgery, then weekly for 4 weeks. Blood samples were collected and synovial fluid was aspirated before surgery, when medication was given, and at postmortem examination (postoperative week 17). The KS concentration was measured in these fluids to determine whether changes in KS concentration indicated an effect of joint treatment. In experiment 1, the concentration of KS in synovial fluid was highest 1 day after joint injury, and the concentration in plasma peaked 2 days after joint injury. For ponies receiving chymopapain intra-articularly (generalized cartilage catabolism), a fivefold increase over baseline was observed in the concentration of KS in plasma (peak mean, 1.2 micrograms/ml), and a tenfold increase over baseline in synovial fluid (peak mean, 2.0 mg/ml) was observed. On average, these maxima were threefold higher than values in fluids of ponies with osteochondral defects (focal cartilage disease). In experiment 2, nonexercised ponies had lower KS concentration (as a percentage of the preoperative concentration) in synovial fluid than did exercised ponies at all postoperative times

  7. A finite element exploration of cartilage stress near an articular incongruity during unstable motion.

    PubMed

    Goreham-Voss, Curtis M; McKinley, Todd O; Brown, Thomas D

    2007-01-01

    Both instability and residual articular incongruity are implicated in the development of post-traumatic osteoarthritis (OA) following intra-articular fracture, but currently no information exists regarding cartilage stresses for unstable residual incongruities. In this study, a transversely isotropic poroelastic cartilage finite element model was implemented and validated within physiologically relevant loading ranges. This material model was then used to simulate the loading of cartilage during stable and unstable motion accompanying a step-off incongruity residual from intra-articular fracture, using load data from previous cadaver tests of ankle instability. Peak solid-phase stresses and fluid pressure were found to increase markedly in the presence of instability. Solid-phase transients of normal stress increased from 2.00 to 13.8 MPa/s for stable compared to unstable motion, and tangential stress transients increased from 17.1 to 118.1 MPa/s. Corresponding fluid pressure transients increased from 15.1 to 117.9 MPa/s for unstable motion. In the most rapidly loaded sections of cartilage, the fluid was found to carry nearly all of the normal load, with the pressurization of the fluid resulting in high solid matrix tangential stresses.

  8. 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.

  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.

  10. Effect of anti-inflammatory drugs on sulphated glycosaminoglycan synthesis in aged human articular cartilage.

    PubMed Central

    McKenzie, L S; Horsburgh, B A; Ghosh, P; Taylor, T K

    1976-01-01

    The anti-inflammatory drugs, sodium salicylate, indomethacin, hydrocortisone, ibuprofen, and flurbiprofen, were examined for their effects on sulphated glycosaminoglycan synthesis in aged human cartilage in vitro. Cartilage was obtained from femoral heads removed during surgery and drug effects were found to vary significantly from one head to another. Statistical analysis of the results showed that sodium salicylate exhibits concentration-dependent inhibition of glycosaminoglycan synthesis over the concentration range used. Indomethacin, hydrocortisone, and ibuprofen, at concentrations comparable to those attained in man, caused a statistically significant depression of sulphated glycosaminoglycan synthesis in cartilage from some femoral heads but not others, reflecting the variable response of human articular cartilage to anti-inflammatory drugs. Sodium salicylate and indomethacin at higher doses produced significant (Pless than 0-005) inhibition of sulphated glycosaminoglycan synthesis in all femoral heads studied. The results for flurbiprofen were less conclusive; this compound appears not to inhibit glycosaminoglycan synthesis over the concentration range used. PMID:1008617

  11. 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.

  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. Effects of Fiber Orientation on the Frictional Properties and Damage of Regenerative Articular Cartilage Surfaces

    PubMed Central

    Accardi, Mario Alberto; McCullen, Seth D.; Callanan, Anthony; Chung, Sangwon; Cann, Philippa M.

    2013-01-01

    Articular cartilage provides a low-friction, wear-resistant surface for diarthrodial joints. Due to overloading and overuse, articular cartilage is known to undergo significant wear and degeneration potentially resulting in osteoarthritis (OA). Regenerative medicine strategies offer a promising solution for the treatment of articular cartilage defects and potentially localized early OA. Such strategies rely on the development of materials to restore some aspects of cartilage. In this study, microfibrous poly(ɛ-caprolactone) scaffolds of varying fiber orientations (random and aligned) were cultured with bovine chondrocytes for 4 weeks in vitro, and the mechanical and frictional properties were evaluated. Mechanical properties were quantified using unconfined compression and tensile testing techniques. Frictional properties were investigated at physiological compressive strains occurring in native articular cartilage. Scaffolds were sheared along the fiber direction, perpendicular to the fiber direction and in random orientation. The evolution of damage as a result of shear was evaluated via white light interferometry and scanning electron microscopy. As expected, the fiber orientation strongly affected the tensile properties as well as the compressive modulus of the scaffolds. Fiber orientation did not significantly affect the equilibrium frictional coefficient, but it was, however, a key factor in dictating the evolution of surface damage on the surface. Scaffolds shear tested perpendicular to the fiber orientation displayed the highest surface damage. Our results suggest that the fiber orientation of the scaffold implanted in the joint could strongly affect its resistance to damage due to shear. Scaffold fiber orientation should thus be carefully considered when using microfibrous scaffolds. PMID:23688110

  14. Decellularization of porcine articular cartilage explants and their subsequent repopulation with human chondroprogenitor cells.

    PubMed

    Luo, Lu; Eswaramoorthy, Rajalakshmanan; Mulhall, Kevin J; Kelly, Daniel J

    2015-03-01

    Engineering tissues with comparable structure, composition and mechanical functionality to native articular cartilage remains a challenge. One possible solution would be to decellularize xenogeneic articular cartilage in such a way that the structure of the tissue is maintained, and to then repopulate this decellularized matrix with human chondroprogenitor cells that will facilitate the reconstitution, maintenance and eventual turnover of the construct following implantation. The overall objective of this study was to develop a protocol to efficiently decellularize porcine articular cartilage grafts and to identify a methodology to subsequently repopulate such explants with human chondroprogenitor cells. To this end, channels were first introduced into cylindrical articular cartilage explants, which were then decellularized with a combination of various chemical reagents including sodium dodecyl sulfate (SDS) and nucleases. The decellularization protocol resulted in a ~90% reduction in porcine DNA content, with little observed effect on the collagen content and the collagen architecture of the tissue, although a near-complete removal of sulfated glycosaminoglycans (sGAG) and a related reduction in tissue compressive properties was observed. The introduction of channels did not have any detrimental effect on the biochemical or the mechanical properties of the decellularized tissue. Next, decellularized cartilage explants with or without channels were seeded with human infrapatellar fat pad derived stem cells (FPSCs) and cultured chondrogenically under either static or rotational conditions for 10 days. Both channeled and non-channeled explants supported the viability, proliferation and chondrogenic differentiation of FPSCs. The addition of channels facilitated cell migration and subsequent deposition of cartilage-specific matrix into more central regions of these explants. The application of rotational culture appeared to promote a less proliferative cellular

  15. 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.

  16. Epidemiology and imaging of the subchondral bone in articular cartilage repair.

    PubMed

    Menetrey, Jacques; Unno-Veith, Florence; Madry, Henning; Van Breuseghem, Iwan

    2010-04-01

    Articular cartilage and the subchondral bone act as a functional unit. Following trauma, osteochondritis dissecans, osteonecrosis or osteoarthritis, this intimate connection may become disrupted. Osteochondral defects-the type of defects that extend into the subchondral bone-account for about 5% of all articular cartilage lesions. They are very often caused by trauma, in about one-third of the cases by osteoarthritis and rarely by osteochondritis dissecans. Osteochondral defects are predominantly located on the medial femoral condyle and also on the patella. Frequently, they are associated with lesions of the menisci or the anterior cruciate ligament. Because of the close relationship between the articular cartilage and the subchondral bone, imaging of cartilage defects or cartilage repair should also focus on the subchondral bone. Magnetic resonance imaging is currently considered to be the key modality for the evaluation of cartilage and underlying subchondral bone. However, the choice of imaging technique also depends on the nature of the disease that caused the subchondral bone lesion. For example, radiography is still the golden standard for imaging features of osteoarthritis. Bone scintigraphy is one of the most valuable techniques for early diagnosis of spontaneous osteonecrosis about the knee. A CT scan is a useful technique to rule out a possible depression of the subchondral bone plate, whereas a CT arthrography is highly accurate to evaluate the stability of the osteochondral fragment in osteochondritis dissecans. Particularly for the problem of subchondral bone lesions, image evaluation methods need to be refined for adequate and reproducible analysis. This article highlights recent studies on the epidemiology and imaging of the subchondral bone, with an emphasis on magnetic resonance imaging.

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

    PubMed

    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 Vz,t technique. Vz,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 Vz,t data to reconstruct the 2D reflection spectrum Rθ,ω. To obtain the reflection coefficient of articular cartilage, the Vz,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. Helium ion microscopy for high-resolution visualization of the articular cartilage collagen network.

    PubMed

    Vanden Berg-Foels, W S; Scipioni, L; Huynh, C; Wen, X

    2012-05-01

    The articular cartilage collagen network is an important research focus because network disruption results in cartilage degeneration and patient disability. The recently introduced helium ion microscope (HIM), with its smaller probe size, longer depth of field and charge neutralization, has the potential to overcome the inherent limitations of electron microscopy for visualization of collagen network features, particularly at the nanoscale. In this study, we evaluated the capabilities of the helium ion microscope for high-resolution visualization of the articular cartilage collagen network. Images of rabbit knee cartilage were acquired with a helium ion microscope; comparison images were acquired with a field emission scanning electron microscope (FE-SEM) and a transmission electron microscope (TEM). Sharpness of example high-resolution helium ion microscope and field emission scanning electron microscope images was quantified using the 25-75% rise distance metric. The helium ion microscope was able to acquire high-resolution images with unprecedented clarity, with greater sharpness and three-dimensional-like detail of nanoscale fibril morphologies and fibril connections, in samples without conductive coatings. These nanoscale features could not be resolved by field emission scanning electron microscopy, and three-dimensional network structure could not be visualized with transmission electron microscopy. The nanoscale three-dimensional-like visualization capabilities of the helium ion microscope will enable new avenues of investigation in cartilage collagen network research.

  19. 3-D segmentation of articular cartilages by graph cuts using knee MR images from osteoarthritis initiative

    NASA Astrophysics Data System (ADS)

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

    2008-03-01

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

  20. 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.

  1. Quantification of the optical surface reflection and surface roughness of articular cartilage using optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Saarakkala, Simo; Wang, Shu-Zhe; Huang, Yan-Ping; Zheng, Yong-Ping

    2009-11-01

    Optical coherence tomography (OCT) is a promising new technique for characterizing the structural changes of articular cartilage in osteoarthritis (OA). The calculation of quantitative parameters from the OCT signal is an important step to develop OCT as an effective diagnostic technique. In this study, two novel parameters for the quantification of optical surface reflection and surface roughness from OCT measurements are introduced: optical surface reflection coefficient (ORC), describing the amount of a ratio of the optical reflection from cartilage surface with respect to that from a reference material, and OCT roughness index (ORI) indicating the smoothness of the cartilage surface. The sensitivity of ORC and ORI to detect changes in bovine articular cartilage samples after enzymatic degradations of collagen and proteoglycans using collagenase and trypsin enzymes, respectively, was tested in vitro. A significant decrease (p < 0.001) in ORC as well as a significant increase (p < 0.001) in ORI was observed after collagenase digestion. After trypsin digestion, no significant changes in ORC or ORI were observed. To conclude, the new parameters introduced were demonstrated to be feasible and sensitive to detect typical OA-like degenerative changes in the collagen network. From the clinical point of view, the quantification of OCT measurements is of great interest since OCT probes have been already miniaturized and applied in patient studies during arthroscopy or open knee surgery in vivo. Further studies are still necessary to demonstrate the clinical capability of the introduced parameters for naturally occurring early OA changes in the cartilage.

  2. Repair of articular cartilage defects by tissue-engineered cartilage constructed with adipose-derived stem cells and acellular cartilaginous matrix in rabbits.

    PubMed

    Wang, Z J; An, R Z; Zhao, J Y; Zhang, Q; Yang, J; Wang, J B; Wen, G Y; Yuan, X H; Qi, X W; Li, S J; Ye, X C

    2014-06-18

    After injury, inflammation, or degeneration, articular cartilage has limited self-repair ability. We aimed to explore the feasibility of repair of articular cartilage defects with tissue-engineered cartilage constructed by acellular cartilage matrices (ACMs) seeded with adipose-derived stem cells (ADSCs). The ADSCs were isolated from 3-month-old New Zealand albino rabbit by using collagenase and cultured and amplified in vitro. Fresh cartilage isolated from adult New Zealand albino rabbit were freeze-dried for 12 h and treated with Triton X-100, DNase, and RNase to obtain ACMs. ADSCs were seeded in the acellular cartilaginous matrix at 2x10(7)/mL, and cultured in chondrogenic differentiation medium for 2 weeks to construct tissue-engineered cartilage. Twenty-four New Zealand white rabbits were randomly divided into A, B, and C groups. Engineered cartilage was transplanted into cartilage defect position of rabbits in group A, group B obtained ACMs, and group C did not receive any transplants. The rabbits were sacrificed in week 12. The restored tissue was evaluated using macroscopy, histology, immunohistochemistry, and transmission electron microscopy (TEM). In the tissue-engineered cartilage group (group A), articular cartilage defects of the rabbits were filled with chondrocyte-like tissue with smooth surface. Immunohistochemistry showed type II-collagen expression and Alcian blue staining was positive. TEM showed chondrocytes in the recesses, with plenty of secretary matrix particles. In the scaffold group (group B), the defect was filled with fibrous tissue. No repaired tissue was found in the blank group (group C). Tissue-engineered cartilage using ACM seeded with ADSCs can help repair articular cartilage defects in rabbits.

  3. 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.

  4. A biomechanical triphasic approach to the transport of nondilute solutions in articular cartilage.

    PubMed

    Abazari, Alireza; Elliott, Janet A W; Law, Garson K; McGann, Locksley E; Jomha, Nadr M

    2009-12-16

    Biomechanical models for biological tissues such as articular cartilage generally contain an ideal, dilute solution assumption. In this article, a biomechanical triphasic model of cartilage is described that includes nondilute treatment of concentrated solutions such as those applied in vitrification of biological tissues. The chemical potential equations of the triphasic model are modified and the transport equations are adjusted for the volume fraction and frictional coefficients of the solutes that are not negligible in such solutions. Four transport parameters, i.e., water permeability, solute permeability, diffusion coefficient of solute in solvent within the cartilage, and the cartilage stiffness modulus, are defined as four degrees of freedom for the model. Water and solute transport in cartilage were simulated using the model and predictions of average concentration increase and cartilage weight were fit to experimental data to obtain the values of the four transport parameters. As far as we know, this is the first study to formulate the solvent and solute transport equations of nondilute solutions in the cartilage matrix. It is shown that the values obtained for the transport parameters are within the ranges reported in the available literature, which confirms the proposed model approach.

  5. The Rigid Curette Technique for the Application of Fibrin Bioadhesive During Hip Arthroscopy for Articular Cartilage Lesions

    PubMed Central

    Asopa, Vipin; Singh, Parminder J.

    2014-01-01

    Encouraging midterm results have recently been reported for the arthroscopic treatment of delaminating articular cartilage lesions at the capsulolabral junction of the hip joint using fibrin bioadhesive. The needle used to introduce the bioadhesive is long, flexible, and often difficult to position. We describe a novel technique for introducing the needle that allows accurate placement behind the delaminated articular cartilage pocket during hip arthroscopy. PMID:24904770

  6. Effect of low-level helium-neon laser therapy on histological and ultrastructural features of immobilized rabbit articular cartilage.

    PubMed

    Bayat, Mohammad; Ansari, Enayatallah; Gholami, Narges; Bayat, Aghdas

    2007-05-25

    The present study investigates whether low-level helium-neon laser therapy can increase histological parameters of immobilized articular cartilage in rabbits or not. Twenty five rabbits were divided into three groups: the experiment group, which received low-level helium-neon laser therapy with 13J/cm(2) three times a week after immobilization of their right knees; the control group which did not receive laser therapy after immobilization of their knees; and the normal group which received neither immobilization nor laser therapy. Histological and electron microscopic examinations were performed at 4 and 7 weeks after immobilization. Depth of the chondrocyte filopodia in four-week immobilized experiment group, and depth of articular cartilage in seven-week immobilized experiment group were significantly higher than those of relevant control groups (exact Fisher test, p=0.001; student's t-test, p=0.031, respectively). The surfaces of articular cartilages of the experiment group were relatively smooth, while those of the control group were unsmooth. It is therefore concluded that low-level helium-neon laser therapy had significantly increased the depth of the chondrocyte filopodia in four-week immobilized femoral articular cartilage and the depth of articular cartilage in seven-week immobilized knee in comparison with control immobilized articular cartilage.

  7. 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.

  8. High-resolution measurements of the multilayer ultra-structure of articular cartilage and their translational potential

    PubMed Central

    2014-01-01

    Current musculoskeletal imaging techniques usually target the macro-morphology of articular cartilage or use histological analysis. These techniques are able to reveal advanced osteoarthritic changes in articular cartilage but fail to give detailed information to distinguish early osteoarthritis from healthy cartilage, and this necessitates high-resolution imaging techniques measuring cells and the extracellular matrix within the multilayer structure of articular cartilage. This review provides a comprehensive exploration of the cellular components and extracellular matrix of articular cartilage as well as high-resolution imaging techniques, including magnetic resonance image, electron microscopy, confocal laser scanning microscopy, second harmonic generation microscopy, and laser scanning confocal arthroscopy, in the measurement of multilayer ultra-structures of articular cartilage. This review also provides an overview for micro-structural analysis of the main components of normal or osteoarthritic cartilage and discusses the potential and challenges associated with developing non-invasive high-resolution imaging techniques for both research and clinical diagnosis of early to late osteoarthritis. PMID:24946278

  9. VDIPEN, a metalloproteinase-generated neoepitope, is induced and immunolocalized in articular cartilage during inflammatory arthritis.

    PubMed Central

    Singer, I I; Kawka, D W; Bayne, E K; Donatelli, S A; Weidner, J R; Williams, H R; Ayala, J M; Mumford, R A; Lark, M W; Glant, T T

    1995-01-01

    The destruction of articular cartilage in immune inflammatory arthritic disease involves the proteolytic degradation of its extracellular matrix. The role of activated matrix metalloproteinases (MMPs) in the chondrodestructive process was studied by identifying a selective cleavage product of aggrecan in murine arthritis models initiated by immunization with either type II collagen or proteoglycan. We conducted semiquantitative immunocytochemical studies of VDIPEN341 using a monospecific polyclonal antibody requiring the free COOH group of the COOH-terminal Asn for epitope detection. This antibody recognizes the aggrecan G1 domain fragment generated by MMP [i.e., stromelysin (SLN) or gelatinase A] cleavage of aggrecan between Asn341-Phe342 but does not recognize intact aggrecan. VDIPEN was undetectable in normal mouse cartilage but was observed in the articular cartilage (AC) of mice with collagen-induced arthritis 10 d after immunization, without histological damage and clinical symptoms. This aggrecan neoepitope was colocalized with high levels of glycosaminoglycans (GAGs) in pericellular matrices of AC chondrocytes but was not seen at the articular surface at this early time. Digestion of normal (VDIPEN negative) mouse paw cryosections with SLN also produced heavy pericellular VDIPEN labeling. Computer-based image analysis showed that the amount of VDIPEN expression increased dramatically by 20 d (70% of the SLN maximum) and was correlated with GAG depletion. Both infiltration of inflammatory cells into the synovial cavity and early AC erosion were also very prominent at this time. Analysis of adjacent sections showed that both induction of VDIPEN and GAG depletion were strikingly codistributed within sites of articular cartilage damage. Similar results occurred in proteoglycan-induced arthritis, a more progressive and chronic model of inflammatory arthritis. These studies demonstrate for the first time the MMP-dependent catabolism of aggrecan at sites of

  10. Mechanical Stimulation Protocols of Human Derived Cells in Articular Cartilage Tissue Engineering - A Systematic Review.

    PubMed

    Khozoee, Baktash; Mafi, Pouya; Mafi, Reza; Khan, Wasim S

    2017-01-01

    Mechanical stimulation is a key factor in articular cartilage generation and maintenance. Bioreactor systems have been designed and built in order to deliver specific types of mechanical stimulation. The focus has been twofold, applying a type of preconditioning in order to stimulate cell differentiation, and to simulate in vivo conditions in order to gain further insight into how cells respond to different stimulatory patterns. Due to the complex forces at work within joints, it is difficult to simulate mechanical conditions using a bioreactor. The aim of this review is to gain a deeper understanding of the complexities of mechanical stimulation protocols by comparing those employed in bioreactors in the context of tissue engineering for articular cartilage, and to consider their effects on cultured cells. Allied and Complementary Medicine 1985 to 2016, Ovid MEDLINE[R] 1946 to 2016, and Embase 1974 to 2016 were searched using key terms. Results were subject to inclusion and exclusion criteria, key findings summarised into a table and subsequently discussed. Based on this review it is overwhelmingly clear that mechanical stimulation leads to increased chondrogenic properties in the context of bioreactor articular cartilage tissue engineering using human cells. However, given the variability and lack of controlled factors between research articles, results are difficult to compare, and a standardised method of evaluating stimulation protocols proved challenging. With improved standardisation in mechanical stimulation protocol reporting, bioreactor design and building processes, along with a better understanding of joint behaviours, we hope to perform a meta-analysis on stimulation protocols and methods.

  11. Regeneration of articular cartilage in healer and non-healer mice

    PubMed Central

    Rai, Muhammad Farooq; Sandell, Linda J.

    2015-01-01

    Mammals rarely regenerate their lost or injured tissues into adulthood. MRL/MpJ mouse strain initially identified to heal full-thickness ear wounds now represents a classical example of mammalian wound regeneration since it can heal a spectrum of injuries such as skin and cardiac wounds, nerve injuries and knee articular cartilage lesions. In addition to MRL/MpJ, a few other mouse strains such as LG/J (a parent of MRL/MpJ) and LGXSM-6 (arising from an intercross between LG/J and SM/J mouse strains) have now been recognized to possess regenerative/healing abilities for articular cartilage and ear wound injuries that are similar, if not superior, to MRL/MpJ mice. While some mechanisms underlying regenerative potential have been begun to emerge, a complete set of biological processes and pathways still needs to be elucidated. Using a panel of healer and non-healer mouse strains, our recent work has provided some insights into the genes that could potentially be associated with healing potential. Future mechanistic studies can help seek the Holy Grail of regenerative medicine. This review highlights the regenerative capacity of selected mouse strains for articular cartilage, in particular, and lessons from other body tissues, in general. PMID:25173437

  12. Articular cartilage friction increases in hip joints after the removal of acetabular labrum.

    PubMed

    Song, Yongnam; Ito, Hiroshi; Kourtis, Lampros; Safran, Marc R; Carter, Dennis R; Giori, Nicholas J

    2012-02-02

    The acetabular labrum is believed to have a sealing function. However, a torn labrum may not effectively prevent joint fluid from escaping a compressed joint, resulting in impaired lubrication. We aimed to understand the role of the acetabular labrum in maintaining a low friction environment in the hip joint. We did this by measuring the resistance to rotation (RTR) of the hip, which reflects the friction of the articular cartilage surface, following focal and complete labrectomy. Five cadaveric hips without evidence of osteoarthritis and impingement were tested. We measured resistance to rotation of the hip joint during 0.5, 1, 2, and 3 times body weight (BW) cyclic loading in the intact hip, and after focal and complete labrectomy. Resistance to rotation, which reflects articular cartilage friction in an intact hip was significantly increased following focal labrectomy at 1-3 BW loading, and following complete labrectomy at all load levels. The acetabular labrum appears to maintain a low friction environment, possibly by sealing the joint from fluid exudation. Even focal labrectomy may result in increased joint friction, a condition that may be detrimental to articular cartilage and lead to osteoarthritis.

  13. Temperature affects transport of polysaccharides and proteins in articular cartilage explants.

    PubMed

    Moeini, Mohammad; Lee, Kwan-Bong; Quinn, Thomas M

    2012-07-26

    Solute transport phenomena mediate many aspects of the physiology and contrast agent-based clinical imaging of articular cartilage. Temperatures up to 10°C below standard body temperature (37°C) are common in articulating joints during normal activities and clinically (e.g. cold treatment of injuries). Therefore it is of interest to characterize the effects of temperature changes on solute transport parameters in cartilage. A range of fluorescent solutes including fluorescein isothiocyanate, 4 and 40kDa dextrans, myoglobin, insulin and chondroitin sulfate were prepared and used in assays of solute effective partition coefficient and effective diffusivity in bovine intermediate zone articular cartilage explants maintained at 10, 22 or 37°C. Trends for increasing partition coefficient with increasing temperature were evident for all solutes except chondroitin sulfate, with significant changes between 22 and 37°C for 4kDa dextran, insulin and myoglobin. Diffusivities of most solutes tested also tended to increase with increasing temperature, with significant changes between 10 and 22°C for FITC, 40kDa dextran and myoglobin. Oddly, insulin diffusivity decreased significantly as temperature increased from 22 to 37°C while chondroitin sulfate diffusivity exhibited no clear temperature dependence. These results highlight solute-specific temperature dependences of transport phenomena which may depend upon molecular weight, chemical structure, molecular conformation, and solute-matrix and solute-solute interactions. The articular cartilage explants themselves exhibited small but significant changes in water and glycosaminoglycan contents during experiments, underscoring the importance of solute-matrix interactions. Solute transport parameters in cartilage and their temperature dependences are therefore not easily predicted, and case-by-case experimental determination may be essential.

  14. Effects of growth and exercise on composition, structural maturation and appearance of osteoarthritis in articular cartilage of hamsters

    PubMed Central

    Julkunen, Petro; Halmesmäki, Esa P; Iivarinen, Jarkko; Rieppo, Lassi; Närhi, Tommi; Marjanen, Juho; Rieppo, Jarno; Arokoski, Jari; Brama, Pieter A; Jurvelin, Jukka S; Helminen, Heikki J

    2010-01-01

    Articular cartilage composition and structure are maintained and remodeled by chondrocytes under the influence of loading. Exercise-induced changes in the composition, structure, mechanical properties and tissue integrity of growing and aging hamster articular cartilage were investigated. Articular cartilage samples (n = 191) were harvested from the proximal tibiae of hamsters aged 1, 3, 6, 12 and 15 months. The hamsters were divided into runners and controls. The runners had free access to a running wheel between 1 and 3 months (runner groups 3-, 12- and 15-month-old hamsters) or 1 and 6 months (runner group 6-month-old hamsters) of age. Control animals were subjected to a sedentary lifestyle. Mechanical indentation tests and depth-wise compositional and structural analyses were performed for the cartilage samples. Furthermore, the integrity of articular cartilage was assessed using histological osteoarthritis grading. Exercise affected the collagen network organization after a 5-month exercise period, especially in the middle and deep zones. However, no effect on the mechanical properties was detected after exercise. Before the age of 12 months, the runners showed less osteoarthritis than the controls, whereas at 15 months of age the situation was reversed. It is concluded that, in hamsters, physical exercise at a young age enhances cartilage maturation and alters the depth-wise cartilage structure and composition. This may be considered beneficial. However, exercise at a young age demonstrated adverse effects on cartilage at a later age with a significant increase in the incidence of osteoarthritis. PMID:20646109

  15. Characterizing depth-dependent refractive index of articular cartilage subjected to mechanical wear or enzymic degeneration

    NASA Astrophysics Data System (ADS)

    Wang, Kuyu; Wu, Jianping; Day, Robert; Kirk, Thomas Brett; Hu, Xiaozhi

    2016-09-01

    Utilizing a laser scanning confocal microscope system, the refractive indices of articular cartilage (AC) with mechanical or biochemical degenerations were characterized to investigate whether potential correlations exist between refractive index (RI) and cartilage degeneration. The cartilage samples collected from the medial femoral condyles of kangaroo knees were mechanically degenerated under different loading patterns or digested in trypsin solution with different concentrations. The sequences of RI were then measured from cartilage surface to deep region and the fluctuations of RI were quantified considering combined effects of fluctuating frequency and amplitude. The compositional and microstructural alterations of cartilage samples were assessed with histological methods. Along with the loss of proteoglycans, the average RI of cartilage increased and the local fluctuation of RI became stronger. Short-term high-speed test induced little influence to both the depth fluctuation and overall level of RI. Long-term low-speed test increased the fluctuation of RI but the average RI was barely changed. The results substantially demonstrate that RI of AC varies with both compositional and structural alterations and is potentially an indicator for the degeneration of AC.

  16. MicroRNA-181b regulates articular chondrocytes differentiation and cartilage integrity.

    PubMed

    Song, Jinsoo; Lee, Myeungsu; Kim, Dongkyun; Han, Jiyeon; Chun, Churl-Hong; Jin, Eun-Jung

    2013-02-08

    MicroRNAs are endogenous gene regulators that have been implicated in various developmental and pathological processes. However, the precise identities and functions of the miRNAs involved in cartilage development are not yet well understood. Here, we report that miR-181b regulates chondrocyte differentiation and maintains cartilage integrity, and is thus a potent therapeutic target. MiR-181b was significantly down-regulated during chondrogenic differentiation of TGF-β3-stimulated limb mesenchymal cells, but it was significantly up-regulated in osteoarthritic chondrocytes isolated from the cartilage of osteoarthritis patients. The use of a mimic or an inhibitor to alter miR-181b levels in chondroblasts and articular chondrocytes showed that attenuation of miR-181b reduced MMP-13 expression while inducing type II collagen expression. Furthermore, over-expression of anti-miR-181b significantly reduced the cartilage destruction caused by DMM surgery in mice. In sum, our data suggest that miR-181b is a negative regulator of cartilage development, and that inhibition of miR-181b could be an effective therapeutic strategy for cartilage-related disease.

  17. Three-Dimensional Printing Articular Cartilage: Recapitulating the Complexity of Native Tissue.

    PubMed

    Guo, Ting; Lembong, Josephine; Zhang, Lijie Grace; Fisher, John P

    2016-12-27

    In the past few decades, the field of tissue engineering combined with rapid prototyping (RP) techniques has been successful in creating biological substitutes that mimic tissues. Its applications in regenerative medicine have drawn efforts in research from various scientific fields, diagnostics, and clinical translation to therapies. While some areas of therapeutics are well developed, such as skin replacement, many others such as cartilage repair can still greatly benefit from tissue engineering and RP due to the low success and/or inefficiency of current existing, often surgical treatments. Through fabrication of complex scaffolds and development of advanced materials, RP provides a new avenue for cartilage repair. Computer-aided design and three-dimensional (3D) printing allow the fabrication of modeled cartilage scaffolds for repair and regeneration of damaged cartilage tissues. Specifically, the various processes of 3D printing will be discussed in details, both cellular and acellular techniques, covering the different materials, geometries, and operational printing conditions for the development of tissue-engineered articular cartilage. Finally, we conclude with some insights on future applications and challenges related to this technology, especially using 3D printing techniques to recapitulate the complexity of native structure for advanced cartilage regeneration.

  18. Galectin-3 Binds to Lubricin and Reinforces the Lubricating Boundary Layer of Articular Cartilage

    NASA Astrophysics Data System (ADS)

    Reesink, Heidi L.; Bonnevie, Edward D.; Liu, Sherry; Shurer, Carolyn R.; Hollander, Michael J.; Bonassar, Lawrence J.; Nixon, Alan J.

    2016-05-01

    Lubricin is a mucinous, synovial fluid glycoprotein that enables near frictionless joint motion via adsorption to the surface of articular cartilage and its lubricating properties in solution. Extensive O-linked glycosylation within lubricin’s mucin-rich domain is critical for its boundary lubricating function; however, it is unknown exactly how glycosylation facilitates cartilage lubrication. Here, we find that the lubricin glycome is enriched with terminal β-galactosides, known binding partners for a family of multivalent lectins called galectins. Of the galectin family members present in synovial fluid, we find that galectin-3 is a specific, high-affinity binding partner for lubricin. Considering the known ability of galectin-3 to crosslink glycoproteins, we hypothesized that galectins could augment lubrication via biomechanical stabilization of the lubricin boundary layer. We find that competitive inhibition of galectin binding results in lubricin loss from the cartilage surface, and addition of multimeric galectin-3 enhances cartilage lubrication. We also find that galectin-3 has low affinity for the surface layer of osteoarthritic cartilage and has reduced affinity for sialylated O-glycans, a glycophenotype associated with inflammatory conditions. Together, our results suggest that galectin-3 reinforces the lubricin boundary layer; which, in turn, enhances cartilage lubrication and may delay the onset and progression of arthritis.

  19. Galectin-3 Binds to Lubricin and Reinforces the Lubricating Boundary Layer of Articular Cartilage

    PubMed Central

    Reesink, Heidi L.; Bonnevie, Edward D.; Liu, Sherry; Shurer, Carolyn R.; Hollander, Michael J.; Bonassar, Lawrence J.; Nixon, Alan J.

    2016-01-01

    Lubricin is a mucinous, synovial fluid glycoprotein that enables near frictionless joint motion via adsorption to the surface of articular cartilage and its lubricating properties in solution. Extensive O-linked glycosylation within lubricin’s mucin-rich domain is critical for its boundary lubricating function; however, it is unknown exactly how glycosylation facilitates cartilage lubrication. Here, we find that the lubricin glycome is enriched with terminal β-galactosides, known binding partners for a family of multivalent lectins called galectins. Of the galectin family members present in synovial fluid, we find that galectin-3 is a specific, high-affinity binding partner for lubricin. Considering the known ability of galectin-3 to crosslink glycoproteins, we hypothesized that galectins could augment lubrication via biomechanical stabilization of the lubricin boundary layer. We find that competitive inhibition of galectin binding results in lubricin loss from the cartilage surface, and addition of multimeric galectin-3 enhances cartilage lubrication. We also find that galectin-3 has low affinity for the surface layer of osteoarthritic cartilage and has reduced affinity for sialylated O-glycans, a glycophenotype associated with inflammatory conditions. Together, our results suggest that galectin-3 reinforces the lubricin boundary layer; which, in turn, enhances cartilage lubrication and may delay the onset and progression of arthritis. PMID:27157803

  20. Biochemical and metabolic abnormalities in normal and osteoarthritic human articular cartilage

    SciTech Connect

    Ryu, J.; Treadwell, B.V.; Mankin, H.J.

    1984-01-01

    Incorporation of radioactive precursors into macromolecules was studied with human normal and osteoarthritic articular cartilage organ culture. Analysis of the salt extracted matrix components separated by cesium chloride buoyant density gradient centrifugation showed an increase in the specific activities of all gradient fractions prepared from the osteoarthritic cartilage. Further analysis of these fractions showed the osteoarthritic cartilage contained 5 times as much sulfate incorporated into proteoglycans, and an even greater amount of 3H-glucosamine incorporated into material sedimenting to the middle of the gradient. Greater than half of this radioactive middle fraction appears to be hyaluronate, as judged by the position it elutes from a DEAE column and its susceptibility to hyaluronidase digestion. This study supports earlier findings showing increased rates of macromolecular synthesis in osteoarthritis, and in addition, an even greater synthetic rate for hyaluronic acid is demonstrated.

  1. Changes of articular cartilage and subchondral bone after extracorporeal shockwave therapy in osteoarthritis of the knee

    PubMed Central

    Wang, Ching-Jen; Cheng, Jai-Hong; Chou, Wen-Yi; Hsu, Shan-Ling; Chen, Jen-Hung; Huang, Chien-Yiu

    2017-01-01

    We assessed the pathological changes of articular cartilage and subchondral bone on different locations of the knee after extracorporeal shockwave therapy (ESWT) in early osteoarthritis (OA). Rat knees under OA model by anterior cruciate ligament transaction (ACLT) and medial meniscectomy (MM) to induce OA changes. Among ESWT groups, ESWT were applied to medial (M) femur (F) and tibia (T) condyles was better than medial tibia condyle, medial femur condyle as well as medial and lateral (L) tibia condyles in gross osteoarthritic areas (p<0.05), osteophyte formation and subchondral sclerotic bone (p<0.05). Using sectional cartilage area, modified Mankin scoring system as well as thickness of calcified and un-calcified cartilage analysis, the results showed that articular cartilage damage was ameliorated and T+F(M) group had the most protection as compared with other locations (p<0.05). Detectable cartilage surface damage and proteoglycan loss were measured and T+F(M) group showed the smallest lesion score among other groups (p<0.05). Micro-CT revealed significantly improved in subchondral bone repair in all ESWT groups compared to OA group (p<0.05). There were no significantly differences in bone remodeling after ESWT groups except F(M) group. In the immunohistochemical analysis, T+F(M) group significant reduced TUNEL activity, promoted cartilage proliferation by observation of PCNA marker and reduced vascular invasion through observation of CD31 marker for angiogenesis compared to OA group (P<0.001). Overall the data suggested that the order of the effective site of ESWT was T+F(M) ≧ T(M) > T(M+L) > F(M) in OA rat knees. PMID:28367081

  2. Near Infrared Spectroscopic Mapping of Functional Properties of Equine Articular Cartilage.

    PubMed

    Sarin, Jaakko K; Amissah, Michael; Brommer, Harold; Argüelles, David; Töyräs, Juha; Afara, Isaac O

    2016-11-01

    Mechanical properties of articular cartilage are vital for normal joint function, which can be severely compromised by injuries. Quantitative characterization of cartilage injuries, and evaluation of cartilage stiffness and thickness by means of conventional arthroscopy is poorly reproducible or impossible. In this study, we demonstrate the potential of near infrared (NIR) spectroscopy for predicting and mapping the functional properties of equine articular cartilage at and around lesion sites. Lesion and non-lesion areas of interests (AI, N = 44) of equine joints (N = 5) were divided into grids and NIR spectra were acquired from all grid points (N = 869). Partial least squares (PLS) regression was used to investigate the correlation between the absorbance spectra and thickness, equilibrium modulus, dynamic modulus, and instantaneous modulus at the grid points of 41 AIs. Subsequently, the developed PLS models were validated with spectral data from the grid points of 3 independent AIs. Significant correlations were obtained between spectral data and cartilage thickness (R (2) = 70.3%, p < 0.0001), equilibrium modulus (R (2) = 67.8%, p < 0.0001), dynamic modulus (R (2) = 68.9%, p < 0.0001) and instantaneous modulus (R (2) = 41.8%, p < 0.0001). Relatively low errors were observed in the predicted thickness (5.9%) and instantaneous modulus (9.0%) maps. Thus, if well implemented, NIR spectroscopy could enable arthroscopic evaluation and mapping of cartilage functional properties at and around lesion sites.

  3. The role of the Notch pathway in healthy and osteoarthritic articular cartilage: from experimental models to ex vivo studies

    PubMed Central

    2011-01-01

    Osteoarthritis is the most prevalent form of arthritis in the world. With the progressive ageing of the population, it is becoming a major public health problem. The involvement of certain signaling pathways, such as the Notch pathway, during cartilage pathology has been reported. In this review, we report on studies that investigated the expression pattern of the Notch family members in articular cartilage and the eventual involvement of this pathway in the modulation of the physiology and pathology of chondrocytes. Temporal and/or spatial modulation of this signaling pathway may help these cells to synthesize a new functional extracellular matrix and restore the functional properties of the articular cartilage. PMID:21457519

  4. Development of a Spring-Loaded Impact Device to Deliver Injurious Mechanical Impacts to the Articular Cartilage Surface

    PubMed Central

    Alexander, Peter G.; Song, Yingjie; Taboas, Juan M.; Chen, Faye H.; Melvin, Gary M.; Manner, Paul A.

    2013-01-01

    Objective: Traumatic impacts on the articular joint surface in vitro are known to lead to degeneration of the cartilage. The main objective of this study was to develop a spring-loaded impact device that can be used to deliver traumatic impacts of consistent magnitude and rate and to find whether impacts cause catabolic activities in articular cartilage consistent with other previously reported impact models and correlated with the development of osteoarthritic lesions. In developing the spring-loaded impactor, the operating hypothesis is that a single supraphysiologic impact to articular cartilage in vitro can affect cartilage integrity, cell viability, sulfated glycosaminoglycan and inflammatory mediator release in a dose-dependent manner. Design: Impacts of increasing force are delivered to adult bovine articular cartilage explants in confined compression. Impact parameters are correlated with tissue damage, cell viability, matrix and inflammatory mediator release, and gene expression 24 hours postimpact. Results: Nitric oxide release is first detected after 7.7 MPa impacts, whereas cell death, glycosaminoglycan release, and prostaglandin E2 release are first detected at 17 MPa. Catabolic markers increase linearly to maximal levels after ≥36 MPa impacts. Conclusions: A single supraphysiologic impact negatively affects cartilage integrity, cell viability, and GAG release in a dose-dependent manner. Our findings showed that 7 to 17 MPa impacts can induce cell death and catabolism without compromising the articular surface, whereas a 17 MPa impact is sufficient to induce increases in most common catabolic markers of osteoarthritic degeneration. PMID:26069650

  5. In Situ Recruitment of Human Bone Marrow-Derived Mesenchymal Stem Cells Using Chemokines for Articular Cartilage Regeneration.

    PubMed

    Park, Min Sung; Kim, Yun Hee; Jung, Youngmee; Kim, Soo Hyun; Park, Jong Chul; Yoon, Dong Suk; Kim, Sung-Hwan; Lee, Jin Woo

    2015-01-01

    Bone marrow-derived mesenchymal stem cells (BMSCs) are a good cell source for regeneration of cartilage as they can migrate directly to the site of cartilage injury and differentiate into articular chondrocytes. Articular cartilage defects do not heal completely due to the lack of chondrocytes or BMSCs at the site of injury. In this study, the chemotaxis of BMSCs toward chemokines, which may give rise to a complete regeneration of the articular cartilage, was investigated. CCR2, CCR4, CCR6, CXCR1, and CXCR2 were expressed in normal BMSCs and were increased significantly upon treatment with proinflammatory cytokines. BMSC migration was increased by MIP-3α and IL-8 more than by MCP-1 or SDF-1α. IL-8 and MIP-3α significantly enhanced the chemotaxis of BMSCs compared with MCP-1, SDF-1α, or PBS. Human BMSC recruitment to transplanted scaffolds containing either IL-8 or MIP-3α significantly increased in vivo compared to scaffolds containing PBS. Furthermore, IL-8- and MIP-3α-containing scaffolds enhanced tissue regeneration of an osteochondral defect site in beagle knee articular cartilage. Therefore, this study suggests that IL-8 and MIP-3α are the candidates that induce the regeneration of damaged articular cartilage.

  6. Sodium Visibility and Quantitation in Intact Bovine Articular Cartilage Using High Field 23Na MRI and MRS

    NASA Astrophysics Data System (ADS)

    Shapiro, Erik M.; Borthakur, Arijitt; Dandora, Rahul; Kriss, Antigone; Leigh, John S.; Reddy, Ravinder

    2000-01-01

    Noninvasive methods of detecting cartilage degeneration can have an impact on identifying the early stages of osteoarthritis. Accurate measurement of sodium concentrations within the cartilage matrix provides a means for analyzing tissue integrity. Here a method is described for quantitating sodium concentration and visibility in cartilage, with general applications to all tissue types. The sodium concentration in bovine patellar cartilage plugs was determined by three different methods: NMR spectroscopy of whole cartilage plugs, NMR spectroscopy of liquefied cartilage in concentrated HCl, and inductively coupled plasma emission spectroscopy. Whole bovine patellae were imaged with relaxation normalized calibration phantoms to ascertain sodium concentrations inside the articular cartilage. Sodium concentrations in intact articular cartilage were found to range from ∼200 mM on the edges to ∼390 mM in the center, with an average of ∼320 mM in five separate bovine patellae studied. In essence, we have created sodium distribution maps of the cartilage, showing for the first time, spatial variations of sodium concentration in intact cartilage. This average concentration measurement correlates very well with the values obtained from the spectroscopic methods. Furthermore, sodium was found to be 100% NMR visible in cartilage plugs. Applications of this method in diagnosing and monitoring treatment of osteoarthritis are discussed.

  7. Ultrasound palpation for fast in-situ quantification of articular cartilage stiffness, thickness and relaxation capacity.

    PubMed

    Schöne, M; Schulz, R M; Tzschätzsch, H; Varga, P; Raum, K

    2017-02-16

    Most current cartilage testing devices require the preparation of excised samples and therefore do not allow intra-operative application for diagnostic purposes. The gold standard during open or arthroscopic surgery is still the subjective perception of manual palpation. This work presents a new diagnostic method of ultrasound palpation (USP) to acquire applied stress and strain data during manual palpation of articular cartilage. With the proposed method, we obtain cartilage thickness and stiffness. Moreover, repeated palpations allow the quantification of relaxation effects. USP measurements on elastomer phantoms demonstrated very good repeatability for both, stage-guided (97.2%) and handheld (96.0%) applications. The USP measurements were compared with conventional indentation experiments and revealed very good agreement on elastomer phantoms ([Formula: see text]) and good agreement on porcine cartilage samples ([Formula: see text]). Artificially degenerated cartilage samples showed reduced stiffness, weak capacity to relax after palpation and an increase of stiffness of approximately 50% with each single palpation. Intact cartilage was measured by USP directly at the patella (in situ) and after excision and removal of the subchondral bone (ex situ), leading to stiffness values of [Formula: see text] and [Formula: see text] ([Formula: see text]), respectively. The results demonstrate the potential of the USP system for cartilage testing, its sensitivity to degenerative changes and as a method for quantifying relaxation processes by means of repeated palpations. Furthermore, the differences in the results of in-situ and ex-situ measurements are of general interest, since such comparison has not been reported previously. We point out the limited comparability of ex-situ cartilage with its in-situ biomechanical behavior.

  8. Transthyretin deposition in articular cartilage: a novel mechanism in the pathogenesis of osteoarthritis

    PubMed Central

    Akasaki, Yukio; Reixach, Natàlia; Matsuzaki, Tokio; Alvarez-Garcia, Oscar; Olmer, Merissa; Iwamoto, Yukihide; Buxbaum, Joel N.; Lotz, Martin K.

    2015-01-01

    Objectives Amyloid deposits are prevalent in osteoarthritis (OA)-affected joints. This study defined the dominant precursor and determined if the deposits affect chondrocyte functions. Methods Amyloid deposition in normal and OA human knee cartilage was determined by Congo red staining. Transthyretin (TTR) in cartilage and synovial fluid was analyzed by immunohistochemistry and western blotting. The effects of recombinant amyloidogenic and non-amyloidogenic TTR variants were tested in human chondrocyte cultures. Results Normal cartilage from young donors did not contain detectable amyloid deposits but 58% (7/12) of aged normal cartilage and 100% (12/12) of OA cartilage samples showed Congo red staining with green birefringence under polarized light. TTR, located predominantly at the cartilage surfaces, was detected in all OA and a majority of aged, but not young normal cartilage. Chondrocytes and synoviocytes did not contain significant amounts of TTR mRNA. Synovial fluid TTR levels were similar in normal and OA knees. In cultured chondrocytes, only an amyloidogenic TTR variant induced cell death, the expression of proinflammatory cytokines, and extracellular matrix degrading enzymes. The effects of amyloidogenic TTR on gene expression were mediated by in part by Toll-like receptor-4, Receptor for advanced glycation endproducts and p38 MAP kinase. TTR-induced cytotoxicity was inhibited by resveratrol, a plant polyphenol that stabilizes the native tetrameric structure of TTR. Conclusions The findings are the first to suggest that TTR amyloid deposition contributes to cell and extracellular matrix damage in articular cartilage in human OA and that therapies designed to reduce TTR amyloid formation might be useful. PMID:25940564

  9. 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.

  10. Relative contribution of articular cartilage's constitutive components to load support depending on strain rate.

    PubMed

    Quiroga, J M Párraga; Wilson, W; Ito, K; van Donkelaar, C C

    2017-02-01

    Cartilage is considered a biphasic material in which the solid is composed of proteoglycans and collagen. In biphasic tissue, the hydraulic pressure is believed to bear most of the load under higher strain rates and its dissipation due to fluid flow determines creep and relaxation behavior. In equilibrium, hydraulic pressure is zero and load bearing is transferred to the solid matrix. The viscoelasticity of the collagen network also contributes to its time-dependent behavior, and the osmotic pressure to load bearing in equilibrium. The aim of the present study was to determine the relative contributions of hydraulic pressure, viscoelastic collagen stress, solid matrix stiffness and osmotic pressure to load carriage in cartilage under transient and equilibrium conditions. Unconfined compression experiments were simulated using a fibril-reinforced poroviscoelastic model of articular cartilage, including water, fibrillar viscoelastic collagen and non-fibrillar charged glycosaminoglycans. The relative contributions of hydraulic and osmotic pressures and stresses in the fibrillar and non-fibrillar network were evaluated in the superficial, middle and deep zone of cartilage under five different strain rates and after relaxation. Initially upon loading, the hydraulic pressure carried most of the load in all three zones. The osmotic swelling pressure carried most of the equilibrium load. In the surface zone, where the fibers were loaded in tension, the collagen network carried 20 % of the load for all strain rates. The importance of these fibers was illustrated by artificially modifying the fiber architecture, which reduced the overall stiffness of cartilage in all conditions. In conclusion, although hydraulic pressure dominates the transient behavior during cartilage loading, due to its viscoelastic nature the superficial zone collagen fibers carry a substantial part of the load under transient conditions. This becomes increasingly important with higher strain rates. The

  11. A study on the role of articular cartilage soft tissue constitutive form in models of whole knee biomechanics.

    PubMed

    Marchi, Benjamin C; Arruda, Ellen M

    2017-02-01

    The mechanical behaviors of biological soft tissues are challenging to describe abstractly, with each individual tissue potentially characterized by its own unique nonlinear, anisotropic, and viscoelastic properties. These complexities are exacerbated by patient to patient variability, both mechanically and anatomically, and by inherent constitutive heterogeneity. Despite these challenges, computational models of whole knee biomechanics can be instrumental in describing the onset and progression of injury and disease. In this work, a three-dimensional whole knee computational model was developed using patient-specific anatomy, containing tissues with constitutive relationships built from relevant experimental investigations. In an effort to address the common assumption of linear elastic descriptions of articular cartilage in whole knee models, this work investigates the implications, with respect to macroscopic kinematics and local deformation, of incorporating physiologically motivated and mechanically accurate constitutive heterogeneity in articular cartilage, highlighting the sensitivities of each corresponding level of constitutive complexity. We show how the inclusion of representative cartilage material models affects deformation distributions within the joint, as well as relative joint motion. In particular, the assumption of linear elasticity in articular cartilage results in an overprediction of joint motion and significantly affects predicted local cartilage strains, while full-field, mechanically heterogeneous cartilage descriptions have a less drastic effect at both the tissue and joint levels. Nonetheless, joints containing complete descriptions of articular cartilage heterogeneity may be an integral component in building comprehensive computational tools to advance our understanding of injury and disease mechanisms.

  12. Modeling the matrix of articular cartilage using a continuous fiber angular distribution predicts many observed phenomena.

    PubMed

    Ateshian, Gerard A; Rajan, Vikram; Chahine, Nadeen O; Canal, Clare E; Hung, Clark T

    2009-06-01

    Cartilage is a hydrated soft tissue whose solid matrix consists of negatively charged proteoglycans enmeshed within a fibrillar collagen network. Though many aspects of cartilage mechanics are well understood today, most notably in the context of porous media mechanics, there remain a number of responses observed experimentally whose prediction from theory has been challenging. In this study the solid matrix of cartilage is modeled with a continuous fiber angular distribution, where fibers can only sustain tension, swelled by the osmotic pressure of a proteoglycan ground matrix. It is shown that this representation of cartilage can predict a number of observed phenomena in relation to the tissue's equilibrium response to mechanical and osmotic loading, when flow-dependent and flow-independent viscoelastic effects have subsided. In particular, this model can predict the transition of Poisson's ratio from very low values in compression (approximately 0.02) to very high values in tension (approximately 2.0). Most of these phenomena cannot be explained when using only three orthogonal fiber bundles to describe the tissue matrix, a common modeling assumption used to date. The main picture emerging from this analysis is that the anisotropy of the fibrillar matrix of articular cartilage is intimately dependent on the mechanism of tensed fiber recruitment, in the manner suggested by our recent theoretical study (Ateshian, 2007, ASME J. Biomech. Eng., 129(2), pp. 240-249).

  13. Modeling the Matrix of Articular Cartilage Using a Continuous Fiber Angular Distribution Predicts Many Observed Phenomena

    PubMed Central

    Ateshian, Gerard A.; Rajan, Vikram; Chahine, Nadeen O.; Canal, Clare E.; Hung, Clark T.

    2010-01-01

    Background Cartilage is a hydrated soft tissue whose solid matrix consists of negatively charged proteoglycans enmeshed within a fibrillar collagen network. Though many aspects of cartilage mechanics are well understood today, most notably in the context of porous media mechanics, there remain a number of responses observed experimentally whose prediction from theory has been challenging. Method of approach In this study the solid matrix of cartilage is modeled with a continuous fiber angular distribution, where fibers can only sustain tension, swelled by the osmotic pressure of a proteoglycan ground matrix. Results It is shown that this representation of cartilage can predict a number of observed phenomena in relation to the tissue’s equilibrium response to mechanical and osmotic loading, when flow-dependent and flow-independent viscoelastic effects have subsided. In particular, this model can predict the transition of Poisson’s ratio from very low values in compression (~0.02) to very high values in tension (~2.0). Most of these phenomena cannot be explained when using only three orthogonal fiber bundles to describe the tissue matrix, a common modeling assumption used to date. Conclusions The main picture emerging from this analysis is that the anisotropy of the fibrillar matrix of articular cartilage is intimately dependent on the mechanism of tensed fiber recruitment, in the manner suggested by our recent theoretical study (G. A. Ateshian. J Biomech Eng, 129(2):240-9, 2007). PMID:19449957

  14. 3-D high-frequency ultrasound backscatter analysis of human articular cartilage.

    PubMed

    Männicke, Nils; Schöne, Martin; Gottwald, Matthias; Göbel, Felix; Oelze, Michael L; Raum, Kay

    2014-01-01

    High-frequency ultrasound is a promising method for non-invasive characterization of cartilage degeneration. Surface reflection and integrated spectral parameters are often used. In the work described here, human cartilage samples with varying degrees of degeneration were measured using a 40-MHz transducer. Backscatter signals originating from the superficial and transitional zones of cartilage were analyzed using amplitude, spectral and envelope statistical parameters and related to degenerative changes of the matrix given by the Mankin score. The results indicate an increased sensitivity of spectral slope and envelope statistical parameters to early matrix degeneration compared with conventional amplitude parameters. Furthermore, moderate correlations of chondrocyte number with backscatter amplitude and envelope statistics were observed, suggesting that at high frequencies, cells are one important scattering source in cartilage. An application of spectral and envelope statistical parameters to intra-articular ultrasound arthroscopy is conceivable and could improve the diagnostic potential of these examinations. Future studies are necessary to clarify the contributions of chondrocytes, extracellular matrix and collagen content to ultrasound backscatter to further improve the diagnostic potential of ultrasound for cartilage assessment.

  15. Of Mice, Men and Elephants: The Relation between Articular Cartilage Thickness and Body Mass

    PubMed Central

    Malda, Jos; de Grauw, Janny C.; Benders, Kim E. M.; Kik, Marja J. L.; van de Lest, Chris H. A.; Creemers, Laura B.; Dhert, Wouter J. A.; van Weeren, P. René

    2013-01-01

    Mammalian articular cartilage serves diverse functions, including shock absorption, force transmission and enabling low-friction joint motion. These challenging requirements are met by the tissue’s thickness combined with its highly specific extracellular matrix, consisting of a glycosaminoglycan-interspersed collagen fiber network that provides a unique combination of resilience and high compressive and shear resistance. It is unknown how this critical tissue deals with the challenges posed by increases in body mass. For this study, osteochondral cores were harvested post-mortem from the central sites of both medial and lateral femoral condyles of 58 different mammalian species ranging from 25 g (mouse) to 4000 kg (African elephant). Joint size and cartilage thickness were measured and biochemical composition (glycosaminoclycan, collagen and DNA content) and collagen cross-links densities were analyzed. Here, we show that cartilage thickness at the femoral condyle in the mammalian species investigated varies between 90 µm and 3000 µm and bears a negative allometric relationship to body mass, unlike the isometric scaling of the skeleton. Cellular density (as determined by DNA content) decreases with increasing body mass, but gross biochemical composition is remarkably constant. This however need not affect life-long performance of the tissue in heavier mammals, due to relatively constant static compressive stresses, the zonal organization of the tissue and additional compensation by joint congruence, posture and activity pattern of larger mammals. These findings provide insight in the scaling of articular cartilage thickness with body weight, as well as in cartilage biochemical composition and cellularity across mammalian species. They underscore the need for the use of appropriate in vivo models in translational research aiming at human applications. PMID:23437402

  16. Effect of glutaraldehyde fixation on the frictional response of immature bovine articular cartilage explants.

    PubMed

    Oungoulian, Sevan R; Hehir, Kristin E; Zhu, Kaicen; Willis, Callen E; Marinescu, Anca G; Merali, Natasha; Ahmad, Christopher S; Hung, Clark T; Ateshian, Gerard A

    2014-02-07

    This study examined functional properties and biocompatibility of glutaraldehyde-fixed bovine articular cartilage over several weeks of incubation at body temperature to investigate its potential use as a resurfacing material in joint arthroplasty. In the first experiment, treated cartilage disks were fixed using 0.02, 0.20 and 0.60% glutaraldehyde for 24h then incubated, along with an untreated control group, in saline for up to 28d at 37°C. Both the equilibrium compressive and tensile moduli increased nearly twofold in treated samples compared to day 0 control, and remained at that level from day 1 to 28; the equilibrium friction coefficient against glass rose nearly twofold immediately after fixation (day 1) but returned to control values after day 7. Live explants co-cultured with fixed explants showed no quantitative difference in cell viability over 28d. In general, no significant differences were observed between 0.20 and 0.60% groups, so 0.20% was deemed sufficient for complete fixation. In the second experiment, cartilage-on-cartilage frictional measurements were performed under a migrating contact configuration. In the treated group, one explant was fixed using 0.20% glutaraldehyde while the apposing explant was left untreated; in the control group both explants were left untreated. From day 1 to 28, the treated group exhibited either no significant difference or slightly lower friction coefficient than the untreated group. These results suggest that a properly titrated glutaraldehyde treatment can reproduce the desired functional properties of native articular cartilage and maintain these properties for at least 28d at body temperature.

  17. Heritability of Articular Cartilage Regeneration and its Association with Ear-Wound Healing

    PubMed Central

    Rai, Muhammad Farooq; Hashimoto, Shingo; Johnson, Eric E.; Janiszak, Kara L.; Fitzgerald, Jamie; Heber-Katz, Ellen; Cheverud, James M.; Sandell, Linda J.

    2012-01-01

    Objective Emerging evidence suggests that genetic components contribute significantly to cartilage degeneration in osteoarthritis pathophysiology but little evidence is available on genetics of cartilage regeneration. Therefore, we investigated cartilage regeneration in genetic murine models using common inbred strains and a set of recombinant inbred lines generated from LG/J (healer of ear-wounds) and SM/J (non-healer) inbred strains. Methods An acute full-thickness cartilage injury was introduced through microsurgery in the trochlear groove of 8-weeks old mice (N=265). Knee joints were sagittally sectioned and stained with toluidine blue to evaluate regeneration. For ear-wound phenotype, a bilateral 2-mm through-and-through puncture was made (N=229) at 6-weeks and healing outcomes measured after 30-days. Broad-sense heritability and genetic correlations were calculated for both phenotypes. Results Time-course studies from recombinant inbred lines show no significant regeneration until 16-weeks post-surgery; at that time, the strains can be segregated into three categories: good, intermediate and poor healers. Heritability (H2) showed that both cartilage regeneration (H2=26%; p=0.006) and ear-wound closure (H2=53%; p<0.00001) are significantly heritable. The genetic correlations between the two healing phenotypes for common inbred strains (r=0.92) and recombinant inbred lines (r=0.86) were found to be extremely high. Conclusion We report that i) articular cartilage regeneration is heritable, ii) the differences between the lines being due to genetic differences and iii) a strong genetic correlation between the two phenotypes exists indicating that they plausibly share a common genetic basis. We, therefore, surmise that LG/J by SM/J intercross can be used to dissect the genetic basis of variation in cartilage regeneration. PMID:22275233

  18. A biphasic viscohyperelastic fibril-reinforced model for articular cartilage: formulation and comparison with experimental data.

    PubMed

    García, José Jaime; Cortés, Daniel Humberto

    2007-01-01

    Experiments in articular cartilage have shown highly nonlinear stress-strain curves under finite deformations, nonlinear tension-compression response as well as intrinsic viscous effects of the proteoglycan matrix and the collagen fibers. A biphasic viscohyperelastic fibril-reinforced model is proposed here, which is able to describe the intrinsic viscoelasticity of the fibrillar and nonfibrillar components of the solid phase, the nonlinear tension-compression response and the nonlinear stress-strain curves under tension and compression. A viscohyperelastic constitutive equation was used for the matrix and the fibers encompassing, respectively, a hyperelastic function used previously for the matrix and a hyperelastic law used before to represent biological connective tissues. This model, implemented in an updated Lagrangian finite element code, displayed good ability to follow experimental stress-strain equilibrium curves under tension and compression for human humeral cartilage. In addition, curve fitting of experimental reaction force and lateral displacement unconfined compression curves showed that the inclusion of viscous effects in the matrix allows the description of experimental data with material properties for the fibers consistent with experimental tensile tests, suggesting that intrinsic viscous effects in the matrix of articular cartilage plays an important role in the mechanical response of the tissue.

  19. Effects of ultrasound beam angle and surface roughness on the quantitative ultrasound parameters of articular cartilage.

    PubMed

    Kaleva, E; Saarakkala, S; Jurvelin, J S; Virén, T; Töyräs, J

    2009-08-01

    High-resolution arthroscopic ultrasound imaging provides a potential quantitative technique for the diagnostics of early osteoarthritis. However, an uncontrolled, nonperpendicular angle of an ultrasound beam or the natural curvature of the cartilage surface may jeopardize the reliability of the ultrasound measurements. We evaluated systematically the effect of inclining an articular surface on the quantitative ultrasound parameters. Visually intact (n = 8) and mechanically degraded (n = 6) osteochondral bovine patella samples and spontaneously fibrillated (n = 1) and spontaneously proteoglycan depleted (n = 1) osteochondral human tibial samples were imaged using a 50-MHz scanning acoustic system. The surface of each sample was adjusted to predetermined inclination angles (0, 2, 5 and 7 degrees ) and five ultrasound scan lines along the direction of the inclination were analyzed. For each scan line, reflection coefficient (R), integrated reflection coefficient (IRC) and ultrasound roughness index (URI) were calculated. Nonperpendicularity of the cartilage surface was found to affect R, IRC and URI significantly (p < 0.05). Importantly, all ultrasound parameters were able to distinguish (p < 0.05) the mechanically degraded samples from the intact ones even though the angle of incidence of the ultrasound beam varied between 0 and 5 degrees among the samples. Diagnostically, the present findings are important because the natural curvature of the articular surface varies, and a perfect perpendicularity between the ultrasound beam and the surface of the cartilage may be challenging to achieve in a clinical measurement.

  20. Communication between paired chondrocytes in the superficial zone of articular cartilage

    PubMed Central

    Chi, Simon S; Rattner, Jerome B; Matyas, John R

    2004-01-01

    The regeneration and repair of cartilage damaged by injury or disease, a major goal of orthopaedic science, depends on understanding the structure and function of both the extracellular matrix and the chondrocytes. In this study, we explored the in situ organization and potential interactions between chondrocytes in the superficial zone of adult rabbit articular cartilage. Some chondrocytes in this zone were observed close together and appeared to be paired whereas others were solitary. The shared surfaces of a chondrocyte pair were separated by a narrow plate of extracellular matrix, into which extended small cytoplasmic projections from both cells. Furthermore, the spatial distribution of major cellular landmarks, such as the nucleus and centrosome as well as some intracellular proteins such as connexin-43, tended to be mirrored about this matrix plate. Fluorescence recovery after photobleaching revealed the fluorescent dye calcein–AM dye can pass between paired cells, and that the passage of this dye can be inhibited by the gap junction blocker octanol. These results illustrate that rapid cellular communication is possible between cells in the superficial layer of adult articular cartilage, which challenges the current thinking that these chondrocytes function in isolation. PMID:15575885

  1. Mesenchymal stem cells as a potent cell source for articular cartilage regeneration

    PubMed Central

    Baghaban Eslaminejad, Mohamadreza; Malakooty Poor, Elham

    2014-01-01

    Since articular cartilage possesses only a weak capacity for repair, its regeneration potential is considered one of the most important challenges for orthopedic surgeons. The treatment options, such as marrow stimulation techniques, fail to induce a repair tissue with the same functional and mechanical properties of native hyaline cartilage. Osteochondral transplantation is considered an effective treatment option but is associated with some disadvantages, including donor-site morbidity, tissue supply limitation, unsuitable mechanical properties and thickness of the obtained tissue. Although autologous chondrocyte implantation results in reasonable repair, it requires a two-step surgical procedure. Moreover, chondrocytes expanded in culture gradually undergo dedifferentiation, so lose morphological features and specialized functions. In the search for alternative cells, scientists have found mesenchymal stem cells (MSCs) to be an appropriate cellular material for articular cartilage repair. These cells were originally isolated from bone marrow samples and further investigations have revealed the presence of the cells in many other tissues. Furthermore, chondrogenic differentiation is an inherent property of MSCs noticed at the time of the cell discovery. MSCs are known to exhibit homing potential to the damaged site at which they differentiate into the tissue cells or secrete a wide spectrum of bioactive factors with regenerative properties. Moreover, these cells possess a considerable immunomodulatory potential that make them the general donor for therapeutic applications. All of these topics will be discussed in this review. PMID:25126383

  2. In-laboratory diffraction-enhanced X-ray imaging for articular cartilage.

    PubMed

    Muehleman, Carol; Fogarty, Daniel; Reinhart, Benjamin; Tzvetkov, Tochko; Li, Jun; Nesch, Ivan

    2010-07-01

    The loss of articular cartilage characteristic of osteoarthritis can only be diagnosed by joint space narrowing when conventional radiography is used. This is due to the lack of X-ray contrast of soft tissues. Whereas conventional radiography harnesses the X-ray attenuation properties of tissues, Diffraction Enhanced Imaging (DEI), a novel radiographic technique, allows the visualization of soft tissues simultaneous with calcified tissues by virtue of its ability to not only harness X-ray attenuation but also the X-ray refraction from tissue boundaries. Previously, DEI was dependent upon synchrotron X-rays, but more recently, the development of nonsynchrotron DEI units has been explored. These developments serve to elaborate the full potential of radiography. Here, we tested the potential of an in-laboratory DEI system, called Diffraction-Enhanced X-ray Imaging (DEXI), to render images of articular cartilage displaying varying degrees of degradation, ex vivo. DEXI allowed visualization of even early stages of cartilage degeneration such as surface fibrillation. This may be of eventual clinical significance for the diagnosis of early stages of degeneration, or at the very least, to visualize soft tissue degeneration simultaneous with bone changes.

  3. Flavonoid Compound Icariin Activates Hypoxia Inducible Factor-1α in Chondrocytes and Promotes Articular Cartilage Repair.

    PubMed

    Wang, Pengzhen; Zhang, Fengjie; He, Qiling; Wang, Jianqi; Shiu, Hoi Ting; Shu, Yinglan; Tsang, Wing Pui; Liang, Shuang; Zhao, Kai; Wan, Chao

    2016-01-01

    Articular cartilage has poor capability for repair following trauma or degenerative pathology due to avascular property, low cell density and migratory ability. Discovery of novel therapeutic approaches for articular cartilage repair remains a significant clinical need. Hypoxia is a hallmark for cartilage development and pathology. Hypoxia inducible factor-1alpha (HIF-1α) has been identified as a key mediator for chondrocytes to response to fluctuations of oxygen availability during cartilage development or repair. This suggests that HIF-1α may serve as a target for modulating chondrocyte functions. In this study, using phenotypic cellular screen assays, we identify that Icariin, an active flavonoid component from Herba Epimedii, activates HIF-1α expression in chondrocytes. We performed systemic in vitro and in vivo analysis to determine the roles of Icariin in regulation of chondrogenesis. Our results show that Icariin significantly increases hypoxia responsive element luciferase reporter activity, which is accompanied by increased accumulation and nuclear translocation of HIF-1α in murine chondrocytes. The phenotype is associated with inhibiting PHD activity through interaction between Icariin and iron ions. The upregulation of HIF-1α mRNA levels in chondrocytes persists during chondrogenic differentiation for 7 and 14 days. Icariin (10-6 M) increases the proliferation of chondrocytes or chondroprogenitors examined by MTT, BrdU incorporation or colony formation assays. Icariin enhances chondrogenic marker expression in a micromass culture including Sox9, collagen type 2 (Col2α1) and aggrecan as determined by real-time PCR and promotes extracellular matrix (ECM) synthesis indicated by Alcian blue staining. ELISA assays show dramatically increased production of aggrecan and hydroxyproline in Icariin-treated cultures at day 14 of chondrogenic differentiation as compared with the controls. Meanwhile, the expression of chondrocyte catabolic marker genes

  4. Flavonoid Compound Icariin Activates Hypoxia Inducible Factor-1α in Chondrocytes and Promotes Articular Cartilage Repair

    PubMed Central

    He, Qiling; Wang, Jianqi; Shiu, Hoi Ting; Shu, Yinglan; Tsang, Wing Pui; Liang, Shuang; Zhao, Kai; Wan, Chao

    2016-01-01

    Articular cartilage has poor capability for repair following trauma or degenerative pathology due to avascular property, low cell density and migratory ability. Discovery of novel therapeutic approaches for articular cartilage repair remains a significant clinical need. Hypoxia is a hallmark for cartilage development and pathology. Hypoxia inducible factor-1alpha (HIF-1α) has been identified as a key mediator for chondrocytes to response to fluctuations of oxygen availability during cartilage development or repair. This suggests that HIF-1α may serve as a target for modulating chondrocyte functions. In this study, using phenotypic cellular screen assays, we identify that Icariin, an active flavonoid component from Herba Epimedii, activates HIF-1α expression in chondrocytes. We performed systemic in vitro and in vivo analysis to determine the roles of Icariin in regulation of chondrogenesis. Our results show that Icariin significantly increases hypoxia responsive element luciferase reporter activity, which is accompanied by increased accumulation and nuclear translocation of HIF-1α in murine chondrocytes. The phenotype is associated with inhibiting PHD activity through interaction between Icariin and iron ions. The upregulation of HIF-1α mRNA levels in chondrocytes persists during chondrogenic differentiation for 7 and 14 days. Icariin (10−6 M) increases the proliferation of chondrocytes or chondroprogenitors examined by MTT, BrdU incorporation or colony formation assays. Icariin enhances chondrogenic marker expression in a micromass culture including Sox9, collagen type 2 (Col2α1) and aggrecan as determined by real-time PCR and promotes extracellular matrix (ECM) synthesis indicated by Alcian blue staining. ELISA assays show dramatically increased production of aggrecan and hydroxyproline in Icariin-treated cultures at day 14 of chondrogenic differentiation as compared with the controls. Meanwhile, the expression of chondrocyte catabolic marker genes

  5. 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

  6. Quantification of stiffness change in degenerated articular cartilage using optical coherence tomography-based air-jet indentation.

    PubMed

    Huang, Yan-Ping; Wang, Shu-Zhe; Saarakkala, Simo; Zheng, Yong-Ping

    2011-10-01

    Articular cartilage is a thin complex tissue that covers the bony ends of joints. Changes in the composition and structure of articular cartilage will cause degeneration, which may further lead to osteoarthritis. Decreased stiffness is one of the earliest symptoms of cartilage degeneration and also represents the imperfect quality of repaired cartilage. An optical coherence tomography (OCT)-based air-jet indentation system was recently developed in our group to measure the mechanical properties of soft tissues. In this study, this system was applied to quantify the change of mechanical properties of articular cartilage after degeneration induced by enzymatic digestions. Forty osteochondral disks (n = 20 × 2) were prepared from bovine patellae and treated with collagenase and trypsin digestions, respectively. The apparent stiffness of the cartilage was measured by the OCT-based air-jet indentation system before and after the degeneration. The results were also compared with those from a rigid contact mechanical indentation and an ultrasound water-jet indentation. Through the air-jet indentation, it was found that the articular cartilage stiffness dropped significantly by 84% (p < 0.001) and 63% (p < 0.001) on average after collagenase and trypsin digestions, respectively. The stiffness measured by the air-jet indentation system was highly correlated (R > 0.8, p < 0.001) with that from the other two indentation methods. This study demonstrated that the OCT-based air-jet indentation can be a useful tool to quantitatively assess the mechanical properties of articular cartilage, and this encourages us to further develop a miniaturized probe suitable for arthroscopic applications.

  7. Success rates and immunologic responses of autogenic, allogenic, and xenogenic treatments to repair articular cartilage defects.

    PubMed

    Revell, Christopher M; Athanasiou, Kyriacos A

    2009-03-01

    This review examines current approaches available for articular cartilage repair, not only in terms of their regeneration potential, but also as a function of immunologic response. Autogenic repair techniques, including osteochondral plug transplantation, chondrocyte implantation, and microfracture, are the most widely accepted clinical treatment options due to the lack of immunogenic reactions, but only moderate graft success rates have been reported. Although suspended allogenic chondrocytes are shown to evoke an immune response upon implantation, allogenic osteochondral plugs and tissue-engineered grafts using allogenic chondrocytes exhibit a tolerable immunogenic response. Additionally, these repair techniques produce neotissue with success rates approaching those of currently available autogenic repair techniques, while simultaneously obviating their major hindrance of donor tissue scarcity. To date, limited research has been performed with xenogenic tissue, although several studies demonstrate the potential for its long-term success. This article focuses on the various treatment options for cartilage repair and their associated success rates and immunologic responses.

  8. Success Rates and Immunologic Responses of Autogenic, Allogenic, and Xenogenic Treatments to Repair Articular Cartilage Defects

    PubMed Central

    Revell, Christopher M.

    2009-01-01

    This review examines current approaches available for articular cartilage repair, not only in terms of their regeneration potential, but also as a function of immunologic response. Autogenic repair techniques, including osteochondral plug transplantation, chondrocyte implantation, and microfracture, are the most widely accepted clinical treatment options due to the lack of immunogenic reactions, but only moderate graft success rates have been reported. Although suspended allogenic chondrocytes are shown to evoke an immune response upon implantation, allogenic osteochondral plugs and tissue-engineered grafts using allogenic chondrocytes exhibit a tolerable immunogenic response. Additionally, these repair techniques produce neotissue with success rates approaching those of currently available autogenic repair techniques, while simultaneously obviating their major hindrance of donor tissue scarcity. To date, limited research has been performed with xenogenic tissue, although several studies demonstrate the potential for its long-term success. This article focuses on the various treatment options for cartilage repair and their associated success rates and immunologic responses. PMID:19063664

  9. In vivo articular cartilage deformation: noninvasive quantification of intratissue strain during joint contact in the human knee

    PubMed Central

    Chan, Deva D.; Cai, Luyao; Butz, Kent D.; Trippel, Stephen B.; Nauman, Eric A.; Neu, Corey P.

    2016-01-01

    The in vivo measurement of articular cartilage deformation is essential to understand how mechanical forces distribute throughout the healthy tissue and change over time in the pathologic joint. Displacements or strain may serve as a functional imaging biomarker for healthy, diseased, and repaired tissues, but unfortunately intratissue cartilage deformation in vivo is largely unknown. Here, we directly quantified for the first time deformation patterns through the thickness of tibiofemoral articular cartilage in healthy human volunteers. Magnetic resonance imaging acquisitions were synchronized with physiologically relevant compressive loading and used to visualize and measure regional displacement and strain of tibiofemoral articular cartilage in a sagittal plane. We found that compression (of 1/2 body weight) applied at the foot produced a sliding, rigid-body displacement at the tibiofemoral cartilage interface, that loading generated subject- and gender-specific and regionally complex patterns of intratissue strains, and that dominant cartilage strains (approaching 12%) were in shear. Maximum principle and shear strain measures in the tibia were correlated with body mass index. Our MRI-based approach may accelerate the development of regenerative therapies for diseased or damaged cartilage, which is currently limited by the lack of reliable in vivo methods for noninvasive assessment of functional changes following treatment. PMID:26752228

  10. In vivo articular cartilage deformation: noninvasive quantification of intratissue strain during joint contact in the human knee

    NASA Astrophysics Data System (ADS)

    Chan, Deva D.; Cai, Luyao; Butz, Kent D.; Trippel, Stephen B.; Nauman, Eric A.; Neu, Corey P.

    2016-01-01

    The in vivo measurement of articular cartilage deformation is essential to understand how mechanical forces distribute throughout the healthy tissue and change over time in the pathologic joint. Displacements or strain may serve as a functional imaging biomarker for healthy, diseased, and repaired tissues, but unfortunately intratissue cartilage deformation in vivo is largely unknown. Here, we directly quantified for the first time deformation patterns through the thickness of tibiofemoral articular cartilage in healthy human volunteers. Magnetic resonance imaging acquisitions were synchronized with physiologically relevant compressive loading and used to visualize and measure regional displacement and strain of tibiofemoral articular cartilage in a sagittal plane. We found that compression (of 1/2 body weight) applied at the foot produced a sliding, rigid-body displacement at the tibiofemoral cartilage interface, that loading generated subject- and gender-specific and regionally complex patterns of intratissue strains, and that dominant cartilage strains (approaching 12%) were in shear. Maximum principle and shear strain measures in the tibia were correlated with body mass index. Our MRI-based approach may accelerate the development of regenerative therapies for diseased or damaged cartilage, which is currently limited by the lack of reliable in vivo methods for noninvasive assessment of functional changes following treatment.

  11. Chondrogenic Differentiation of Adipose-Derived Adult Stem Cells by a Porous Scaffold Derived from Native Articular Cartilage Extracellular Matrix

    PubMed Central

    Cheng, Nai-Chen; Estes, Bradley T.; Awad, Hani A.

    2009-01-01

    Adipose-derived adult stem cells (ASCs) have the ability to differentiate into a chondrogenic phenotype in response to specific environmental signals such as growth factors or artificial biomaterial scaffolds. In this study, we examined the hypothesis that a porous scaffold derived exclusively from articular cartilage can induce chondrogenesis of ASCs. Human ASCs were seeded on porous scaffolds derived from adult porcine articular cartilage and cultured in standard medium without exogenous growth factors. Chondrogenesis of ASCs seeded within the scaffold was evident by quantitative RT-PCR analysis for cartilage-specific extracellular matrix (ECM) genes. Histological and immunohistochemical examination showed abundant production of cartilage-specific ECM components—particularly, type II collagen—after 4 or 6 weeks of culture. After 6 weeks of culture, the cellular morphology in the ASC-seeded constructs resembled those in native articular cartilage tissue, with rounded cells residing in the glycosaminoglycan-rich regions of the scaffolds. Biphasic mechanical testing showed that the aggregate modulus of the ASC-seeded constructs increased over time, reaching 150 kPa by day 42, more than threefold higher than that of the unseeded controls. These results suggest that a porous scaffold derived from articular cartilage has the ability to induce chondrogenic differentiation of ASCs without exogenous growth factors, with significant synthesis and accumulation of ECM macromolecules, and the development of mechanical properties approaching those of native cartilage. These findings support the potential for a processed cartilage ECM as a biomaterial scaffold for cartilage tissue engineering. Additional in vivo evaluation is necessary to fully recognize the clinical implication of these observations. PMID:18950290

  12. Secretion of an articular cartilage proteoglycan-degrading enzyme activity by murine T lymphocytes in vitro.

    PubMed Central

    Kammer, G M; Sapolsky, A I; Malemud, C J

    1985-01-01

    Destruction of articular cartilage is the hallmark of inflammatory arthritides. Enzymes elaborated by mononuclear cells infiltrating the synovium mediate, in part, the degradation of the cartilage extracellular matrix. Since mononuclear cells are the dominant cell type found in chronic inflammatory synovitis, we investigated whether interaction of immune mononuclear cells with antigen initiated the synthesis and secretion of a proteoglycan-degrading enzyme activity. Proteoglycan-degrading enzyme activity was monitored by the capacity of murine spleen cell conditioned medium to release [3H]serine/35SO4 incorporated into rabbit cartilage proteoglycan monomer fraction (A1D1), and by the relative change in specific viscosity of bovine nasal cartilage proteoglycan monomer. The results demonstrated that both virgin and immune mononuclear cells spontaneously generated proteoglycan-degrading enzyme activity and that cellular activation and proliferation induced by the antigen keyhole limpet hemocyanin or the mitogen phytohemagglutinin was not required. Kinetic studies demonstrated stable release of the enzyme activity over 72 h. Cell separation studies showed that T lymphocytes, a thymoma line, and macrophages separately produced proteoglycan-degrading enzyme activity. The enzyme activity has been partially characterized and appears to belong to a class of neutral pH metal-dependent proteinases. These observations, the first to demonstrate that T lymphocytes secrete an enzyme capable of degrading cartilage proteoglycan, raise the possibility that this enzyme activity contributes to cartilage extracellular matrix destruction in vivo. Moreover, these data support the conclusion that production of this enzyme by T lymphocytes is independent of an antigen-specific stimulus. PMID:3897284

  13. The osteochondral ligament: a fibrous attachment between bone and articular cartilage in Rana catesbeiana.

    PubMed

    Felisbino, S L; Carvalho, H F

    2000-12-01

    The anuran epiphyseal cartilage shows a lateral expansion that covers the external surface of the bone, besides other features that distinguish it from the corresponding avian and mammalian structures. The fibrous structure that attaches the lateral cartilage to the bone was characterized in this work. It was designated osteochondral ligament (OCL) and presented two main areas. There was an inner area that was closer to the periosteal bone and contained a layer of osteoblasts and elongated cells aligned to and interspersed with thin collagen fibers. The thin processes of the cells in this area showed strong alkaline phosphatase activity. The outer area, which was closer to the cartilage, was rich in blood vessels and contained a few cells amongst thick collagen fibers. TRITC-phaloidin staining showed the cells of the inner area to be rich in F-actin, and were observed to form a net around the cell nucleus and to fill the cell processes which extended between the collagen fibers. Cells of the outer area were poor in actin cytoskeleton, while those associated with the blood vessels showed intense staining. Tubulin-staining was weak, regardless of the OCL region. The main fibers of the extracellular matrix in the OCL extended obliquely upwards from the cartilage to the bone. The collagen fibers inserted into the bone matrix as Sharpey's fibers and became progressively thicker as they made their way through the outer area to the cartilage. Immunocytochemistry showed the presence of type I and type III collagen. Microfibrils were found around the cells and amongst the collagen fibrils. These microfibrils were composed of either type VI collagen or fibrilin, as shown by immunocytochemistry. The results presented in this paper show that the osteochondral ligament of Rana catesbeiana is a complex and specialized fibrous attachment which guarantees a strong and flexible anchorage of the lateral articular cartilage to the periosteal bone shaft, besides playing a role in bone

  14. Articular cartilage tissue engineering with plasma-rich in growth factors and stem cells with nano scaffolds

    NASA Astrophysics Data System (ADS)

    Montaser, Laila M.; Abbassy, Hadeer A.; Fawzy, Sherin M.

    2016-09-01

    The ability to heal soft tissue injuries and regenerate cartilage is the Holy Grail of musculoskeletal medicine. Articular cartilage repair and regeneration is considered to be largely intractable due to the poor regenerative properties of this tissue. Due to their low self-repair ability, cartilage defects that result from joint injury, aging, or osteoarthritis, are the most often irreversible and are a major cause of joint pain and chronic disability. However, current methods do not perfectly restore hyaline cartilage and may lead to the apparition of fibro- or continue hypertrophic cartilage. The lack of efficient modalities of treatment has prompted research into tissue engineering combining stem cells, scaffold materials and environmental factors. The field of articular cartilage tissue engineering, which aims to repair, regenerate, and/or improve injured or diseased cartilage functionality, has evoked intense interest and holds great potential for improving cartilage therapy. Plasma-rich in growth factors (PRGF) and/or stem cells may be effective for tissue repair as well as cartilage regenerative processes. There is a great promise to advance current cartilage therapies toward achieving a consistently successful approach for addressing cartilage afflictions. Tissue engineering may be the best way to reach this objective via the use of stem cells, novel biologically inspired scaffolds and, emerging nanotechnology. In this paper, current and emergent approach in the field of cartilage tissue engineering is presented for specific application. In the next years, the development of new strategies using stem cells, in scaffolds, with supplementation of culture medium could improve the quality of new formed cartilage.

  15. Depth-dependent shear behavior of bovine articular cartilage: relationship to structure.

    PubMed

    Motavalli, Mostafa; Akkus, Ozan; Mansour, Joseph M

    2014-11-01

    The mechanical behavior of bovine articular cartilage in shear was measured and related to its structure through the depth of the tissue. To make these measurements, we designed an apparatus that could apply controlled shear displacement and measure the resulting shear force on cartilage specimens. Shear displacement and shear strain were obtained from confocal images of photobleached lines on fluorescently stained deformed samples. Depth-dependent collagen structure was obtained using compensated polarized light microscopy. Depth-dependent shear behavior and structure of samples from two animals were measured (group A and B). Both animals were 18-24 months old, which is the range in which they are expected reach skeletal maturity. In mature samples (group A), the stiffest region was located beneath the superficial zone, and the most compliant region was found in the radial zone. In contrast, in samples that were in the process of maturing (group B) the most compliant region was located in the superficial zone. Compensated polarized light microscopy suggested that the animal from which the group A samples were obtained was skeletally mature, whereas the animal yielding the group B samples was in the process of maturing. Compensated polarized light microscopy was an important adjunct to the mechanical shear behavior in that it provided a means to reconcile differences in observed shear behavior in mature and immature cartilage. Although samples were harvested from two animals, there were clear differences in structure and shear mechanical behavior. Differences in the depth-dependent shear strain were consistent with previous studies on mature and immature samples and, based on the structural variation between mature and immature articular cartilage, their mechanical behavior differences can be tenable. These results suggest that age, as well as species and anatomic location, need to be considered when reporting mechanical behavior results.

  16. 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.

  17. A Biosynthetic Scaffold that Facilitates Chondrocyte-Mediated Degradation and Promotes Articular Cartilage Extracellular Matrix Deposition

    PubMed Central

    Sridhar., Balaji V.; Dailing, Eric A.; Brock, J. Logan; Stansbury, Jeffrey W.; Randolph, Mark A.; Anseth, Kristi S.

    2015-01-01

    Articular cartilage remains a significant clinical challenge to repair because of its limited self-healing capacity. Interest has grown in the delivery of autologous chondrocytes to cartilage defects, and combining cell-based therapies with scaffolds that capture aspects of native tissue and allow cell-mediated remodeling could improve outcomes. Currently, scaffold-based therapies with encapsulated chondrocytes permit matrix production; however, resorption of the scaffold often does not match the rate of matrix production by chondrocytes, which can limit functional tissue regeneration. Here, we designed a hybrid biosynthetic system consisting of poly (ethylene glycol) (PEG) endcapped with thiols and crosslinked by norbornene-functionalized gelatin via a thiol-ene photopolymerization. The protein crosslinker was selected to facilitate chondrocyte-mediated scaffold remodeling and matrix deposition. Gelatin was functionalized with norbornene to varying degrees (~4–17 norbornenes/gelatin), and the shear modulus of the resulting hydrogels was characterized (<0.1–0.5 kPa). Degradation of the crosslinked PEG-gelatin hydrogels by chondrocyte-secreted enzymes was confirmed by gel permeation chromatography. Finally, chondrocytes encapsulated in these biosynthetic scaffolds showed significantly increased glycosaminoglycan deposition over just 14 days of culture, while maintaining high levels of viability and producing a distributed matrix. These results indicate the potential of a hybrid PEG-gelatin hydrogel to permit chondrocyte-mediated remodeling and promote articular cartilage matrix production. Tunable scaffolds that can easily permit chondrocyte-mediated remodeling may be useful in designing treatment options for cartilage tissue engineering applications. PMID:26900597

  18. Extraction techniques for the decellularization of tissue engineered articular cartilage constructs.

    PubMed

    Elder, Benjamin D; Eleswarapu, Sriram V; Athanasiou, Kyriacos A

    2009-08-01

    Several prior studies have been performed to determine the feasibility of tissue decellularization to create a non-immunogenic xenogenic tissue replacement for bladder, vasculature, heart valves, knee meniscus, temporomandibular joint disc, ligament, and tendon. However, limited work has been performed with articular cartilage, and no studies have examined the decellularization of tissue engineered constructs. The objective of this study was to assess the effects of different decellularization treatments on articular cartilage constructs, engineered using a scaffoldless approach, after 4wks of culture, using a two-phased approach. In the first phase, five different treatments were examined: 1) 1% SDS, 2) 2% SDS, 3) 2% Tributyl Phosphate, 4) 2% Triton X-100, and 5) Hypotonic followed by hypertonic solution. These treatments were applied for either 1h or 8h, followed by a 2h wash in PBS. Following this wash, the constructs were assessed histologically, biochemically for cellularity, GAG, and collagen content, and biomechanically for compressive and tensile properties. In phase II, the best treatment from phase I was applied for 1, 2, 4, 6, or 8h in order to optimize the application time. Treatment with 2% SDS for 1h or 2h significantly reduced the DNA content of the tissue, while maintaining the biochemical and biomechanical properties. On the other hand, 2% SDS for 6h or 8h resulted in complete histological decellularization, with complete elimination of cell nuclei on histological staining, although GAG content and compressive properties were significantly decreased. Overall, 2% SDS, for 1 or 2h, appeared to be the most effective agent for cartilage decellularization, as it resulted in decellularization while maintaining the functional properties. The results of this study are exciting as they indicate the feasibility of creating engineered cartilage that may be non-immunogenic as a replacement tissue.

  19. Chronic Changes in the Articular Cartilage and Meniscus Following Traumatic Impact to the Lapine Knee

    PubMed Central

    Fischenich, Kristine M.; Button, Keith D.; Coatney, Garrett A.; Fajardo, Ryan S.; Leikert, Kevin M.; Haut, Roger C.; Haut Donahue, Tammy L.

    2014-01-01

    The objective of this study was to induce anterior cruciate ligament (ACL) and meniscal damage, via a single tibiofemoral compressive impact, in order to document articular cartilage and meniscal changes post impact. Tibiofemoral joints of Flemish Giant rabbits were subjected to a single blunt impact that ruptured the ACL and produced acute meniscal damage. Animals were allowed unrestricted cage activity for 12 weeks before euthanasia. India ink analysis of the articular cartilage revealed higher degrees of surface damage on the impacted tibias (p=0.018) and femurs (p<0.0001) compared to controls. Chronic meniscal damage was most prevalent in the medial central and medial posterior regions. Mechanical tests revealed an overall 19.4% increase in tibial plateau cartilage thickness (p=0.026), 34.8% increase in tibial plateau permeability (p=0.054), 40.8% increase in femoral condyle permeability (p=0.029), and 20.1% decrease in femoral condyle matrix modulus (p=0.012) in impacted joints compared to controls. Both the instantaneous and equilibrium moduli of the lateral and medial menisci were decreased compared to control (p<0.02). Histological analyses revealed significantly increased presence of fissures in the medial femur (p = 0.036). In both the meniscus and cartilage there was a significant decrease in GAG coverage for the impacted limbs. Based on these results it is clear that an unattended combined meniscal and ACL injury results in significant changes to the soft tissues in this experimental joint 12 weeks post injury. Such changes are consistent with a clinical description of mid to late stage PTOA of the knee. PMID:25523754

  20. Duty Cycle of Deformational Loading Influences the Growth of Engineered Articular Cartilage.

    PubMed

    Ng, Kenneth W; Mauck, Robert L; Wang, Christopher C-B; Kelly, Terri-Ann N; Ho, Mandy M-Y; Chen, Faye Hui; Ateshian, Gerard A; Hung, Clark T

    2009-09-01

    This study examines how variations in the duty cycle (the duration of applied loading) of deformational loading can influence the mechanical properties of tissue engineered cartilage constructs over one month in bioreactor culture. Dynamic loading was carried out with three different duty cycles: 1 h on/1 h off for a total of 3 h loading/day, 3 h continuous loading, or 6 h of continuous loading per day, with all loading performed 5 days/week. All loaded groups showed significant increases in Young's modulus after one month (vs. free swelling controls), but only loading for a continuous 3 and 6 h showed significant increases in dynamic modulus by this time point. Histological analysis showed that dynamic loading can increase cartilage oligomeric matrix protein (COMP) and collagen types II and IX, as well as prevent the formation of a fibrous capsule around the construct. Type II and IX collagen deposition increased with increased with duration of applied loading. These results point to the efficacy of dynamic deformational loading in the mechanical preconditioning of engineered articular cartilage constructs. Furthermore, these results highlight the ability to dictate mechanical properties with variations in mechanical input parameters, and the possible importance of other cartilage matrix molecules, such as COMP, in establishing the functional material properties of engineered constructs.

  1. Articular Cartilage Optical Properties in the Spectral Range 300-850 nm.

    PubMed

    Ebert, D W; Roberts, C; Farrar, S K; Johnston, W M; Litsky, A S; Bertone, A L

    1998-07-01

    Measurements of absolute total reflectance were recorded from weight-bearing (n=9) and nonweight-bearing (n=9) equine articular cartilage specimens from 300 to 850 nm using a spectrophotometer with integrating sphere attachment. Following correction of measured spectra for interfacial reflections and edge losses, Kubelka-Munk theory was applied to estimate absorption and scattering coefficient, one-dimensional light intensity distribution, and light penetration depth. Kubelka-Munk absorption coefficients ranged from ∼7 cm-1 at 330 nm to ∼1 cm-1 at 850 nm. A localized absorption peak was noted at ∼340 nm. Above 510 nm, weight-bearing cartilage demonstrated significantly higher absorption coefficients than nonweight-bearing tissue (paired t-test, p<0.05). Kubelka-Munk scattering coefficients ranged from ∼40 cm-1 at 360 nm to ∼6 cm-1 at 850 nm. No statistical differences in scattering coefficient were noted between weight-bearing and nonweight-bearing tissue. Penetration depths predicted by Kubelka-Munk theory ranged from 0.6 mm at 350 nm to over 3 mm at 850 nm. Stronger absorption in weight-bearing cartilage compared to nonweight-bearing tissue resulted in lower light penetration depths in weight-bearing cartilage at all wavelengths longer than 510 nm. © 1998 Society of Photo-Optical Instrumentation Engineers.

  2. Articular cartilage optical properties in the spectral range 300--850 nm

    NASA Astrophysics Data System (ADS)

    Ebert, Daniel W.; Roberts, Cynthia J.; Farrar, Stuart K.; Johnston, William M.; Litsky, Alan S.; Bertone, Alicia L.

    1998-07-01

    Measurements of absolute total reflectance were recorded from weight-bearing (n equals 9) and nonweight-bearing (n equals 9) equine articular cartilage specimens from 300 to 850 nm using a spectrophotometer with integrating sphere attachment. Following correction of measured spectra for interfacial reflections and edge losses, Kubelka-Munk theory was applied to estimate absorption and scattering coefficient, 1D light intensity distribution, and light penetration depth. Kubelka-Munk absorption coefficients ranged from approximately 7 cm-1 at 330 nm to approximately 1 cm-1 at 850 nm. A localized absorption peak was noted at approximately 340 nm. Above 510 nm, weight-bearing cartilage demonstrated significantly higher absorption coefficients than nonweight-bearing tissue (paired t-test, p < 0.05). Kubelka-Munk scattering coefficients ranged from approximately 40 cm-1 at 360 nm to approximately 6 cm-1 at 850 nm. No statistical differences in scattering coefficient were noted between weight-bearing and nonweight-bearing tissue. Penetration depths predicted by Kubelka-Munk theory ranged from 0.6 mm at 350 nm to over 3 mm at 850 nm. Stronger absorption in weight-bearing cartilage compared to nonweight-bearing tissue resulted in lower light penetration depths in weight-bearing cartilage at all wavelengths longer than 510 nm.

  3. Structural characteristics of articular cartilage proteoglycan in IgG induced experimental immune synovitis.

    PubMed Central

    Malemud, C J; Yoo, J U; Goldberg, V M; Kresina, T F

    1987-01-01

    The early changes (five weeks) in the structure of newly synthesised and endogenous articular cartilage sulphated proteoglycans were studied in lapine IgG induced experimental immune synovitis. Rabbits with immune synovitis (IS-IgG) were compared with animals with a developed hypersensitivity to IgG (I-IgG) and with non-treated normal weight matched controls. Medial and lateral femoral condyle and tibial plateau cartilage was pooled and radiolabelled for 24 h in vitro with 35SO4. The samples constituted tissue from regions underlying pannus and from pannus free sites. Cartilage from animals with IS-IgG showed a significantly diminished amount of newly synthesised and endogenous proteoglycan aggregate and an increased amount of hydrodynamically small proteoglycans. Newly synthesised (obtained by in vivo radiosulphate labelling) and endogenous proteoglycans showed a similar profile. The proteoglycan monomer fraction from animals with IS-IgG failed to form proteoglycan aggregates in the presence of excess hyaluronic acid. In the group with IS-IgG linear regression analysis showed a statistically significant relationship between the synovial pathology scores (but not cartilage pathology score) and diminished newly synthesised and endogenous proteoglycan aggregate. PMID:3662640

  4. Development of a cellularly degradable PEG hydrogel to promote articular cartilage extracellular matrix deposition

    PubMed Central

    Sridhar, Balaji V.; Brock, J. Logan; Silver, Jason S.; Leight, Jennifer L.

    2015-01-01

    Healing articular cartilage remains a significant clinical challenge because of its limited self-healing capacity. While delivery of autologous chondrocytes to cartilage defects has received growing interest, combining cell-based therapies with scaffolds that capture aspects of native tissue and promote cell-mediated remodeling could improve outcomes. Currently, scaffold-based therapies with encapsulated chondrocytes permit matrix production; however, resorption of the scaffold does not match the rate of production by cells leading to generally low ECM outputs. Here, a PEG norbornene hydrogel was functionalized with thiolated TGF-β1 and crosslinked by an MMP-degradable peptide. Chondrocytes were co-encapsulated with a smaller population of MSCs, with the goal of stimulating matrix production and increasing bulk mechanical properties of the scaffold. Interestingly, the co-encapsulated cells cleaved the MMP-degradable target sequence more readily than either cell population alone. Relative to non-degradable gels, cellularly-degraded materials showed significantly increased GAG and collagen deposition over just 14 days of culture, while maintaining high levels of viability and producing a more diffuse matrix. These results indicate the potential of an enzymatically-degradable, peptide-functionalized PEG hydrogel to locally influence and promote cartilage matrix production over a short period. Scaffolds that permit cell-mediated remodeling may be useful in designing treatment options for cartilage tissue engineering applications. PMID:25607633

  5. Ultrastructural analysis of rat articular cartilage following treatment with dexamethasone and glycosaminoglycan-peptide complex.

    PubMed

    Annefeld, M; Erne, B; Rasser, Y

    1990-01-01

    This ultrastructural study describes a stereological analysis of rat articular cartilage, with and without exposure to dexamethasone and a chondroprotective drug used in the treatment of osteoarthritis. Normal rat cartilage was found to contain 27.6 x 10(4) chondrocytes/mm3 which occupied approximately 10% of the cartilage tissue, and the organelle content of each chondrocyte was calculated to be about 20% of the cytoplasmic volume. After 3 weeks of treatment with dexamethasone the chondrocytic volume was increased by 23% with a proportionate increase in the cellular volume of the whole cartilage, and in addition the organelle content was significantly reduced to about half that of the control chondrocytes. By contrast the administration of GP-C (RUMALON) to dexamethasone-treated animals reduced these steroid effects. No significant change was seen in the total chondrocyte numbers with either of the treatments. Whereas dexamethasone inhibits chondrocyte metabolism and produces concomitant ultrastructural changes, GP-C was found to counteract these effects, a result which supports the contention that GP-C helps to preserve chondrocyte function.

  6. Expression of extracellular matrix molecules typical of articular cartilage in the human scapholunate interosseous ligament.

    PubMed

    Milz, S; Aktas, T; Putz, R; Benjamin, M

    2006-06-01

    The scapholunate interosseous ligament (SLIL) connects the scaphoid and lunate bones and plays a crucial role in carpal kinematics. Its rupture leads to carpal instability and impairment of radiocarpal joint function. As the ligament is one of the first structures affected in rheumatoid arthritis, we conducted an immunohistochemical study of cadaveric tissue to determine whether it contains known autoantigens for rheumatoid arthritis. We immunolabelled the ligament from one hand in 12 cadavers with monoclonal antibodies directed against a wide range of extracellular matrix (ECM) molecules associated with both fibrous and cartilaginous tissues. The labelling profile has also enabled us to comment on how the molecular composition of the ligament relates to its mechanical function. All regions of the ligament labelled for types I, III and VI collagens, chondroitin 4 and 6 sulphates, keratan sulphate, dermatan sulphate, versican, tenascin and cartilage oligomeric matrix protein (COMP). However, both entheses labelled strongly for type II collagen, aggrecan and link protein and were distinctly fibrocartilaginous. In some regions, the ligament attached to bone via a region of hyaline cartilage that was continuous with articular cartilage. Labelling for cartilage molecules in the midsubstance was most evident dorsally. We conclude that the SLIL has an ECM which is typical of other highly fibrocartilaginous ligaments that experience both tensile load and shear. The presence of aggrecan, link protein, COMP and type II collagen could explain why the ligament may be a target for autoantigenic destruction in some forms of rheumatoid arthritis.

  7. Long-term storage and preservation of tissue engineered articular cartilage.

    PubMed

    Nover, Adam B; Stefani, Robert M; Lee, Stephanie L; Ateshian, Gerard A; Stoker, Aaron M; Cook, James L; Hung, Clark T

    2016-01-01

    With limited availability of osteochondral allografts, tissue engineered cartilage grafts may provide an alternative treatment for large cartilage defects. An effective storage protocol will be critical for translating this technology to clinical use. The purpose of this study was to evaluate the efficacy of the Missouri Osteochondral Allograft Preservation System (MOPS) for room temperature storage of mature tissue engineered grafts, focusing on tissue property maintenance during the current allograft storage window (28 days). Additional research compares MOPS to continued culture, investigates temperature influence, and examines longer-term storage. Articular cartilage constructs were cultured to maturity using adult canine chondrocytes, then preserved with MOPS at room temperature, in refrigeration, or kept in culture for an additional 56 days. MOPS storage maintained desired chondrocyte viability for 28 days of room temperature storage, retaining 75% of the maturity point Young's modulus without significant decline in biochemical content. Properties dropped past this time point. Refrigeration maintained properties similar to room temperature at 28 days, but proved better at 56 days. For engineered grafts, MOPS maintained the majority of tissue properties for the 28-day window without clearly extending that period as it had for native grafts. These results are the first evaluating engineered cartilage storage.

  8. Effect of low-power helium-neon laser irradiation on 13-week immobilized articular cartilage of rabbits.

    PubMed

    Bayat, Mohammad; Ansari, Anayatallah; Hekmat, Hossien

    2004-09-01

    Influence of low-power (632.8 nm, Helium-Neon, 13 J/cm2, three times a week) laser on 13-week immobilized articular cartilage was examined with rabbits knee model. Number of chondrocytes and depth of articular cartilage of experimental group were significantly higher than those of sham irradiated group. Surface morphology of sham-irradiated group had rough prominences, fibrillation and lacunae but surface morphology of experimental group had more similarities to control group than to sham irradiated group. There were marked differences between ultrastructure features of control group and experimental group in comparison with sham irradiated group. Low-power Helium-Neon laser irradiation on 13-week immobilized knee joints of rabbits neutrilized adverse effects of immobilization on articular cartilage.

  9. Canine articular cartilage regeneration using mesenchymal stem cells seeded on platelet rich fibrin

    PubMed Central

    Shams Asenjan, K.; Dehdilani, N.; Parsa, H.

    2017-01-01

    Objectives Mesenchymal stem cells have the ability to differentiate into various cell types, and thus have emerged as promising alternatives to chondrocytes in cell-based cartilage repair methods. The aim of this experimental study was to investigate the effect of bone marrow derived mesenchymal stem cells combined with platelet rich fibrin on osteochondral defect repair and articular cartilage regeneration in a canine model. Methods Osteochondral defects were created on the medial femoral condyles of 12 adult male mixed breed dogs. They were either treated with stem cells seeded on platelet rich fibrin or left empty. Macroscopic and histological evaluation of the repair tissue was conducted after four, 16 and 24 weeks using the International Cartilage Repair Society macroscopic and the O’Driscoll histological grading systems. Results were reported as mean and standard deviation (sd) and compared at different time points between the two groups using the Mann-Whitney U test, with a value < 0.05 considered statistically significant. Results Higher cumulative macroscopic and histological scores were observed in stem cell treated defects throughout the study period with significant differences noted at four and 24 weeks (9.25, sd 0.5 vs 7.25, sd 0.95, and 10, sd 0.81 vs 7.5, sd 0.57; p < 0.05) and 16 weeks (16.5, sd 4.04 vs 11, sd 1.15; p < 0.05), respectively. Superior gross and histological characteristics were also observed in stem cell treated defects. Conclusion The use of autologous culture expanded bone marrow derived mesenchymal stem cells on platelet rich fibrin is a novel method for articular cartilage regeneration. It is postulated that platelet rich fibrin creates a suitable environment for proliferation and differentiation of stem cells by releasing endogenous growth factors resulting in creation of a hyaline-like reparative tissue. Cite this article: D. Kazemi, K. Shams Asenjan, N. Dehdilani, H. Parsa. Canine articular cartilage regeneration using

  10. Parathyroid Hormone-Induced Bone Marrow Mesenchymal Stem Cell Chondrogenic Differentiation and its Repair of Articular Cartilage Injury in Rabbits

    PubMed Central

    Chen, Yushu; Chen, Yi; Zhang, Shujiang; Du, Xiufan; Bai, Bo

    2016-01-01

    Background We explored the effect of parathyroid hormone (PTH)-induced bone marrow stem cells (BMSCs) complexed with fibrin glue (FG) in the repair of articular cartilage injury in rabbits. Material/Methods Forty-eight rabbits randomized into four groups were subjected to articular surgery (cartilage loss). The PTH and non-PTH intervention groups included transplantation with PTH/BMSC/FG xenogeneic and BMSC/FG xenogeneic complexes, respectively, into the injured area. The injured group contained no transplant while the control group comprised rabbits without any articular injury. Samples were monitored for cartilage repair up to three months post-surgery. Immunohistochemistry as well as real-time fluorescent quantitative PCR and Western blot were used to analyze the expression of type II collagen and aggrecan in the repaired tissue. Results At 12 weeks post-surgery, the loss of articular cartilage in the PTH group was fully repaired by hyaline tissue. Typical cartilage lacunae and intact subchondral bone were found. The boundary separating the surrounding normal cartilage tissue disappeared. The gross and International Cartilage Repair Society (ICRS) histological ranking of the repaired tissue was significantly higher in the PTH intervention group than in the non-PTH intervention and injury groups (p<0.05) without any significant difference compared to the control group (p>0.05). Type II collagen and aggrecan stained positive and the average optical density, relative mRNA expression and protein-integrated optical density in the PTH group were higher than in non-PTH and injured groups (p<0.05) but not significantly different from the control group (p>0.05). Conclusions PTH/BMSC/FG xenogeneic complexes effectively repaired the loss of cartilage in rabbit knee injury. PMID:27847384

  11. A review of some recent developments in polarization-sensitive optical imaging techniques for the study of articular cartilage

    NASA Astrophysics Data System (ADS)

    Matcher, Stephen J.

    2009-05-01

    This article reviews recent developments in the optical imaging of articular cartilage using polarized-light methods, with an emphasis on tools that could be of use in tissue engineering approaches to treatment. Both second-harmonic generation microscopy and polarization-sensitive optical coherence tomography are described and their potential role in the treatment of cartilage disorders such as osteoarthritis is suggested. Key results are reviewed and future developments are discussed.

  12. Transport phenomena in articular cartilage cryopreservation as predicted by the modified triphasic model and the effect of natural inhomogeneities.

    PubMed

    Abazari, Alireza; Thompson, Richard B; Elliott, Janet A W; McGann, Locksley E

    2012-03-21

    Knowledge of the spatial and temporal distribution of cryoprotective agent (CPA) is necessary for the cryopreservation of articular cartilage. Cartilage dehydration and shrinkage, as well as the change in extracellular osmolality, may have a significant impact on chondrocyte survival during and after CPA loading, freezing, and thawing, and during CPA unloading. In the literature, Fick's law of diffusion is commonly used to predict the spatial distribution and overall concentration of the CPA in the cartilage matrix, and the shrinkage and stress-strain in the cartilage matrix during CPA loading are neglected. In this study, we used a previously described biomechanical model to predict the spatial and temporal distributions of CPA during loading. We measured the intrinsic inhomogeneities in initial water and fixed charge densities in the cartilage using magnetic resonance imaging and introduced them into the model as initial conditions. We then compared the prediction results with the results obtained using uniform initial conditions. The simulation results in this study demonstrate the presence of a significant mechanical strain in the matrix of the cartilage, within all layers, during CPA loading. The osmotic response of the chondrocytes to the cartilage dehydration during CPA loading was also simulated. The results reveal that a transient shrinking occurs to different levels, and the chondrocytes experience a significant decrease in volume, particularly in the middle and deep zones of articular cartilage, during CPA loading.

  13. 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

  14. Poly(dopamine) coating of scaffolds for articular cartilage tissue engineering.

    PubMed

    Tsai, Wei-Bor; Chen, Wen-Tung; Chien, Hsiu-Wen; Kuo, Wei-Hsuan; Wang, Meng-Jiy

    2011-12-01

    A surface modification technique based on poly(dopamine) deposition developed from oxidative polymerization of dopamine is known to promote cell adhesion to several cell-resistant substrates. In this study this technique was applied to articular cartilage tissue engineering. The adhesion and proliferation of rabbit chondrocytes were evaluated on poly(dopamine)-coated polymer films, such as polycaprolactone, poly(L-lactide), poly(lactic-co-glycolic acid) and polyurethane, biodegradable polymers that are commonly used in tissue engineering. Cell adhesion was significantly increased by merely 15 s of dopamine incubation, and 4 min incubation was enough to reach maximal cell adhesion, a 1.35-2.69-fold increase compared with that on the untreated substrates. Cells also grew much faster on the poly(dopamine)-coated substrates than on untreated substrates. The increase in cell affinity for poly(dopamine)-coated substrates was demonstrated via enhancement of the immobilization of serum adhesive proteins such as fibronectin. When the poly(dopamine)-coating technique was applied to three-dimensional (3-D) polyurethane scaffolds, the proliferation of chondrocytes and the secretion of glycosaminoglycans were increased compared with untreated scaffolds. Our results show that the deposition of a poly(dopamine) layer on 3-D porous scaffolds is a simple and promising strategy for articular cartilage tissue engineering, and may be applied to other types of tissue engineering.

  15. Hydromechanical stimulator for chondrocyte-seeded constructs in articular cartilage tissue engineering applications.

    PubMed

    Pourmohammadali, Homeyra; Chandrashekar, Naveen; Medley, John B

    2013-03-01

    Mechanical stimulation is a key technique used for controlling the mechanical properties of tissue engineered articular cartilage constructs proposed for defect repair. The present study introduces a new technical method and device for 'hydromechanical' stimulation of tissue engineered articular cartilage constructs. The stimulation consists of simultaneous cyclic compression, frictional shear from a sliding indenter contact and direct pressurized fluid perfusion. Each of these modes of mechanical loading has been shown by other research groups to effectively stimulate tissue engineered constructs. A device for applying these conditions was designed, developed and tested. Two sets (high and low perfusion flow rates) of three experiments were performed, each with two samples subjected to hydromechanical stimulation conditions (compression and friction forces along with perfusion). Two other samples from each set were subjected to just compression and dynamic frictional shear forces, and two more were used as controls (not stimulated). The average amount of glycosaminoglycan retained in the constructs after 3 weeks ranked from low to high as follows: controls, hydromechanical conditions with the low-flow rate, hydromechanical conditions with the high-flow rate and just compression plus dynamic frictional shear. Statistically significant differences were not detected. However, future studies would focus on glycosaminoglycan production in the superficial zone, measuring the glycosaminoglycan released to the nutrient media, and address altering the hydromechanical stimulation parameters using the results of the present study as guidance, in attempts to achieve statistically significant increases in glycosaminoglycan production compared with the controls.

  16. Mechanics and crack formation in the extracellular matrix with articular cartilage as a model system

    NASA Astrophysics Data System (ADS)

    Kearns, Sarah; Silverberg, Jesse; Bonassar, Lawrence; Cohen, Itai; Das, Moumita

    We investigate the mechanical structure-function relations in the extracellular matrix (ECM) with focus on crack formation and failure. As a model system, our study focuses on the ECM in articular cartilage (AC), the tissue that covers the ends of bones, and distributes load in joints including in the knees, shoulders, and hips. The strength, toughness, and crack resistance of native articular cartilage is unparalleled in materials made by humankind. This mechanical response is mainly due to its ECM. The ECM in AC has two major mechanobiological components: a network of the biopolymer collagen and a flexible aggrecan gel. We model this system as a biopolymer network embedded in a swelling gel, and investigate the conditions for the formation and propagation of cracks using a combination of rigidity percolation theory and energy minimization approaches. Our results may provide useful insights into the design principles of the ECM as well as of biomimetic hydrogels that are mechanically robust and can, at the same time, easily adapt to cues in their surroundings. This work was partially supported by a Cottrell College Science Award.

  17. Expression of collagen types I and II on articular cartilage in a rat knee contracture model.

    PubMed

    Hagiwara, Yoshihiro; Ando, Akira; Chimoto, Eiichi; Tsuchiya, Masahiro; Takahashi, Ichiro; Sasano, Yasuyuki; Onoda, Yoshito; Suda, Hideaki; Itoi, Eiji

    2010-01-01

    The purpose of our study was to clarify the expression patterns of collagen types I and II on articular cartilage after immobilization in a rat knee contracture model in 3 specific areas (noncontact area, transitional area, contact area). The unilateral knee joints of adult male rats were rigidly immobilized at 150 degrees of flexion using screws and a rigid plastic plate. Sham-operated animals had holes drilled in the femur and the tibia and screws inserted but were not plated. The expression patterns of collagen types I and II in each area were evaluated by in situ hybridization (ISH), immunohistochemistry (IHC), and quantitative real-time polymerase chain reaction (qPCR). The expression of collagen type II in the noncontact area was decreased by ISH but appeared unchanged when examined by IHC. In the transitional and contact areas, the expression of collagen type II was initially shown to have decreased and then increased at the hypertrophic chondrocytes by ISH but appeared decreased by IHC. Quantitative PCR revealed the decreased expression of type II collagen in the contact area. Immunostaining of collagen type I was increased at the noncontact area and transitional areas. Alterations of collagen types I and II expression may also affect the degeneration of articular cartilage after immobilization and the changes were different in the three areas.

  18. The effect of collagen fibril orientation on the biphasic mechanics of articular cartilage.

    PubMed

    Meng, Qingen; An, Shuqiang; Damion, Robin A; Jin, Zhongmin; Wilcox, Ruth; Fisher, John; Jones, Alison

    2017-01-01

    The highly inhomogeneous distribution of collagen fibrils may have important effects on the biphasic mechanics of articular cartilage. However, the effect of the inhomogeneity of collagen fibrils has mainly been investigated using simplified three-layered models, which may have underestimated the effect of collagen fibrils by neglecting their realistic orientation. The aim of this study was to investigate the effect of the realistic orientation of collagen fibrils on the biphasic mechanics of articular cartilage. Five biphasic material models, each of which included a different level of complexity of fibril reinforcement, were solved using two different finite element software packages (Abaqus and FEBio). Model 1 considered the realistic orientation of fibrils, which was derived from diffusion tensor magnetic resonance images. The simplified three-layered orientation was used for Model 2. Models 3-5 were three control models. The realistic collagen orientations obtained in this study were consistent with the literature. Results from the two finite element implementations were in agreement for each of the conditions modelled. The comparison between the control models confirmed some functions of collagen fibrils. The comparison between Models 1 and 2 showed that the widely-used three-layered inhomogeneous model can produce similar fluid load support to the model including the realistic fibril orientation; however, an accurate prediction of the other mechanical parameters requires the inclusion of the realistic orientation of collagen fibrils.

  19. Chondrocytes, Mesenchymal Stem Cells, and Their Combination in Articular Cartilage Regenerative Medicine.

    PubMed

    Nazempour, A; Van Wie, B J

    2016-05-01

    Articular cartilage (AC) is a highly organized connective tissue lining, covering the ends of bones within articulating joints. Its highly ordered structure is essential for stable motion and provides a frictionless surface easing load transfer. AC is vulnerable to lesions and, because it is aneural and avascular, it has limited self-repair potential which often leads to osteoarthritis. To date, no fully successful treatment for osteoarthritis has been reported. Thus, the development of innovative therapeutic approaches is desperately needed. Autologous chondrocyte implantation, the only cell-based surgical intervention approved in the United States for treating cartilage defects, has limitations because of de-differentiation of articular chondrocytes (AChs) upon in vitro expansion. De-differentiation can be abated if initial populations of AChs are co-cultured with mesenchymal stem cells (MSCs), which not only undergo chondrogenesis themselves but also support chondrocyte vitality. In this review we summarize studies utilizing AChs, non-AChs, and MSCs and compare associated outcomes. Moreover, a comprehensive set of recent human studies using chondrocytes to direct MSC differentiation, MSCs to support chondrocyte re-differentiation and proliferation in co-culture environments, and exploratory animal intra- and inter-species studies are systematically reviewed and discussed in an innovative manner allowing side-by-side comparisons of protocols and outcomes. Finally, a comprehensive set of recommendations are made for future studies.

  20. 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

  1. Vulnerability of the Superficial Zone of Immature Articular Cartilage to Compressive Injury

    SciTech Connect

    Rolauffs, R.; Muehleman, C; Li, J; Kurz, B; Kuettner, K; Frank, E; Grodzinsky, A

    2010-01-01

    The zonal composition and functioning of adult articular cartilage causes depth-dependent responses to compressive injury. In immature cartilage, shear and compressive moduli as well as collagen and sulfated glycosaminoglycan (sGAG) content also vary with depth. However, there is little understanding of the depth-dependent damage caused by injury. Since injury to immature knee joints most often causes articular cartilage lesions, this study was undertaken to characterize the zonal dependence of biomechanical, biochemical, and matrix-associated changes caused by compressive injury. Disks from the superficial and deeper zones of bovine calves were biomechanically characterized. Injury to the disks was achieved by applying a final strain of 50% compression at 100%/second, followed by biomechanical recharacterization. Tissue compaction upon injury as well as sGAG density, sGAG loss, and biosynthesis were measured. Collagen fiber orientation and matrix damage were assessed using histology, diffraction-enhanced x-ray imaging, and texture analysis. Injured superficial zone disks showed surface disruption, tissue compaction by 20.3 {+-} 4.3% (mean {+-} SEM), and immediate biomechanical impairment that was revealed by a mean {+-} SEM decrease in dynamic stiffness to 7.1 {+-} 3.3% of the value before injury and equilibrium moduli that were below the level of detection. Tissue areas that appeared intact on histology showed clear textural alterations. Injured deeper zone disks showed collagen crimping but remained undamaged and biomechanically intact. Superficial zone disks did not lose sGAG immediately after injury, but lost 17.8 {+-} 1.4% of sGAG after 48 hours; deeper zone disks lost only 2.8 {+-} 0.3% of sGAG content. Biomechanical impairment was associated primarily with structural damage. The soft superficial zone of immature cartilage is vulnerable to compressive injury, causing superficial matrix disruption, extensive compaction, and textural alteration, which results

  2. Healing results in meniscus and articular cartilage photochemically welded with 1,8-naphthalimide dyes

    NASA Astrophysics Data System (ADS)

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

    1997-05-01

    Meniscal tears and partial thickness defects in articular cartilage do not heal spontaneously. In this paper results are described of studies of a procedure for evoking the healing response in such lesions by a non-thermal tissue sparing photochemical weld using 1,8-naphthalimide dyes. Fifteen essentially mature Barbados sheep 40 - 60 pounds in weight received a 2 - 3 mm flap tear by incision in the red white zone of the medial meniscus oriented parallel to the table of the tibia. The animals were divided into four groups; Group I, no treatment; Group II, treatment by laser activated photoactive dyes; Group III, treatment by suturing; Group IV, treatment by laser irradiation only; Group V, treatment by photoactive dyes only. In another group of 12 sheep partial thickness flap tear was created by incision in the articular cartilage of the femoral condyle. These were divided into four groups as for the meniscus study, omitting the sutured control. Welds were made using the dimeric dye MBM Gold BW 012-012-012 at 12 mM in PBS, 457.9 nm argon ion laser radiation at 800 mW/cm2, 7.5 minutes (360 J/cm2) with approximately 2 kg/cm2 externally applied pressure. Animals were sacrificed at 24 hr, 4 weeks, 3 and 6 months postoperatively. Gross appearance of menisci and cartilage in all welded knees was normal and all welds resisted deformation or loosening under forceful probing. Histology of studies of both tissues out to 6 moths disclosed close bonding of welded area, continuing healing response in the form of cellular recruitment and protein deposition and the absence of inflammatory response. Tissue erosion and arthritic changes were evident in all unwelded controls.

  3. Biochemical and biomechanical alterations in equine articular cartilage following an experimentally-induced synovitis.

    PubMed

    Palmer, J L; Bertone, A L; Malemud, C J; Mansour, J

    1996-06-01

    The effects of inflammation on the biochemical and biomechanical properties of articular cartilage at two sites (dorsal and palmar) from the radial facet of the equine third carpal bone were examined in response to a synovitis induced with Escherichia coli lipopolysaccharide (LPS). Four groups were studied. In group 1 synovitis was induced at time zero and evaluated at week 6. Group 2 was the sham-treated control for group 1. In group 3 synovitis was induced at time zero and evaluated at week 2. Group 4 was the sham-treated control for group 3. There was a significant increase (P < 0.05) in newly synthesized proteoglycan PG from both sites in group 3 as compared to the sham-treated groups and group 1. No significant difference in the endogenous PG concentration between groups or sites was detected. Sepharose CL-2B revealed two peaks of newly synthesized PG in all groups; an early peak (Kav 0.11-0.13) and a late peak (Kav 0.48-0.64). Newly synthesized PG profiles from sham-treated groups and group 3 were similar, but the group 3 PG profile exhibited a more pronounced early peak. Conversely, the PG profile from group 1 demonstrated a more prominent late peak. Electrophoresis and Western blot analysis of the pooled late PG peak fractions from the sham-treated and group 1 showed a single toluidine blue stained band from both sites which reacted with monoclonal antibody (MAb) 1C6. By contrast, the late peak from the palmar site in group 3 showed an additional faster moving component on composite gels which did not react with MAb 1C6. There was a significant decrease in Poisson's ratio and a significant increase in cartilage thickness in groups 1 and 3 which had received synovitis. The increase in cartilage thickness of groups 1 and 3 was also significantly affected by site (dorsal > palmar). There was no significant difference in aggregate modulus or permeability constant among groups. Primary joint inflammation induced by LPS alters the biochemical and biomechanical

  4. Second-harmonic and two-photon imaging and polarimetry of articular cartilage

    NASA Astrophysics Data System (ADS)

    Mansfield, Jessica; Winlove, C. Peter; Moger, Julian; Knapp, Karen; Matcher, Steve

    2007-02-01

    Articular cartilage possesses an extensive extracellular matrix consisting of a highly organised network of collagen fibres embedded in a much finer mesh of proteoglycans and other glycoproteins. Many fundamental issues of cartilage biomechanics, its ageing and the development of osteoarthritis concern the detailed organisation of this matrix. Here we investigate the application of multi-photon microscopy to characterise the structure of the extracellular matrix. In reflection mode both second harmonic Generation (SHG) and two photon fluorescence (TPF) imaging modalities reveal differences in the pericellular and inter-territorial matrix in normal tissue and additional changes in degenerative lesions. The SHG signal from the surface zone is dependent on the direction of polarization of the laser excitation beam but the TPF signal is not. The former can be quantified to determine fibre orientation although the pattern is less well resolved than in tendon, reflecting the less regular orientation of the finer fibres. Nevertheless, previously unreported subtle variations in fibre orientation over the surface of the cartilage can be observed. In order to characterise variations with depth we carried out polarization sensitivity experiments at depths up to 180 microns into the tissue. At greater depths the polarization sensitivity is affected by the birefringence and dichroism of the overlying tissue and we have quantified these effects to allow correction of the data.

  5. The structure and function of the pericellular matrix of articular cartilage.

    PubMed

    Wilusz, Rebecca E; Sanchez-Adams, Johannah; Guilak, Farshid

    2014-10-01

    Chondrocytes in articular cartilage are surrounded by a narrow pericellular matrix (PCM) that is both biochemically and biomechanically distinct from the extracellular matrix (ECM) of the tissue. While the PCM was first observed nearly a century ago, its role is still under investigation. In support of early hypotheses regarding its function, increasing evidence indicates that the PCM serves as a transducer of biochemical and biomechanical signals to the chondrocyte. Work over the past two decades has established that the PCM in adult tissue is defined biochemically by several molecular components, including type VI collagen and perlecan. On the other hand, the biomechanical properties of this structure have only recently been measured. Techniques such as micropipette aspiration, in situ imaging, computational modeling, and atomic force microscopy have determined that the PCM exhibits distinct mechanical properties as compared to the ECM, and that these properties are influenced by specific PCM components as well as disease state. Importantly, the unique relationships among the mechanical properties of the chondrocyte, PCM, and ECM in different zones of cartilage suggest that this region significantly influences the stress-strain environment of the chondrocyte. In this review, we discuss recent advances in the measurement of PCM mechanical properties and structure that further increase our understanding of PCM function. Taken together, these studies suggest that the PCM plays a critical role in controlling the mechanical environment and mechanobiology of cells in cartilage and other cartilaginous tissues, such as the meniscus or intervertebral disc.

  6. Linking Cellular and Mechanical Processes in Articular Cartilage Lesion Formation: A Mathematical Model

    PubMed Central

    Kapitanov, Georgi I.; Wang, Xiayi; Ayati, Bruce P.; Brouillette, Marc J.; Martin, James A.

    2016-01-01

    Post-traumatic osteoarthritis affects almost 20% of the adult US population. An injurious impact applies a significant amount of physical stress on articular cartilage and can initiate a cascade of biochemical reactions that can lead to the development of osteoarthritis. In our effort to understand the underlying biochemical mechanisms of this debilitating disease, we have constructed a multiscale mathematical model of the process with three components: cellular, chemical, and mechanical. The cellular component describes the different chondrocyte states according to the chemicals these cells release. The chemical component models the change in concentrations of those chemicals. The mechanical component contains a simulation of a blunt impact applied onto a cartilage explant and the resulting strains that initiate the biochemical processes. The scales are modeled through a system of partial-differential equations and solved numerically. The results of the model qualitatively capture the results of laboratory experiments of drop-tower impacts on cartilage explants. The model creates a framework for incorporating explicit mechanics, simulated by finite element analysis, into a theoretical biology framework. The effort is a step toward a complete virtual platform for modeling the development of post-traumatic osteoarthritis, which will be used to inform biomedical researchers on possible non-invasive strategies for mitigating the disease. PMID:27843894

  7. Effects of refrigeration and freezing on the electromechanical and biomechanical properties of articular cartilage.

    PubMed

    Changoor, Adele; Fereydoonzad, Liah; Yaroshinsky, Alex; Buschmann, Michael D

    2010-06-01

    In vitro electromechanical and biomechanical testing of articular cartilage provide critical information about the structure and function of this tissue. Difficulties obtaining fresh tissue and lengthy experimental testing procedures often necessitate a storage protocol, which may adversely affect the functional properties of cartilage. The effects of storage at either 4°C for periods of 6 days and 12 days, or during a single freeze-thaw cycle at -20°C were examined in young bovine cartilage. Non-destructive electromechanical measurements and unconfined compression testing on 3 mm diameter disks were used to assess cartilage properties, including the streaming potential integral (SPI), fibril modulus (Ef), matrix modulus (Em), and permeability (k). Cartilage disks were also examined histologically. Compared with controls, significant decreases in SPI (to 32.3±5.5% of control values, p<0.001), Ef (to 31.3±41.3% [corrected] of control values, p=0.046), Em (to 6.4±8.5% of control values, p<0.0001), and an increase in k (to 2676.7±2562.0% of control values, p=0.004) were observed at day 12 of refrigeration at 4°C, but no significant changes were detected at day 6. A trend toward detecting a decrease in SPI (to 94.2±6.2% of control values, p=0.083) was identified following a single freeze-thaw cycle, but no detectable changes were observed for any biomechanical parameters. All numbers are mean±95% confidence interval. These results indicate that fresh cartilage can be stored in a humid chamber at 4°C for a maximum of 6 days with no detrimental effects to cartilage electromechanical and biomechanical properties, while one freeze-thaw cycle produces minimal deterioration of biomechanical and electromechanical properties. A comparison to literature suggested that particular attention should be paid to the manner in which specimens are thawed after freezing, specifically by minimizing thawing time at higher temperatures.

  8. Functional adaptation of equine articular cartilage: the formation of regional biochemical characteristics up to age one year.

    PubMed

    Brama, P A; Tekoppele, J M; Bank, R A; Barneveld, A; van Weeren, P R

    2000-05-01

    Biochemical heterogeneity of cartilage within a joint is well known in mature individuals. It has recently been reported that heterogeneity for proteoglycan content and chondrocyte metabolism in sheep develops postnatally under the influence of loading. No data exist on the collagen network in general or on the specific situation in the horse. The objective of this study was to investigate the alterations in equine articular cartilage biochemistry that occur from birth up to age one year, testing the hypothesis that the molecular composition of equine cartilage matrix is uniform at birth and biochemical heterogeneity is formed postnatally. Water content, DNA content, glycosaminoglycan content (GAG) and biochemical characteristics of the collagen network (collagen content, hydroxylysine content and hydroxylysylpyridinoline [HP] crosslinks) were measured in immature articular cartilage of neonatal (n = 16), 5-month-old foals (n = 16) and yearlings (n = 16) at 2 predefined differently loaded sites within the metacarpophalangeal joint. Statistical differences between sites were analysed by ANOVA (P<0.01), and age correlation was tested by Pearson's product moment correlation analysis (P<0.01). In neonatal cartilage no significant site differences were found for any of the measured biochemical parameters. This revealed that the horse has a biochemically uniform joint (i.e. the cartilage) at birth. In the 5-month-old foals and yearlings, significant site differences, comparable to those in the mature horse, were found for DNA, GAG, collagen content and hydroxylysine content. This indicates that functional adaptation of articular cartilage to weight bearing for these biochemical parameters takes place during the first months postpartum. Water content and HP crosslinks showed no difference between the 2 sites from neonatal horses, 5-month-old animals and yearlings. At both sites water, DNA and GAG decreased during maturation while collagen content, hydroxylysine content

  9. The Healing Effect of Adipose-Derived Mesenchymal Stem Cells in Full-thickness Femoral Articular Cartilage Defects of Rabbit

    PubMed Central

    Mehrabani, D.; Babazadeh, M.; Tanideh, N.; Zare, S.; Hoseinzadeh, S.; Torabinejad, S.; Koohi-Hosseinabadi, O.

    2015-01-01

    Background: Articular cartilage defect can lead to degradation of subchondral bone and osteoarthritis (OA). Objective: To determine the healing effect of transplantation of adipose-derived mesenchymal stem cells (Ad-MSCs) in full-thickness femoral articular cartilage defects in rabbit. Methods: 12 rabbits were equally divided into cell-treated and control groups. In cell-treated group, 2×106 cells of third passage suspended in 1 mL of DMEM was injected into articular defect. The control group just received 1 mL of DMEM. Dulbecco’s modified Eagles medium (DMEM) supplemented with 10% fetal bovine serum (FBS), 1% penicillin and streptomycin and 2 mM L-glutamine were used for cell culture. To induce cartilage defect, 4 mm articular cartilage full-thickness defect was created in the knee. For histological evaluation in each group (H&E, safranin-O and toluidine blue), 3 rabbits were sacrificed 4 weeks and 3 animals, 8 weeks after cell transplantation. Results: In cell therapy group post-transplantation, no abnormal gross findings were noticed. Neo-formed tissues in cell-treated groups were translucent with a smooth and intact surface and less irregularity. In cell-treated group after 8 weeks post-transplantation, the overall healing score of experimental knees were superior when compared to other groups. Conclusion: We showed that Ad-MSCs, as an available and non-invasive produced source of cells, could be safely administered in knee osteochondral defects. PMID:26576262

  10. 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

  11. Comparative analysis of gene expression profiles of hip articular cartilage between non-traumatic necrosis and osteoarthritis.

    PubMed

    Wang, Wenyu; Liu, Yang; Hao, Jingcan; Zheng, Shuyu; Wen, Yan; Xiao, Xiao; He, Awen; Fan, Qianrui; Zhang, Feng; Liu, Ruiyu

    2016-10-10

    Hip cartilage destruction is consistently observed in the non-traumatic osteonecrosis of femoral head (NOFH) and accelerates its bone necrosis. The molecular mechanism underlying the cartilage damage of NOFH remains elusive. In this study, we conducted a systematically comparative study of gene expression profiles between NOFH and osteoarthritis (OA). Hip articular cartilage specimens were collected from 12 NOFH patients and 12 controls with traumatic femoral neck fracture for microarray (n=4) and quantitative real-time PCR validation experiments (n=8). Gene expression profiling of articular cartilage was performed using Agilent Human 4×44K Microarray chip. The accuracy of microarray experiment was further validated by qRT-PCR. Gene expression results of OA hip cartilage were derived from previously published study. Significance Analysis of Microarrays (SAM) software was applied for identifying differently expressed genes. Gene ontology (GO) and pathway enrichment analysis were conducted by Gene Set Enrichment Analysis software and DAVID tool, respectively. Totally, 27 differently expressed genes were identified for NOFH. Comparing the gene expression profiles of NOFH cartilage and OA cartilage detected 8 common differently expressed genes, including COL5A1, OGN, ANGPTL4, CRIP1, NFIL3, METRNL, ID2 and STEAP1. GO comparative analysis identified 10 common significant GO terms, mainly implicated in apoptosis and development process. Pathway comparative analysis observed that ECM-receptor interaction pathway and focal adhesion pathway were enriched in the differently expressed genes of both NOFH and hip OA. In conclusion, we identified a set of differently expressed genes, GO and pathways for NOFH articular destruction, some of which were also involved in the hip OA. Our study results may help to reveal the pathogenetic similarities and differences of cartilage damage of NOFH and hip OA.

  12. Topographical variations in articular cartilage and subchondral bone of the normal rat knee are age-related.

    PubMed

    Hamann, Nina; Brüggemann, Gert-Peter; Niehoff, Anja

    2014-09-01

    In osteoarthritis animal models the rat knee is one of the most frequently investigated joint. However, it is unknown whether topographical variations in articular cartilage and subchondral bone of the normal rat knee exist and how they are linked or influenced by growth and maturation. Detailed knowledge is needed in order to allow interpretation and facilitate comparability of published osteoarthritis studies. For the first time, the present study maps topographical variations in cartilage thickness, cartilage compressive properties and subchondral bone microarchitecture between the medial and lateral tibial compartment of normal growing rat knees (7 vs. 13 weeks). Thickness and compressive properties (aggregate modulus) of cartilage were determined and the subchondral bone was analyzed by micro-computed tomography. We found that articular cartilage thickness is initially homogenous in both compartments, but then differentiates during growth and maturation resulting in greater cartilage thickness in the medial compartment in the 13-week-old animals. Cartilage compressive properties did not vary between the two sites independently of age. In both age-groups, subchondral plate thickness as well as trabecular bone volume ratio and trabecular thickness were greater in the medial compartment. While a high porosity of subchondral bone plate with a high topographical variation (medial/lateral) could be observed in the 7-week-old animals, the porosity was reduced and was accompanied by a reversion in topographical variation when reaching maturity. Our findings highlight that there is a considerable topographical variation in articular cartilage and subchondral bone within the normal rat knee in relation to the developmental status.

  13. Mesenchymal stem cells in regenerative medicine: Focus on articular cartilage and intervertebral disc regeneration.

    PubMed

    Richardson, Stephen M; Kalamegam, Gauthaman; Pushparaj, Peter N; Matta, Csaba; Memic, Adnan; Khademhosseini, Ali; Mobasheri, Reza; Poletti, Fabian L; Hoyland, Judith A; Mobasheri, Ali

    2016-04-15

    Musculoskeletal disorders represent a major cause of disability and morbidity globally and result in enormous costs for health and social care systems. Development of cell-based therapies is rapidly proliferating in a number of disease areas, including musculoskeletal disorders. Novel biological therapies that can effectively treat joint and spine degeneration are high priorities in regenerative medicine. Mesenchymal stem cells (MSCs) isolated from bone marrow (BM-MSCs), adipose tissue (AD-MSCs) and umbilical cord (UC-MSCs) show considerable promise for use in cartilage and intervertebral disc (IVD) repair. This review article focuses on stem cell-based therapeutics for cartilage and IVD repair in the context of the rising global burden of musculoskeletal disorders. We discuss the biology MSCs and chondroprogenitor cells and specifically focus on umbilical cord/Wharton's jelly derived MSCs and examine their potential for regenerative applications. We also summarize key components of the molecular machinery and signaling pathways responsible for the control of chondrogenesis and explore biomimetic scaffolds and biomaterials for articular cartilage and IVD regeneration. This review explores the exciting opportunities afforded by MSCs and discusses the challenges associated with cartilage and IVD repair and regeneration. There are still many technical challenges associated with isolating, expanding, differentiating, and pre-conditioning MSCs for subsequent implantation into degenerate joints and the spine. However, the prospect of combining biomaterials and cell-based therapies that incorporate chondrocytes, chondroprogenitors and MSCs leads to the optimistic view that interdisciplinary approaches will lead to significant breakthroughs in regenerating musculoskeletal tissues, such as the joint and the spine in the near future.

  14. Suppression of glycosaminoglycan synthesis by articular cartilage, but not of hyaluronic acid synthesis by synovium, after exposure to radiation

    SciTech Connect

    Hugenberg, S.T.; Myers, S.L.; Brandt, K.D.

    1989-04-01

    We recently found that injection of 2 mCi of yttrium 90 (90Y; approximately 23,000 rads) into normal canine knees stimulated glycosaminoglycan (GAG) synthesis by femoral condylar cartilage. The present investigation was conducted to determine whether radiation affects cartilage metabolism directly. Rates of GAG synthesis and degradation in normal canine articular cartilage were studied following irradiation. Cultured synovium from the same knees was treated similarly, to determine the effects of irradiation on hyaluronic acid synthesis. Twenty-four hours after exposure to 1,000 rads, 10,000 rads, or 50,000 rads, 35S-GAG synthesis by the cartilage was 93%, 69%, and 37%, respectively, of that in control, nonirradiated cartilage. The effect was not rapidly reversible: 120 hours after exposure to 50,000 rads, GAG synthesis remained at only 28% of the control level. Autoradiography showed marked suppression of 35S uptake by chondrocytes after irradiation. Cartilage GAG degradation was also increased following irradiation: 4 hours and 8 hours after exposure to 50,000 rads, the cartilage GAG concentration was only 66% and 54%, respectively, of that at time 0, while corresponding values for control, nonirradiated cartilage were 90% and 87%. In contrast to its effects on cartilage GAG metabolism, radiation at these levels had no effect on synovial hyaluronic acid synthesis.

  15. The mode of action of a glycosaminoglycan-peptide-complex (Rumalon) on articular cartilage of the rat in vivo.

    PubMed

    Annefeld, M; Erne, B

    1987-09-01

    Quantitative ultrastructural morphometry and autoradiography of articular cartilage were used to assess in 3 months old rats the effects of in vivo administration of dexamethasone alone or in combination with a glycosaminglycan-peptide-complex (GAGPC). Dexamethasone treatment (3 mg/kg week for three weeks) induced a decrease of 35S-sulphate incorporation in cartilage and ultrastructural changes of articular chondrocytes, mainly characterized by an increase in cell mortality rate, a decrease in length of endoplasmic reticulum, in the number of Golgi bodies and in mitochondrial pool and size. These autoradiographic and ultrastructural changes were reversed or prevented when GAGPC was administered concomitantly with dexamethasone. These results show that the modifications measured by quantitative ultrastructural morphometry of chondrocytes are consistent with changes in biosynthetic functions and that the GAGPC protects cartilage from the inhibitory effects of corticoids.

  16. Spatially localized structure-function relations in the elastic properties of sheared articular cartilage

    NASA Astrophysics Data System (ADS)

    Silverberg, Jesse; Bonassar, Lawrence; Cohen, Itai

    2013-03-01

    Contemporary developments in therapeutic tissue engineering have been enabled by basic research efforts in the field of biomechanics. Further integration of technology in medicine requires a deeper understanding of the mechanical properties of soft biological materials and the structural origins of their response under extreme stresses and strains. Drawing on the science generated by the ``Extreme Mechanics'' community, we present experimental results on the mechanical properties of articular cartilage, a hierarchically structured soft biomaterial found in the joints of mammalian long bones. Measurements of the spatially localized structure and mechanical properties will be compared with theoretical descriptions based on networks of deformed rods, poro-visco-elasticity, and standard continuum models. Discrepancies between experiment and theory will be highlighted, and suggestions for how models can be improved will be given.

  17. Nonlinear mechanical response of the extracellular matrix: learning from articular cartilage

    NASA Astrophysics Data System (ADS)

    Kearns, Sarah; Das, Moumita

    2015-03-01

    We study the mechanical structure-function relations in the extracellular matrix (ECM) with focus on nonlinear shear and compression response. As a model system, our study focuses on the ECM in articular cartilage tissue which has two major mechanobiological components: a network of the biopolymer collagen that acts as a stiff, reinforcing matrix, and a flexible aggrecan network that facilitates deformability. We model this system as a double network hydrogel made of interpenetrating networks of stiff and flexible biopolymers respectively. We study the linear and nonlinear mechanical response of the model ECM to shear and compression forces using a combination of rigidity percolation theory and energy minimization approaches. Our results may provide useful insights into the design principles of the ECM as well as biomimetic hydrogels that are mechanically robust and can, at the same time, easily adapt to cues in their surroundings.

  18. Regenerating cartilages by engineered ASCs: prolonged TGF-β3/BMP-6 expression improved articular cartilage formation and restored zonal structure.

    PubMed

    Lu, Chia-Hsin; Yeh, Tsung-Szu; Yeh, Chia-Lin; Fang, Yu-Hua Dean; Sung, Li-Yu; Lin, Shih-Yeh; Yen, Tzu-Chen; Chang, Yu-Han; Hu, Yu-Chen

    2014-01-01

    Adipose-derived stem cells (ASCs) hold promise for cartilage regeneration but their chondrogenesis potential is inferior. Here, we used a baculovirus (BV) system that exploited FLPo/Frt-mediated transgene recombination and episomal minicircle formation to genetically engineer rabbit ASCs (rASCs). The BV system conferred prolonged and robust TGF-β3/BMP-6 expression in rASCs cultured in porous scaffolds, which critically augmented rASCs chondrogenesis and suppressed osteogenesis/hypertrophy, leading to the formation of cartilaginous constructs with improved maturity and mechanical properties in 2-week culture. Twelve weeks after implantation into full-thickness articular cartilage defects in rabbits, these engineered constructs regenerated neocartilages that resembled native hyaline cartilages in cell morphology, matrix composition and mechanical properties. The neocartilages also displayed cartilage-specific zonal structures without signs of hypertrophy and degeneration, and eventually integrated with host cartilages. In contrast, rASCs that transiently expressed TGF-β3/BMP-6 underwent osteogenesis/hypertrophy and resulted in the formation of inferior cartilaginous constructs, which after implantation regenerated fibrocartilages. These data underscored the crucial role of TGF-β3/BMP-6 expression level and duration in rASCs in the cell differentiation, constructs properties and in vivo repair. The BV-engineered rASCs that persistently express TGF-β3/BMP-6 improved the chondrogenesis, in vitro cartilaginous constructs production and in vivo hyaline cartilage regeneration, thus representing a remarkable advance in cartilage engineering.

  19. 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

  20. Hypoxia Potentiates Anabolic Effects of Exogenous Hyaluronic Acid in Rat Articular Cartilage

    PubMed Central

    Ichimaru, Shohei; Nakagawa, Shuji; Arai, Yuji; Kishida, Tsunao; Shin-Ya, Masaharu; Honjo, Kuniaki; Tsuchida, Shinji; Inoue, Hiroaki; Fujiwara, Hiroyoshi; Shimomura, Seiji; Mazda, Osam; Kubo, Toshikazu

    2016-01-01

    Hyaluronic acid (HA) is used clinically to treat osteoarthritis (OA), but its pharmacological effects under hypoxic conditions remain unclear. Articular chondrocytes in patients with OA are exposed to a hypoxic environment. This study investigated whether hypoxia could potentiate the anabolic effects of exogenous HA in rat articular cartilage and whether these mechanisms involved HA receptors. HA under hypoxic conditions significantly enhanced the expression of extracellular matrix genes and proteins in explant culture, as shown by real-time reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, and dimethylmethylene blue (DMMB) assays. Staining with Safranin-O and immunohistochemical staining with antibody to type II collagen were also enhanced in pellet culture. The expression of CD44 was increased by hypoxia and significantly suppressed by transfection with siRNAs targeting hypoxia-inducible factor 1 alpha (siHIF-1α). These findings indicate that hypoxia potentiates the anabolic effects of exogenous HA by a mechanism in which HIF-1α positively regulates the expression of CD44, enhancing the binding affinity for exogenous HA. The anabolic effects of exogenous HA may increase as OA progresses. PMID:27347945

  1. Osteochondral autologous transplantation for the treatment of full-thickness articular cartilage defects of the shoulder.

    PubMed

    Scheibel, M; Bartl, C; Magosch, P; Lichtenberg, S; Habermeyer, P

    2004-09-01

    We performed eight osteochondral autologous transplantations from the knee joint to the shoulder. All patients (six men, two women; mean age 43.1 years) were documented prospectively. In each patient the stage of the osteochondral lesion was Outerbridge grade IV with a mean size of the affected area of 150 mm2. All patients were assessed by using the Constant score for the shoulder and the Lysholm score for the knee. Standard radiographs, magnetic resonance imaging and second-look arthroscopy were used to assess the presence of glenohumeral osteoarthritis and the integrity of the grafts. After a mean of 32.6 months (8 to 47), the mean Constant score increased significantly. Magnetic resonance imaging revealed good osseointegration of the osteochondral plugs and congruent articular cartilage at the transplantation site in all but one patient. Second-look arthroscopy performed in two cases revealed a macroscopically good integration of the autograft with an intact articular surface. Osteochondral autologous transplantation in the shoulder appears to offer good clinical results for treating full-thickness osteochondral lesions of the glenohumeral joint. However, our study suggests that the development of osteoarthritis and the progression of pre-existing osteoarthritic changes cannot be altered by this technique.

  2. Condensed cellular seeded collagen gel as an improved biomaterial for tissue engineering of articular cartilage.

    PubMed

    Mueller-Rath, Ralf; Gavénis, Karsten; Andereya, Stefan; Mumme, Torsten; Albrand, Monique; Stoffel, Marcus; Weichert, Dieter; Schneider, Ulrich

    2010-01-01

    Three-dimensional autologous chondrocyte implantation based on collagen gel as matrix scaffold has become a clinically applied treatment for focal defects of articular cartilage. However, the low biomechanical properties of collagen gel makes intraoperative handling difficult and creates the risk of early damages to the vulnerable implant. The aim of the study was to create a stabilized form of collagen gel and to evaluate its biomechanical and biochemical properties.Collagen type-I gel was seeded with human articular chondrocytes. 20 samples were subject to condensation which was achieved mechanically by compression and filtration. Control samples were left uncondensed. From both types of gels 10 samples were used for initial biomechanical evaluation by means of unconfined compression and 10 samples were cultivated under standard conditions in vitro. Following cultivation the samples were evaluated by conventional histology and immunohistochemistry. The proliferation rate was calculated and matrix gene expression was quantified by real-time PCR.The biomechanical tests revealed a higher force carrying capacity of the condensed specimens. Strain rate dependency and relaxation was seen in both types of collagen gel representing viscoelastic material properties. Cells embedded within the condensed collagen gel were able to produce extracellular matrix proteins and showed proliferation.Condensed collagen gel represents a mechanically improved type of biomaterial which is suitable for three-dimensional autologous chondrocyte implantation.

  3. Deformation of articular cartilage during static loading of a knee joint--experimental and finite element analysis.

    PubMed

    Halonen, K S; Mononen, M E; Jurvelin, J S; Töyräs, J; Salo, J; Korhonen, R K

    2014-07-18

    Novel conical beam CT-scanners offer high resolution imaging of knee structures with i.a. contrast media, even under weight bearing. With this new technology, we aimed to determine cartilage strains and meniscal movement in a human knee at 0, 1, 5, and 30 min of standing and compare them to the subject-specific 3D finite element (FE) model. The FE model of the volunteer׳s knee, based on the geometry obtained from magnetic resonance images, was created to simulate the creep. The effects of collagen fibril network stiffness, nonfibrillar matrix modulus, permeability and fluid flow boundary conditions on the creep response in cartilage were investigated. In the experiment, 80% of the maximum strain in cartilage developed immediately, after which the cartilage continued to deform slowly until the 30 min time point. Cartilage strains and meniscus movement obtained from the FE model matched adequately with the experimentally measured values. Reducing the fibril network stiffness increased the mean strains substantially, while the creep rate was primarily influenced by an increase in the nonfibrillar matrix modulus. Changing the initial permeability and preventing fluid flow through noncontacting surfaces had a negligible effect on cartilage strains. The present results improve understanding of the mechanisms controlling articular cartilage strains and meniscal movements in a knee joint under physiological static loading. Ultimately a validated model could be used as a noninvasive diagnostic tool to locate cartilage areas at risk for degeneration.

  4. Unique glycosignature for intervertebral disc and articular cartilage cells and tissues in immaturity and maturity

    PubMed Central

    Collin, E. C.; Kilcoyne, M.; White, S. J.; Grad, S.; Alini, M.; Joshi, L.; Pandit, A. S.

    2016-01-01

    In this study, on/off markers for intervertebral disc (IVD) and articular cartilage (AC) cells (chondrocytes) and distinct glycoprofiles of cell and tissue-types were identified from immaturity to maturity. Three and eleven month-old ovine IVD and AC tissues were histochemically profiled with a panel of lectins and antibodies. Relationships between tissue and cell types were analysed by hierarchical clustering. Chondroitin sulfate (CS) composition of annulus fibrosus (AF), nucleus pulposus (NP) and AC tissues was determined by HPLC analysis. Clear on/off cell type markers were identified, which enabled the discrimination of chondrocytes, AF and NP cells. AF and NP cells were distinguishable using MAA, SNA-I, SBA and WFA lectins, which bound to both NP cells and chondrocytes but not AF cells. Chondrocytes were distinguished from NP and AF cells with a specific binding of LTA and PNA lectins to chondrocytes. Each tissue showed a unique CS composition with a distinct switch in sulfation pattern in AF and NP tissues upon disc maturity while cartilage maintained the same sulfation pattern over time. In conclusion, distinct glycoprofiles for cell and tissue-types across age groups were identified in addition to altered CS composition and sulfation patterns for tissue types upon maturity. PMID:26965377

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

    PubMed Central

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

    2008-01-01

    Background Assessment of gene expression is an important component of osteoarthritis (OA) research, greatly improved by the development of quantitative real-time PCR (qPCR). This technique requires normalization for precise results, yet no suitable reference genes have been identified in human articular cartilage. We have examined ten well-known reference genes to determine the most adequate for this application. Results Analyses of expression stability in cartilage from 10 patients with hip OA, 8 patients with knee OA and 10 controls without OA were done with classical statistical tests and the software programs geNorm and NormFinder. Results from the three methods of analysis were broadly concordant. Some of the commonly used reference genes, GAPDH, ACTB and 18S RNA, performed poorly in our analysis. In contrast, the rarely used TBP, RPL13A and B2M genes were the best. It was necessary to use together several of these three genes to obtain the best results. The specific combination depended, to some extent, on the type of samples being compared. Conclusion Our results provide a satisfactory set of previously unused reference genes for qPCR in hip and knee OA This confirms the need to evaluate the suitability of reference genes in every tissue and experimental situation before starting the quantitative assessment of gene expression by qPCR. PMID:18226276

  6. A model to predict the permeation kinetics of dimethyl sulfoxide in articular cartilage.

    PubMed

    Yu, Xiaoyi; Chen, Guangming; Zhang, Shaozhi

    2013-02-01

    Cryopreservation of articular cartilage (AC) has excited great interest due to the practical surgical importance of this tissue. Characterization of permeation kinetics of cryoprotective agents (CPA) in AC is important for designing optimal CPA addition/removal protocols to achieve successful cryopreservation. Permeation is predominantly a mass diffusion process. Since the diffusivity is a function of temperature and concentration, analysis of the permeation problem would be greatly facilitated if a predictive method were available. This article describes, a model that was developed to predict the permeation kinetics of dimethyl sulfoxide (DMSO) in AC. The cartilage was assumed as a porous medium, and the effect(s) of composition and thermodynamic nonideality of the DMSO solution were considered in model development. The diffusion coefficient was correlated to the infinite dilution coefficients through a binary diffusion thermodynamic model. The UNIFAC model was used to evaluate the activity coefficient, the Vignes equation was employed to estimate the composition dependence of the diffusion coefficient, and the Siddiqi-Lucas correlation was applied to determine the diffusion coefficients at infinite dilution. Comparisons of the predicted overall DMSO uptake by AC with the experimental data over wide temperature and concentration ranges [1~37°C, 10~47% (w/w)] show that the model can accurately describe the permeation kinetics of DMSO in AC [coefficient of determination (R(2)): 0.961~0.996, mean relative error (MRE): 2.2~9.1%].

  7. MRI properties of a unique hypo-intense layer in degraded articular cartilage

    NASA Astrophysics Data System (ADS)

    Wang, Nian; Badar, Farid; Xia, Yang

    2015-11-01

    To investigate the characteristics of a hypo-intense laminar appearance in articular cartilage under external loading, microscopic magnetic resonance imaging (μMRI) T1, T2 and T1ρ experiments of a total of 15 specimens of healthy and trypsin-degraded cartilage were performed at different soaking solutions (saline and 100 mM phosphate buffered saline (PBS)). T2 and T1ρ images of the healthy tissue in saline showed no load-induced laminar appearance, while a hypo-intense layer was clearly visible in the deep part of the degraded tissue at the magic angle. A significant difference was found between T2 values at 0° and 55° (from 16.5  ±  2.8 ms to 20.2  ±  2.7 ms, p  =  0.0005), and at 0° and 90° (16.5  ±  2.8 ms to 21.3  ±  2.6 ms, p  <  0.0001) in saline solution. In contrast, this hypo-intense laminar appearance largely disappeared when tissue was soaked in PBS. The visualization of this hypo-intensity appearance in different soaking mediums calls for caution in interpreting the data of relaxation times, chemical exchange and collagen fiber deformation.

  8. Characterization of Collagen Type I and II Blended Hydrogels for Articular Cartilage Tissue Engineering.

    PubMed

    Vázquez-Portalatı N, Nelda; Kilmer, Claire E; Panitch, Alyssa; Liu, Julie C

    2016-10-10

    Biomaterials that provide signals present in the native extracellular matrix have been proposed as scaffolds to support improved cartilage regeneration. This study harnesses the biological activity of collagen type II and the superior mechanical properties of collagen type I by characterizing gels made of collagen type I and II blends. The collagen blend hydrogels were able to incorporate both types of collagen and retained chondroitin sulfate and hyaluronic acid. Cryo-scanning electron microscopy images showed that the 3:1 ratio of collagen type I to type II gels had a lower void space percentage (36.4%) than the 1:1 gels (46.5%). The complex modulus was larger for the 3:1 gels (G* = 5.0 Pa) compared to the 1:1 gels (G* = 1.2 Pa). The 3:1 blend consistently formed gels with superior mechanical properties compared to the other blends and has the potential to be implemented as a scaffold for articular cartilage engineering.

  9. Subregional Anatomical Distribution of T2 Values of Articular Cartilage in Asymptomatic Hips

    PubMed Central

    Surowiec, Rachel K.; Ferro, Fernando P.; Lucas, Erin P.; Saroki, Adriana J.; Dornan, Grant J.; Fitzcharles, Eric K.; Anz, Adam W.; Smith, W. Sean; Wilson, Katharine J.; Philippon, Marc J.

    2014-01-01

    Objective: A standardized definition of normative T2 values across the articular surface of the hip must be defined in order to fully understand T2 values for detecting early degeneration. Therefore, in this article, we seek to lay foundational methodology for reproducible quantitative evaluation of hip cartilage damage using T2 mapping to determine the normative T2 values in asymptomatic individuals. Design: Nineteen prospectively enrolled asymptomatic volunteers (age 18-35 years, males 10, females 9, alpha angle 49.3º ± 7.2º) were evaluated with a sagittal T2 mapping sequence at 3.0 T magnetic resonance imaging. Acetabular and femoral cartilage was manually segmented directly on the second echo of the T2 mapping sequence by 3 raters, twice. Segmentations were divided into 12 subregions modified from the geographic zone method. Median T2 values within each subregion were compiled for further analysis and interrater and intrarater reliability was assessed. Results: In the femur, the posterior-superior subregion was significantly higher (P ≤ 0.05) than those in the posterior-inferior and anterior-inferior subregions. In the acetabulum, the anterior-inferior subregion was significantly higher (P ≤ 0.001) than in the anterior-superior, middle, and posterior-inferior subregions. T2 values of the posterior-superior subregion were significantly higher (P ≤ 0.05) than the anterior-superior, middle, and posterior-inferior subregions. Interrater agreement was generally fair to good. PMID:26069695

  10. Radiofrequency energy-induced heating of bovine articular cartilage using a bipolar radiofrequency electrode.

    PubMed

    Shellock, F G; Shields, C L

    2000-01-01

    Radiofrequency energy is used for thermal-assisted chondroplasty to treat grade II and III chondromalacia with the lowest possible energy setting that achieves the desired result. The purpose of this in vitro study was to determine the temperature changes associated with the use of radiofrequency energy delivered at different settings to bovine articular cartilage using a bipolar electrode. Cartilage samples were placed in a temperature-controlled (37 degrees C) saline bath for the delivery of radiofrequency energy. A fluoroptic thermometry probe was positioned to record the temperatures at the electrode-tissue interface. The electrode was activated for 2 seconds at settings of V2-120, V2-60, V2-40, and V2-20 in two modes: ablation and desiccation. Additionally, the cartilage samples were visually inspected to determine changes in appearance. The highest average temperatures were as follows: ablation mode, 78.5 degrees C (V2-120), 62.6 degrees C (V2-60), 58.1 degrees C (V2-40), and 54.1 degrees C (V2-20); desiccation mode, 71.8 degrees C (V2-120), 61.4 degrees C (V2-60), 57.7 degrees C (V2-40), and 53.3 degrees C (V2-20). There were statistically significant increases in temperatures associated with each of the respective settings. There were no substantial visual changes produced by the V2-20 settings, while the other settings produced a gradation of effects. These data provide information to help guide the use of a bipolar radiofrequency electrode and electrosurgical system for thermal-assisted chondroplasty.

  11. Quantitative assessment of articular cartilage with morphologic, acoustic and mechanical properties obtained using high-frequency ultrasound.

    PubMed

    Wang, Shu-Zhe; Huang, Yan-Ping; Saarakkala, Simo; Zheng, Yong-Ping

    2010-03-01

    Osteoarthritis (OA) is one of the most common joint diseases among adults, and its early detection is still not possible. In this study, high-frequency ultrasound and ultrasound-assisted mechanical testing systems were used to quantitatively measure the morphologic, acoustic and mechanical properties of normal and enzymatically degraded bovine articular cartilages in vitro. A total of 40 osteochondral cartilage plugs were prepared from 20 bovine patellae (n=20x2) and divided into two groups for collagenase and trypsin digestions, respectively. A high-frequency ultrasound system (center frequency: 40 MHz) was used to analyze the surface integrity (ultrasound roughness index, URI), thickness and acoustic properties of the articular cartilages before and after enzymatic degradations. Acoustic parameters included the integrated reflection coefficient (IRC) from the cartilage surface, reflection from the cartilage-bone interface (AIB(bone)), integrated attenuation (IA) and integrated backscatter (IBS) of the internal cartilage tissue. A newly developed ultrasound water jet indentation system was used to assess the mechanical properties of the cartilage samples. The results showed that the URI increased significantly (p<0.05) after collagenase digestion while no significant change (p>0.05) was found after trypsin digestion. With regard to acoustic parameters, the IRC decreased significantly (p<0.05) after collagenase digestion while no significant change (p>0.05) was found after trypsin digestion. The AIB(bone) demonstrated an insignificant change after collagenase digestion (p>0.05) but a significant decrease after trypsin digestion (p<0.05). Both enzymatic degradation groups showed insignificant differences (p>0.05) in the IA but a significant increase (p<0.05) in the IBS after both enzymatic degradations. The apparent stiffness measured by ultrasound water jet indentation suggested that articular cartilage from both groups became significantly softer (p<0.05) after

  12. 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).

  13. Wnt7a Inhibits IL-1β Induced Catabolic Gene Expression and Prevents Articular Cartilage Damage in Experimental Osteoarthritis

    PubMed Central

    Gibson, Averi L.; Hui Mingalone, Carrie K.; Foote, Andrea T.; Uchimura, Tomoya; Zhang, Ming; Zeng, Li

    2017-01-01

    Wnt7a is a protein that plays a critical role in skeletal development. However, its effect on cartilage homeostasis under pathological conditions is not known. In this study, we found a unique inverse correlation between Wnt7a gene expression and that of MMP and IL-1β in individual human OA cartilage specimens. Upon ectopic expression in primary human articular chondrocytes, Wnt7a inhibited IL-1β-induced MMP and iNOS gene expression. Western blot analysis indicated that Wnt7a induced both canonical Wnt signaling and NFAT and Akt non-canonical signaling. Interestingly, inhibiting the canonical and Akt pathway did not affect Wnt7a activity. However, inhibiting the NFAT pathway impaired Wnt7a’s ability to inhibit MMP expression, suggesting that Wnt7a requires NFAT signaling to exert this function. In vivo, intraarticular injection of lentiviral Wnt7a strongly attenuated articular cartilage damage induced by destabilization of the medial meniscus (DMM) OA-inducing surgery in mice. Consistently, Wnt7a also inhibited the progressive increase of joint MMP activity in DMM animals. These results indicate that Wnt7a signaling inhibits inflammatory stimuli-induced catabolic gene expression in human articular chondrocytes and is sufficient to attenuate MMP activities and promote joint cartilage integrity in mouse experimental OA, demonstrating a novel effect of Wnt7a on regulating OA pathogenesis. PMID:28165497

  14. Real-time electro-mechano-acoustic imaging for monitoring interactions between trypsin and different inhibitors in articular cartilage.

    PubMed

    Zheng, Yong-Ping; Wang, Qing; Butt, Yoki Kwok Chu

    2011-03-01

    The purpose of this study was to observe the real-time interactions between trypsin and various inhibitors in articular cartilage in vitro using a novel electro-mechano-acoustic imaging method. Monitored in real-time, articular cartilage specimens from bovine patellae were first treated with trypsin to reach half proteoglycan depletion (Phase I), then the trypsin solution was replaced with (i) physiological saline buffer (PS), (ii) fetal bovine serum (FBS), (iii) protease inhibitor cocktail (PI) and (iv) 10% formalin (F), respectively, to observe their effects on residual digestion (Phase II). Ultrasound radio frequency signals from the articular cartilage were used to form a M-mode image, where the interface between trypsin digested and intact cartilage tissues could be observed with an additional echo generated. The inhibition time, the digestion depth and digestion fraction were measured for each specimen. The results showed that the dilution of trypsin using saline solution was not sufficient to stop the enzyme action instantly. Although groups FBS and PI had a similar inhibition time of approximately 1.5 h, their digestion depth was obviously different (0.25±0.03 and 0.06±0.06 mm, respectively). In contrast, formalin only took <30 min to stop the trypsin digestion with almost no further digestion. The results demonstrated that the current system was capable of monitoring the trypsin digestion and inhibition process in real time. Also, different chemicals affected the residual trypsin digestion to different degrees.

  15. Proteoglycan concentrations in healthy and diseased articular cartilage by Fourier transform infrared imaging and principal component regression

    NASA Astrophysics Data System (ADS)

    Yin, Jianhua; Xia, Yang

    2014-12-01

    Fourier transform infrared imaging (FTIRI) combining with principal component regression (PCR) analysis were used to determine the reduction of proteoglycan (PG) in articular cartilage after the transection of the anterior cruciate ligament (ACL). A number of canine knee cartilage sections were harvested from the meniscus-covered and meniscus-uncovered medial tibial locations from the control joints, the ACL joints at three time points after the surgery, and their contralateral joints. The PG loss in the ACL cartilage was related positively to the durations after the surgery. The PG loss in the contralateral knees was less than that of the ACL knees. The PG loss in the meniscus-covered cartilage was less than that of the meniscus-uncovered tissue in both ACL and contralateral knees. The quantitative mapping of PG loss could monitor the disease progression and repair processes in arthritis.

  16. Proteoglycan Concentrations in Healthy and Diseased Articular Cartilage by Fourier Transform Infrared Imaging and Principal Component Regression

    PubMed Central

    Yin, Jianhua; Xia, Yang

    2014-01-01

    Fourier transform infrared imaging (FTIRI) combining with principal component regression (PCR) analysis were used to determine the reduction of proteoglycan (PG) in articular cartilage after the transection of the anterior cruciate ligament (ACL). A number of canine knee cartilage sections were harvested from the meniscus-covered and meniscus-uncovered medial tibial locations from the control joints, the ACL joints at three time points after the surgery, and their contralateral joints. The PG loss in the ACL cartilage was related positively to the durations after the surgery. The PG loss in the contralateral knees was less than that of the ACL knees. The PG loss in the meniscus-covered cartilage was less than that of the meniscus-uncovered tissue in both ACL and contralateral knees. The quantitative mapping of PG loss could monitor the disease progression and repair processes in arthritis. PMID:25000570

  17. The collagen structure of equine articular cartilage characterized using polarization-sensitive optical coherence tomography and non-linear microscopy

    NASA Astrophysics Data System (ADS)

    Mansfield, Jessica C.; Ugryumova, Nadya; Knapp, Karen M.; Matcher, Stephen J.

    2006-09-01

    Equine articular cartilage has been imaged using both polarization-sensitive optical coherence tomography (PS-OCT) and non-linear microscopy. PS-OCT has been used to spatially map the birefringence in the cartilage and we have found that in the vicinity of the lesion the images display a characteristic disruption in the regular birefringence bands shown by normal cartilage. We also note that significant (e.g. x2) variations in the apparent birefringence of samples taken from young (18 month) animals that otherwise appear visually homogeneous are found over spatial scales of a few millimeters. We have also imaged the cartilage using non-linear microscopy and compare the scans taken with second harmonic generation (SHG) light and the two photon fluorescence (TPF) light. SHG images collected using 800 nm excitation reveals the spatial distribution of collagen fibers, whilst TPF images clearly shows the distribution of intracellular and pericellular fluorophores.

  18. 24R,25-Dihydroxyvitamin D3 Protects against Articular Cartilage Damage following Anterior Cruciate Ligament Transection in Male Rats

    PubMed Central

    Boyan, Barbara D.; Hyzy, Sharon L.; Pan, Qingfen; Scott, Kayla M.; Coutts, Richard D.; Healey, Robert; Schwartz, Zvi

    2016-01-01

    Osteoarthritis (OA) in humans is associated with low circulating 25-hydroxyvitamin D3 [25(OH)D3]. In vitamin D replete rats, radiolabeled 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3] accumulates in articular cartilage following injection of [3H]-25(OH)D3. Previously, we showed that 24R,25(OH)2D3 blocks chondrocyte apoptosis via phospholipase D and p53, suggesting a role for 24R,25(OH)2D3 in maintaining cartilage health. We examined the ability of 24R,25(OH)2D3 to prevent degenerative changes in articular cartilage in an OA-like environment and the potential mechanisms involved. In vitro, rat articular chondrocytes were treated with IL-1β with and without 24R,25(OH)2D3 or 1α,25(OH)2D3. 24R,25(OH)2D3 but not 1α,25(OH)2D3 blocked the effects of IL-1β in a dose-dependent manner, and its effect was partially mediated through the TGF-β1 signaling pathway. In vivo, unilateral anterior cruciate ligament transections were performed in immunocompetent rats followed by intra-articular injections of 24R,25(OH)2D3 or vehicle (t = 0, 7, 14, 21 days). Tissues were harvested on day 28. Joints treated with vehicle had changes typical of OA whereas joints treated with 24R,25(OH)2D3 had less articular cartilage damage and levels of inflammatory mediators. These results indicate that 24R,25(OH)2D3 protects against OA, and suggest that it may be a therapeutic approach for preventing trauma-induced osteoarthritis. PMID:27575371

  19. Ultrastructural immunolocalization of cartilage oligomeric matrix protein (COMP) in the articular cartilage on the equine third carpal bone in trained and untrained horses.

    PubMed

    Skiöldebrand, E; Ekman, S; Heinegård, D; Hultenby, K

    2010-04-01

    The present study was designed to delineate the presence of COMP at the ultrastructural level comparing concentrations between two areas of articular cartilage from the equine third carpal bone, subjected to different loading, from trained and untrained horses. We also analyzed the fibril thickness of collagen type II in the same compartments and zones. Samples were collected from high load-bearing areas of the dorsal radial facet (intermittent high load) and an area of the palmar condyle (low constant load) in five non-trained and three trained young racehorses. The data show that COMP is much less abundant in the matrix in intermittent high loaded areas of articular cartilage from trained horses as compared to the untrained horses (p=0.036). On the other hand, the untrained horses often displayed a higher immunolabeling in loaded areas compared to unloaded areas, indicating that an adequate dynamic load promotes COMP synthesis and/or retention, while an excessive load may have an opposite effect. The collagen fibril diameter showed marked variation between individuals. The present study indicates that dynamic in vivo compression at high load and frequency lowers matrix content of COMP in the articular cartilage of the third carpal bone. It also indicates that the collagen network is influenced by mechanical load following by strenuous exercise.

  20. Fibril reinforced poroelastic model predicts specifically mechanical behavior of normal, proteoglycan depleted and collagen degraded articular cartilage.

    PubMed

    Korhonen, Rami K; Laasanen, Mikko S; Töyräs, Juha; Lappalainen, Reijo; Helminen, Heikki J; Jurvelin, Jukka S

    2003-09-01

    Degradation of collagen network and proteoglycan (PG) macromolecules are signs of articular cartilage degeneration. These changes impair cartilage mechanical function. Effects of collagen degradation and PG depletion on the time-dependent mechanical behavior of cartilage are different. In this study, numerical analyses, which take the compression-tension nonlinearity of the tissue into account, were carried out using a fibril reinforced poroelastic finite element model. The study aimed at improving our understanding of the stress-relaxation behavior of normal and degenerated cartilage in unconfined compression. PG and collagen degradations were simulated by decreasing the Young's modulus of the drained porous (nonfibrillar) matrix and the fibril network, respectively. Numerical analyses were compared to results from experimental tests with chondroitinase ABC (PG depletion) or collagenase (collagen degradation) digested samples. Fibril reinforced poroelastic model predicted the experimental behavior of cartilage after chondroitinase ABC digestion by a major decrease of the drained porous matrix modulus (-64+/-28%) and a minor decrease of the fibril network modulus (-11+/-9%). After collagenase digestion, in contrast, the numerical analyses predicted the experimental behavior of cartilage by a major decrease of the fibril network modulus (-69+/-5%) and a decrease of the drained porous matrix modulus (-44+/-18%). The reduction of the drained porous matrix modulus after collagenase digestion was consistent with the microscopically observed secondary PG loss from the tissue. The present results indicate that the fibril reinforced poroelastic model is able to predict specifically characteristic alterations in the stress-relaxation behavior of cartilage after enzymatic modifications of the tissue. We conclude that the compression-tension nonlinearity of the tissue is needed to capture realistically the mechanical behavior of normal and degenerated articular cartilage.

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

    NASA Astrophysics Data System (ADS)

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

    2009-03-01

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

  2. Elevated tibiofemoral articular contact stress predicts risk for bone marrow lesions and cartilage damage at 30 months

    PubMed Central

    Segal, NA; Kern, A; Anderson, DD; Niu, J; Lynch, J; Guermazi, A; Torner, JC; Brown, TD; Nevitt, M

    2012-01-01

    Objective As cartilage loss and bone marrow lesions (BMLs) are associated with knee joint pain and structural worsening, this study assessed whether non-invasive estimates of articular contact stress may longitudinally predict risk for worsening of knee cartilage morphology and BMLs. Design This was a longitudinal cohort study of adults aged 50-79 years with risk factors for knee osteoarthritis. Baseline and follow-up measures included WORMS classification of knee cartilage morphology and BMLs. Tibiofemoral geometry was manually segmented on baseline MRI, and 3D tibiofemoral point clouds were registered into subject-specific loaded apposition using fixed-flexion knee radiographs. Discrete element analysis (DEA) was used to estimate mean and peak contact stresses for the medial and lateral compartments. The association of baseline contact stress with worsening cartilage and BMLs in the same sub-region over 30 months was assessed using conditional logistic regression. Results Subjects (N=38, 60.5% female) had a mean±SD age and BMI of 63.5±8.4 years and 30.5±3.7 kg/m2 respectively. Elevated mean articular contact stress at baseline was associated with worsening cartilage morphology and worsening BMLs by 30-months, with OR (95%CI) of 4.0 (2.5, 6.4) and 6.6 (2.7, 16.5) respectively. Peak contact stress also was significantly associated with worsening cartilage morphology and BMLs {1.9 (1.5, 2.3) and 2.3 (1.5, 3.6)}(all p<0.0001). Conclusions Detection of higher contact stress 30 months prior to structural worsening suggests an etiological role for mechanical loading. Estimation of articular contact stress with DEA is an efficient and accurate means of predicting sub-region-specific knee joint worsening and may be useful in guiding prognosis and treatment. PMID:22698440

  3. Expression of transforming growth factor-beta 1 in normal and dyschondroplastic articular growth cartilage of the young horse.

    PubMed

    Henson, F M; Schofield, P N; Jeffcott, L B

    1997-11-01

    This study describes the distribution pattern of transforming growth factor-beta 1 (TGF-beta 1) mRNA and protein in normal pre- and post natal growth cartilage and alterations present in lesions of dyschondroplasia (osteochondrosis). TGF-beta 1 expression and immunoreactivity have been investigated by in situ hybridisation and immunolocalisation in the articular/epiphyseal growth cartilage of the lateral trochlear ridge of the distal femur. Cartilage was obtained from 19 normal Thoroughbred horses (5 prenatal and 14 post natal horses) and 15 post natal horses with dyschondroplasia (DCP). TGF-beta 1 mRNA expression and immunoreactivity were detected in the proliferative and upper hypertrophic zones in both pre- and post natal normal articular/epiphyseal cartilage. However, mRNA itself was only detected in the mid- and lower hypertrophic zones. Immunoreactivity was identified intracellularly with some nuclear staining observed. In focal lesions of DCP mRNA expression and immunoreactivity were reduced compared to normal cartilage, but strong mRNA expression was observed in the chondrocyte clusters immediately surrounding a lesion of DCP. The results described in this study demonstrate alterations in TGF-beta 1 dyschondroplastic lesions and indicate that it could be involved in the pathogenesis of this condition in the horse.

  4. Intra-articular injection of synovial mesenchymal stem cells improves cartilage repair in a mouse injury model

    PubMed Central

    Mak, J.; Jablonski, C. L.; Leonard, C. A.; Dunn, J. F.; Raharjo, E.; Matyas, J. R.; Biernaskie, J.; Krawetz, R. J.

    2016-01-01

    Controversy remains whether articular cartilage has an endogenous stem/progenitor cell population, since its poor healing capacity after injury can lead to diseases such as osteoarthritis. In the joint environment there are mesenchymal stem/progenitor cells (MSCs) in the synovial membrane and synovial fluid that can differentiate into cartilage, but it is still under debate if these cells contribute to cartilage repair in vivo. In this study, we isolated a Sca-1 positive, chondrogenesis capable population of mouse synovial MSCs from C57BL6 and MRL/MpJ “super-healer” strains. Intra-articular injection of Sca-1 + GFP + synovial cells from C57BL6 or MRL/MpJ into C57BL6 mice following cartilage injury led to increased cartilage repair by 4 weeks after injury. GFP expression was detected in the injury site at 2 weeks, but not 4 weeks after injury. These results suggest that synovial stem/progenitor cells, regardless of strain background, have beneficial effects when injected into an injured joint. MSCs derived from MRL/MpJ mice did not promote an increased repair capacity compared to MSCs derived from non-healing C57BL6 controls; however, MRL/MpJ MSCs were observed within the defect area at the time points examined, while C57BL6 MSCs were not. PMID:26983696

  5. Intact pericellular matrix of articular cartilage is required for unactivated discoidin domain receptor 2 in the mouse model.

    PubMed

    Xu, Lin; Polur, Ilona; Servais, Jacqueline M; Hsieh, Sirena; Lee, Peter L; Goldring, Mary B; Li, Yefu

    2011-09-01

    Increased expression of the discoidin domain receptor 2 (DDR2) results from its interaction with collagen type II. This induces expression of matrix metalloproteinase (MMP)-13, leading to osteoarthritis (OA). To investigate the impact of the pericellular matrix of chondrocytes on DDR2, we generated a mouse model with inducible overexpression of DDR2 in cartilage. Conditional overexpression of DDR2 in mature mouse articular cartilage was controlled via the cartilage oligomeric matrix protein promoter using the Tet-Off-inducible system. Doxycycline was withdrawn at 1 month of age, and knee joints were examined at 2, 3, and 4 months of age. Microsurgery was performed on 3-month-old transgenic mice overexpressing DDR2 to destabilize the medial meniscus, and serial paraffin sections were examined at 2, 4, 8, and 12 weeks after surgery. DDR2 expression increased in the knee joints of transgenic mice. However, the increased DDR2 did not induce MMP-13 expression. No OA-like changes were observed in the transgenic mice at the age of 4 months. When transgenic mice were subjected to destabilizing of the medial meniscus, we observed accelerated progression to OA, which was associated with DDR2 activation. Therefore, conditionally overexpressing DDR2 in the mature articular cartilage of mouse knee joints requires activation to induce OA, and altered biomechanical stress can accelerate the onset of cartilage loss and progression to OA in transgenic mice.

  6. Intra-articular injection of synovial mesenchymal stem cells improves cartilage repair in a mouse injury model.

    PubMed

    Mak, J; Jablonski, C L; Leonard, C A; Dunn, J F; Raharjo, E; Matyas, J R; Biernaskie, J; Krawetz, R J

    2016-03-17

    Controversy remains whether articular cartilage has an endogenous stem/progenitor cell population, since its poor healing capacity after injury can lead to diseases such as osteoarthritis. In the joint environment there are mesenchymal stem/progenitor cells (MSCs) in the synovial membrane and synovial fluid that can differentiate into cartilage, but it is still under debate if these cells contribute to cartilage repair in vivo. In this study, we isolated a Sca-1 positive, chondrogenesis capable population of mouse synovial MSCs from C57BL6 and MRL/MpJ "super-healer" strains. Intra-articular injection of Sca-1 + GFP + synovial cells from C57BL6 or MRL/MpJ into C57BL6 mice following cartilage injury led to increased cartilage repair by 4 weeks after injury. GFP expression was detected in the injury site at 2 weeks, but not 4 weeks after injury. These results suggest that synovial stem/progenitor cells, regardless of strain background, have beneficial effects when injected into an injured joint. MSCs derived from MRL/MpJ mice did not promote an increased repair capacity compared to MSCs derived from non-healing C57BL6 controls; however, MRL/MpJ MSCs were observed within the defect area at the time points examined, while C57BL6 MSCs were not.

  7. Management of focal cartilage defects in the knee - Is ACI the answer?

    PubMed

    Strauss, Eric J; Fonseca, Lauren E; Shah, Mehul R; Yorum, Thomas

    2011-01-01

    Injuries to the articular cartilage of the knee are common. They alter the normal distribution of weightbearing forces and predispose patients to the development of degenerative joint disease. The management of focal chondral lesions continues to be problematic for the treating orthopaedic surgeon. Although many treatment options are currently available, none fulfill the criteria for an ideal repair solution: a hyaline repair tissue that completely fills the defect and integrates well with the surrounding normal cartilage. Autologous chondrocyte implantation (ACI) is a relatively new cell-based treatment method for full-thickness cartilage injuries that in recent years has increased in popularity, with early studies showing promising results. The current article reviews the nature of cartilage lesions in the knee and the treatment modalities utilized in their management, focusing on the role ACI plays in the surgical treatment of these complex injuries.

  8. Perlecan displays variable spatial and temporal immunolocalisation patterns in the articular and growth plate cartilages of the ovine stifle joint.

    PubMed

    Melrose, James; Smith, Susan; Cake, Martin; Read, Richard; Whitelock, John

    2005-06-01

    Perlecan is a modular heparan sulphate and/or chondroitin sulphate substituted proteoglycan of basement membrane, vascular tissues and cartilage. Perlecan acts as a low affinity co-receptor for fibroblast growth factors 1, 2, 7, 9, binds connective tissue growth factor and co-ordinates chondrogenesis, endochondral ossification and vascular remodelling during skeletal development; however, relatively little is known of its distribution in these tissues during ageing and development. The aim of the present study was to immunolocalise perlecan in the articular and epiphyseal growth plate cartilages of stifle joints in 2-day to 8-year-old pedigree merino sheep. Perlecan was prominent pericellularly in the stifle joint cartilages at all age points and also present in the inter-territorial matrix of the newborn to 19-month-old cartilage specimens. Aggrecan was part pericellular, but predominantly an extracellular proteoglycan. Perlecan was a prominent component of the long bone growth plates and displayed a pericellular as well as a strong ECM distribution pattern; this may indicate a so far unrecognised role for perlecan in the mineralisation of hypertrophic cartilage. A significant age dependant decline in cell number and perlecan levels was evident in the hyaline and growth plate cartilages. The prominent pericellular distribution of perlecan observed indicates potential roles in cell-matrix communication in cartilage, consistent with growth factor signalling, cellular proliferation and tissue development.

  9. Refraction-Contrast Articular Cartilage Image: Comparison of Depiction Abilities between In-Line Holographic Method and a Laue Type Analyzer Method

    NASA Astrophysics Data System (ADS)

    Shimao, Daisuke; Mori, Koichi; Sugiyama, Hiroshi; Hyodo, Kazuyuki

    2005-01-01

    Two kinds of refraction-contrast image, one obtained using the in-line holographic method and the other obtained using an analyzer crystal in the Laue geometry, from a specimen of a human articular cartilage were investigated using synchrotron X-rays at 30 keV. The former image was superior in spatial resolution and the latter image was superior in contrast regarding the delineation of the articular cartilage, which is invisible by the absorption contrast.

  10. Tantalum oxide nanoparticles for the imaging of articular cartilage using X-ray computed tomography: visualization of ex vivo/in vivo murine tibia and ex vivo human index finger cartilage.

    PubMed

    Freedman, Jonathan D; Lusic, Hrvoje; Snyder, Brian D; Grinstaff, Mark W

    2014-08-04

    The synthesis and characterization of tantalum oxide (Ta2O5) nanoparticles (NPs) as new X-ray contrast media for microcomputed tomography (μCT) imaging of articular cartilage are reported. NPs, approximately 5-10 nm in size, and possessing distinct surface charges, were synthesized using phosphonate (neutral), ammonium (cationic), and carboxylate (anionic) ligands as end functional groups. Assessment of a cartilage defect in a human cadaver distal metacarpophalangeal (MCP) joint with the ammonium nanoparticles showed good visualization of damage and preferential uptake in areas surrounding the defect. Finally, an optimized nontoxic cationic NP contrast agent was evaluated in an in vivo murine model and the cartilage was imaged. These nanoparticles represent a new type of contrast agent for imaging articular cartilage, and the results demonstrate the importance of surface charge in the design of nanoparticulate agents for targeting the surface or interior zones of articular cartilage.

  11. Melanocortin 1 Receptor-Signaling Deficiency Results in an Articular Cartilage Phenotype and Accelerates Pathogenesis of Surgically Induced Murine Osteoarthritis

    PubMed Central

    Hackmayer, Gerit; Greth, Carina; Bauer, Richard J.; Kleinschmidt, Kerstin; Bettenworth, Dominik; Böhm, Markus; Grifka, Joachim; Grässel, Susanne

    2014-01-01

    Proopiomelanocortin-derived peptides exert pleiotropic effects via binding to melanocortin receptors (MCR). MCR-subtypes have been detected in cartilage and bone and mediate an increasing number of effects in diathrodial joints. This study aims to determine the role of MC1-receptors (MC1) in joint physiology and pathogenesis of osteoarthritis (OA) using MC1-signaling deficient mice (Mc1re/e). OA was surgically induced in Mc1re/e and wild-type (WT) mice by transection of the medial meniscotibial ligament. Histomorphometry of Safranin O stained articular cartilage was performed with non-operated controls (11 weeks and 6 months) and 4/8 weeks past surgery. µCT–analysis for assessing epiphyseal bone architecture was performed as a longitudinal study at 4/8 weeks after OA-induction. Collagen II, ICAM-1 and MC1 expression was analysed by immunohistochemistry. Mc1re/e mice display less Safranin O and collagen II stained articular cartilage area compared to WT prior to OA-induction without signs of spontaneous cartilage surface erosion. This MC1-signaling deficiency related cartilage phenotype persisted in 6 month animals. At 4/8 weeks after OA-induction cartilage erosions were increased in Mc1re/e knees paralleled by weaker collagen II staining. Prior to OA-induction, Mc1re/e mice do not differ from WT with respect to bone parameters. During OA, Mc1re/e mice developed more osteophytes and had higher epiphyseal bone density and mass. Trabecular thickness was increased while concomitantly trabecular separation was decreased in Mc1re/e mice. Numbers of ICAM-positive chondrocytes were equal in non-operated 11 weeks Mc1re/e and WT whereas number of positive chondrocytes decreased during OA-progression. Unchallenged Mc1re/e mice display smaller articular cartilage covered area without OA-related surface erosions indicating that MC1-signaling is critical for proper cartilage matrix integrity and formation. When challenged with OA, Mc1re/e mice develop a more severe OA

  12. Morphological Study: Ultrastructural Aspects of Articular Cartilage and Subchondral Bone in Patients Affected by Post-Traumatic Shoulder Instability.

    PubMed

    Baudi, Paolo; Catani, Fabio; Rebuzzi, Manuela; Ferretti, Marzia; Smargiassi, Alberto; Campochiaro, Gabriele; Serafini, Fabio; Palumbo, Carla

    2016-12-16

    Post-traumatic shoulder instability is a frequent condition in active population, representing one of most disabling pathologies, due to altered balance involving joints. No data are so far available on early ultrastructural osteo-chondral damages, associated with the onset of invalidating pathologies, like osteoarthritis-OA. Biopsies of glenoid articular cartilage and sub-chondral bone were taken from 10 adult patients underwent arthroscopic stabilization. Observations were performed under Transmission Electron Microscopy-TEM in tangential, arcuate and radial layers of the articular cartilage and in the sub-chondral bone. In tangential and arcuate layers chondrocytes display normal and very well preserved ultrastructure, probably due to the synovial liquid supply; otherwise, throughout the radial layer (un-calcified and calcified) chondrocytes show various degrees of degeneration; occasionally, in the radial layer evidences of apoptosis/autophagy were also observed. Concerning sub-chondral bone, osteocytes next to the calcified cartilage also show signs of degeneration, while osteocytes farther from the osteo-chondral border display normal ultrastructure, probably due to the bone vascular supply. The ultrastructural features of the osteo-chondral complex are not age-dependent. This study represents the first complete ultrastructural investigation of the articular osteo-chondral complex in shoulder instability, evaluating the state of preservation/viability of both chondrocytes and osteocytes throughout the successive layers of articular cartilage and sub-chondral bone. Preliminary observations here collected represent the morphological basis for further deepening of pathogenesis related to shoulder instability, enhancing the relationship between cell shape and microenvironment; in particular, they could be useful in understanding if the early surgical treatment in shoulder instability could avoid the onset of OA. Anat Rec, 300:12-15, 2017. © 2016 Wiley

  13. Mesenchymal stem cells downregulate articular chondrocyte differentiation in noncontact coculture systems: implications in cartilage tissue regeneration.

    PubMed

    Xu, Lei; Wang, Qi; Xu, Feiyue; Ye, Zhaoyang; Zhou, Yan; Tan, Wen-Song

    2013-06-01

    While chondrogenesis of mesenchymal stem cells (MSCs) in vitro has been extensively studied, their participation in cartilage tissue repair remains unresolved. This study was designed to elucidate if MSCs affect the phenotype of articular chondrocytes (ACs). A combination of noncontact coculture modes was developed. Human or rabbit MSCs and rabbit ACs (rACs) were encapsulated in alginate hydrogel beads [three-dimensional (3D)] or cultured in a monolayer [two-dimensional (2D)] and subsequently cocultured in the Transwell(®) system. After coculture, cell morphology, growth, deposition of the cartilaginous extracellular matrix (ECM), and gene expression of rACs were investigated. It was found that upon coculture without a cell-cell contact, both 2D and 3D cultured MSCs dramatically induced the morphological transformation of 2D cultured rACs from round to a spindle-like shape, and however inhibited the generation of cellular aggregates of 3D cultured rACs. Most strikingly, a coculture resulted in a significantly less deposition of the cartilaginous ECM, including glycosaminoglycans and collagen type II by both 2D and 3D cultured rACs. Importantly, similar observations were achieved for rACs cultured in an MSC-conditioned medium, confirming the definite paracrine interactions between MSCs and rACs. Based on the analysis of gene expression, this phenotypic change of rACs was not identical as the dedifferentiation. To the best of our knowledge, this is a first study demonstrating that MSCs could downregulate chondrocytic differentiation of ACs and warrants considerations in cartilage tissue repair.

  14. Deboning broiler chicken legs and wings by dislocation of articular cartilage followed by stripping periosteum.

    PubMed

    Nakano, T; Ozimek, L; Betti, M

    2012-11-01

    The yield of deboned meat is an important economic factor affecting the profit of the meat industry. This study was undertaken to determine whether the yield of boneless meat from broiler chicken leg (thigh and drumstick) and wing (drumette and winglet) is improved by introducing a new deboning method consisting of articular cartilage dislocation followed by stripping periosteum. A total of 44 broiler chicken carcasses were used in the deboning experiment. Right and left legs or wings from the first 22 carcasses were assigned to the new and ordinary hand deboning methods, respectively. For the remaining 22 carcasses, right and left legs or wings were assigned to the ordinary and new methods, respectively. The weight of residue, composed of bone and small amounts of cartilage and noncartilaginous tissues obtained after deboning, was then compared between the right and left legs or wings to see the difference between the 2 methods. The removal of tibia, fibula, humerus, radius, or ulna resulted in formation of a hollow in boneless meat obtained. There was no difference (P > 0.05) between the right and left legs or wings in the weight of residue obtained after deboning as expected. The weight of residue was less (P < 0.05) with the new method compared with the ordinary method in all chicken parts examined. The difference of residue weight between the 2 methods accounted for 10, 12, 14, and 21% of the weight of residue obtained by the ordinary method in thigh, drumstick, drumette, and winglet, respectively. The new method may be useful to deboners at home kitchens as well as the poultry meat industry. The present study also showed the development of a secondary ossification center at the proximal end of the carpometacarpus of chickens. This is, to our knowledge, the first report of development of secondary ossification center in chicken wings.

  15. Monitoring the Progression of Spontaneous Articular Cartilage Healing with Infrared Spectroscopy

    PubMed Central

    O’Brien, Megan P.; Penmatsa, Madhuri; Palukuru, Uday; West, Paul; Yang, Xu; Bostrom, Mathias P. G.; Freeman, Theresa

    2015-01-01

    Objective Evaluation of early compositional changes in healing articular cartilage is critical for understanding tissue repair and for therapeutic decision-making. Fourier transform infrared imaging spectroscopy (FT-IRIS) can be used to assess the molecular composition of harvested repair tissue. Furthermore, use of an infrared fiber-optic probe (IFOP) has the potential for translation to a clinical setting to provide molecular information in situ. In the current study, we determined the feasibility of IFOP assessment of cartilage repair tissue in a rabbit model, and assessed correlations with gold-standard histology. Design Bilateral osteochondral defects were generated in mature white New Zealand rabbits, and IFOP data obtained from defect and adjacent regions at 2, 4, 6, 8, 12, and 16 weeks postsurgery. Tissues were assessed histologically using the modified O’Driscoll score, by FT-IRIS, and by partial least squares (PLS) modeling of IFOP spectra. Results The FT-IRIS parameters of collagen content, proteoglycan content, and collagen index correlated significantly with modified O’Driscoll score (P = 0.05, 0.002, and 0.02, respectively), indicative of their sensitivity to tissue healing. Repair tissue IFOP spectra were distinguished from normal tissue IFOP spectra in all samples by PLS analysis. However, the PLS model for prediction of histological score had a high prediction error, which was attributed to the spectral information being acquired from the tissue surface only. Conclusion The strong correlations between FT-IRIS data and histological score support further development of the IFOP technique for clinical applications, although further studies to optimize data collection from the full sample depths are required. PMID:26175863

  16. Multiphasic modeling of charged solute transport across articular cartilage: Application of multi-zone finite-bath model.

    PubMed

    Arbabi, Vahid; Pouran, Behdad; Weinans, Harrie; Zadpoor, Amir A

    2016-06-14

    Charged and uncharged solutes penetrate through cartilage to maintain the metabolic function of chondrocytes and to possibly restore or further breakdown the cartilage tissue in different stages of osteoarthritis. In this study the transport of charged solutes across the various zones of cartilage was quantified, taken into account the physicochemical interactions between the solute and the cartilage constituents. A multiphasic finite-bath finite element (FE) model was developed to simulate equine cartilage diffusion experiments that used a negatively charged contrast agent (ioxaglate) in combination with serial micro-computed tomography (micro-CT) to measure the diffusion. By comparing the FE model with the experimental data both the diffusion coefficient of ioxaglate and the fixed charge density (FCD) were obtained. In the multiphasic model, cartilage was divided into multiple (three) zones to help understand how diffusion coefficient and FCD vary across cartilage thickness. The direct effects of charged solute-FCD interaction on diffusion were investigated by comparing the diffusion coefficients derived from the multiphasic and biphasic-solute models. We found a relationship between the FCD obtained by the multiphasic model and ioxaglate partitioning obtained from micro-CT experiments. Using our multi-zone multiphasic model, diffusion coefficient of the superficial zone was up to ten-fold higher than that of the middle zone, while the FCD of the middle zone was up to almost two-fold higher than that of the superficial zone. In conclusion, the developed finite-bath multiphasic model provides us with a non-destructive method by which we could obtain both diffusion coefficient and FCD of different cartilage zones. The outcomes of the current work will also help understand how charge of the bath affects the diffusion of a charged molecule and also predict the diffusion behavior of a charged solute across articular cartilage.

  17. Fibrin sealants from fresh or fresh/frozen plasma as scaffolds for in vitro articular cartilage regeneration.

    PubMed

    Dare, Emma V; Griffith, May; Poitras, Philippe; Wang, Tao; Dervin, Geoffrey F; Giulivi, Antonio; Hincke, Maxwell T

    2009-08-01

    Our objective was to evaluate human CryoSeal fibrin glue derived from single units of plasma as scaffolds for articular cartilage tissue engineering. Human articular chondrocytes were encapsulated into genipin cross-linked fibrin glue derived from individual units of fresh or frozen plasma using the CryoSeal fibrin sealant (FS) system. The constructs were cultured for up to 7 weeks in vitro under low (5%) or normal (21%) oxygen. Chondrocyte viability was >90% within the fibrin gels. Hypoxia induced significant increases in collagen II and Sox9 gene expression and a significant decrease in collagen I. A significant increase in collagen II was detected in fresh plasma-derived cultures, while only collagen I was significantly increased in frozen plasma cultures. Significant increases in total glycosaminoglycan and collagen were detected in the extracellular matrix secreted by the encapsulated chondrocytes. A significant increase in compression modulus was only observed for fresh plasma-derived gels, which is likely explained by a greater amount of collagen type I detected after 7 weeks in frozen compared to fresh plasma gels. Our results indicate that CryoSeal fibrin glue derived from fresh plasma is suitable as a tissue engineering scaffold for human articular chondrocytes, and therefore should be evaluated for autologous articular cartilage regeneration.

  18. Deficiency of Thrombospondin-4 in Mice Does Not Affect Skeletal Growth or Bone Mass Acquisition, but Causes a Transient Reduction of Articular Cartilage Thickness

    PubMed Central

    Simon, Maciej; Peters, Stephanie; Baum, Wolfgang; Schett, Georg; Ruether, Wolfgang; Niemeier, Andreas; Schinke, Thorsten; Amling, Michael

    2015-01-01

    Although articular cartilage degeneration represents a major public health problem, the underlying molecular mechanisms are still poorly characterized. We have previously utilized genome-wide expression analysis to identify specific markers of porcine articular cartilage, one of them being Thrombospondin-4 (Thbs4). In the present study we analyzed Thbs4 expression in mice, thereby confirming its predominant expression in articular cartilage, but also identifying expression in other tissues, including bone. To study the role of Thbs4 in skeletal development and integrity we took advantage of a Thbs4-deficient mouse model that was analyzed by undecalcified bone histology. We found that Thbs4-deficient mice do not display phenotypic differences towards wildtype littermates in terms of skeletal growth or bone mass acquisition. Since Thbs4 has previously been found over-expressed in bones of Phex-deficient Hyp mice, we additionally generated Thbs4-deficient Hyp mice, but failed to detect phenotypic differences towards Hyp littermates. With respect to articular cartilage we found that Thbs4-deficient mice display transient thinning of articular cartilage, suggesting a protective role of Thbs4 for joint integrity. Gene expression analysis using porcine primary cells revealed that Thbs4 is not expressed by synovial fibroblasts and that it represents the only member of the Thbs gene family with specific expression in articular, but not in growth plate chondrocytes. In an attempt to identify specific molecular effects of Thbs4 we treated porcine articular chondrocytes with human THBS4 in the absence or presence of conditioned medium from porcine synovial fibroblasts. Here we did not observe a significant influence of THBS4 on proliferation, metabolic activity, apoptosis or gene expression, suggesting that it does not act as a signaling molecule. Taken together, our data demonstrate that Thbs4 is highly expressed in articular chondrocytes, where its presence in the

  19. Effects of an aqueous extract of Eucommia on articular cartilage in a rat model of osteoarthritis of the knee.

    PubMed

    Lu, Hai; Jiang, Jianming; Xie, Guoping; Liu, Wengang; Yan, Guangbin

    2013-09-01

    Osteoarthritis is a common chronic and progressively degenerative joint condition. The stem bark of Eucommia ulmoides Oliver (a member of the Eucommiaceae family), which is also known as Du-Zhong, is a traditional Chinese medicine commonly used for the treatment of rheumatoid arthritis. However, the mechanisms underlying the effects of Eucommia in the treatment of arthritis of the knee require further study. The present study investigated the effects of an aqueous extract of Eucommia on the articular cartilage (by Mankin's grade) and the levels of matrix metalloproteinase-1 (MMP-1), MMP-3 and MMP-13 in the serum and synovial fluid in a rat model of osteoarthritis. The serum levels of MMP-1, -3 and -13 were measured by double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) at weeks 1, 2 and 4. The levels of MMP-1, -3 and 13 were significantly decreased in the rats treated with Eucommia compared with those in the control rats (P<0.05). Histopathological examination results indicated a lower Mankin's grade in the Eucommia group compared with that of the control rats. Therefore, Eucommia was demonstrated to have a cartilage-protecting effect in rats with osteoarthritis, potentially by improving cartilage metabolism, regulating the degradation of the extracellular matrix of the articular cartilage, and inhibiting apoptosis in chondrocytes, thereby slowing down joint degeneration.

  20. Pathology of articular cartilage and synovial membrane from elbow joints with and without degenerative joint disease in domestic cats.

    PubMed

    Freire, M; Meuten, D; Lascelles, D

    2014-09-01

    The elbow joint is one of the feline appendicular joints most commonly and severely affected by degenerative joint disease. The macroscopic and histopathological lesions of the elbow joints of 30 adult cats were evaluated immediately after euthanasia. Macroscopic evidence of degenerative joint disease was found in 22 of 30 cats (39 elbow joints) (73.33% cats; 65% elbow joints), and macroscopic cartilage erosion ranged from mild fibrillation to complete ulceration of the hyaline cartilage with exposure of the subchondral bone. Distribution of the lesions in the cartilage indicated the presence of medial compartment joint disease (most severe lesions located in the medial coronoid process of the ulna and medial humeral epicondyle). Synovitis scores were mild overall and correlated only weakly with macroscopic cartilage damage. Intra-articular osteochondral fragments either free or attached to the synovium were found in 10 joints. Macroscopic or histologic evidence of a fragmented coronoid process was not found even in those cases with intra-articular osteochondral fragments. Lesions observed in these animals are most consistent with synovial osteochondromatosis secondary to degenerative joint disease. The pathogenesis for the medial compartmentalization of these lesions has not been established, but a fragmented medial coronoid process or osteochondritis dissecans does not appear to play a role.

  1. Effects of holmium:YAG laser on equine articular cartilage and subchondral bone adjacent to traumatic lesions

    NASA Astrophysics Data System (ADS)

    Collier, Michael A.; Haugland, L. Mark; Bellamy, Janine; Johnson, Lanny L.; Rohrer, Michael D.; Walls, Robert C.; Bartels, Kenneth E.

    1994-09-01

    The effects of Ho:YAG laser energy on articular cartilage and subchondral bone adjacent to traumatically created cartilage lesions in a continuous weight-bearing model were investigated. The 2.1 micrometers wavelength was delivered in hand-controlled contact and near-contact hard tissue arthroscopic surgery in a saline medium. Bilateral arthroscopy was performed on normal antebrachiocarpal and intercarpal joints of four adult horses. One-hundred twenty traumatic lesions were created on three weight-bearing articular surfaces with a knife, curette, or a motorized burr. Depths of the lesions were partial and full thickness. Configurations of the lesions were lacerations, scrapes, and craters. Left limbs were used as controls. Right limb lesions were treated with various intensities of laser energy. Animals were sacrificed at intervals of 1, 3, and 8 weeks. Gross microscopic anatomy was documented, and tissue sections were subjected to blind review by a pathologist. Mankin grading for cellularity and proteoglycan content was used to qualitatively evaluate cartilage response. Cartilage adjacent to all lesions exposed to laser energy had better cellularity and proteoglycan content than corresponding controls by Mankin grading.

  2. Surface zone articular chondrocytes modulate the bulk and surface mechanical properties of the tissue-engineered cartilage.

    PubMed

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

    2014-12-01

    The central hypothesis of functional tissue engineering is that an engineered construct can serve as a viable replacement tissue in vivo by replicating the structure and function of native tissue. In the case of articular cartilage, this requires the reproduction of the bulk mechanical and surface lubrication properties of native hyaline cartilage. Cartilage tissue engineering has primarily focused on achieving the bulk mechanical properties of native cartilage such as the compressive aggregate modulus and tensile strength. A scaffold-free self-assembling process has been developed that produces engineered cartilage with compressive properties approaching native tissue levels. Thus, the next step in this process is to begin addressing the friction coefficient and wear properties of these engineered constructs. The superficial zone protein (SZP), also known as lubricin or PRG4, is a boundary mode lubricant that is synthesized by surface zone (SZ) articular chondrocytes. Under conditions of high loading and low sliding speeds, SZP reduces friction and wear at the articular surface. The objective of this investigation was to determine whether increasing the proportion of SZ chondrocytes in cartilage constructs, in the absence of external stimuli such as growth factors and mechanical loading, would enhance the secretion of SZP and improve their frictional properties. In this study, cartilage constructs were engineered through a self-assembling process with varying ratios of SZ and middle zone (MZ) chondrocytes (SZ:MZ): 0:100, 25:75, 50:50, 75:25, and 100:0. Constructs containing different ratios of SZ and MZ chondrocytes did not significantly differ in the glycosaminoglycan composition or compressive aggregate modulus. In contrast, tensile properties and collagen content were enhanced in nearly all constructs containing greater amounts of SZ chondrocytes. Increasing the proportion of SZ chondrocytes had the hypothesized effect of improving the synthesis and secretion

  3. Partial reversal by beta-D-xyloside of salicylate-induced inhibition of glycosaminoglycan synthesis in articular cartilage

    SciTech Connect

    Palmoski, M.J.; Brandt, K.D.

    1982-09-01

    While net /sup 35/S-glycosaminoglycan synthesis in normal canine articular cartilage was suppressed by 10(-3)M sodium salicylate to about 70% of the control value, addition of xyloside (10(-6)M-10(-3)M) to the salicylate-treated cultures led to a concentration-dependent increase in glycosaminoglycan synthesis, which rose to 120-237% of controls. Similar results were obtained when /sup 3/H-glucosamine was used to measure glycosaminoglycan synthesis, confirming that salicylate suppresses and xyloside stimulates net glycosaminoglycan synthesis, and not merely sulfation. Salicylate (10-3)M) did not affect the activity of xylosyl or galactosyl transferase prepared from canine knee cartilage, and net protein synthesis was unaltered by either salicylate or xyloside. The proportion of newly synthesized proteoglycans existing as aggregates when cartilage was cultured with xyloside was similar to that in controls, although the average hydrodynamic size of disaggregated proteoglycans and of sulfated glycosaminoglycans was diminished.

  4. Determination of the collagen fiber `brushing direction' in articular cartilage by conical-scan polarization-sensitive optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Lu, Zenghai; Kasaragod, Deepa; Matcher, Stephen J.

    2014-03-01

    A new imaging technique is presented by introducing the concept of conical scan to the variable-incidenc-angle polarimetry (VIA) previously developed by our group. The technique would facilitate the translating of the VIA technique to the clinic by simplifying the requirements of measurements in two orthogonal planes by using a conical scan protocol. Conical scan PS-OCT images could illustrate directly the azimuthal angle of the collage fibers in birefringent tissue, which was validated by measurements on a bovine tendon. We have showed the unique technique can be used to locate the "brushing direction" of collagen fibers in articular cartilage. Measuring this direction over the cartilage surface could potentially help designing of tissue-engineering scaffolds for cartilage repair.

  5. Determining equilibrium osmolarity in poly(ethylene glycol)/chondrotin sulfate gels mimicking articular cartilage.

    PubMed

    Sircar, S; Aisenbrey, E; Bryant, S J; Bortz, D M

    2015-01-07

    We present an experimentally guided, multi-phase, multi-species polyelectrolyte gel model to make qualitative predictions on the equilibrium electro-chemical properties of articular cartilage. The mixture theory consists of two different types of polymers: poly(ethylene gylcol) (PEG), chondrotin sulfate (ChS), water (acting as solvent) and several different ions: H(+), Na(+), Cl(-). The polymer chains have covalent cross-links whose effect on the swelling kinetics is modeled via Doi rubber elasticity theory. Numerical studies on equilibrium polymer volume fraction and net osmolarity (difference in the solute concentration across the gel) show a complex interplay between ionic bath concentrations, pH, cross-link fraction and the average charge per monomer. Generally speaking, swelling is aided due to a higher average charge per monomer (or a higher particle fraction of ChS, the charged component of the polymer), low solute concentration in the bath, a high pH or a low cross-link fraction. A peculiar case arises at higher values of cross-link fraction, where it is observed that increasing the average charge per monomer leads to gel deswelling.

  6. Highly Porous Gelatin Reinforced 3D Scaffolds for Articular Cartilage Regeneration.

    PubMed

    Amadori, Sofia; Torricelli, Paola; Panzavolta, Silvia; Parrilli, Annapaola; Fini, Milena; Bigi, Adriana

    2015-07-01

    3D highly porous (93% total porosity) gelatin scaffolds were prepared according to a novel, simple method, which implies gelatin foaming, gelification, soaking into ethanol and successive freeze-drying. Reinforcement of the as-prepared scaffolds (GEL) was performed through immersion in aqueous solutions at different gelatin concentrations. Reinforcement solutions with and without genipin addition allowed to prepare two series of samples:cross-linked and uncross-linked samples, respectively. The amount of gelatin adsorbed onto the reinforced samples increases as a function of gelatin concentration in solution and provokes a drastic improvement of the compressive modulus and collapse strength up to values of about 30 and 4 MPa, respectively. The open and interconnected porosity, although slightly reduced, is still of the order of 80% in the samples reinforced with the highest concentration of gelatin. Water uptake ability evaluated after immersion in PBS for 20 s decreases with gelatin reinforcement. The presence of genipin in cross-linked samples reduces gelatin release and stabilizes the scaffolds in solution. Chondrocytes from human articular cartilage adhere, proliferate, and penetrate into the scaffolds. The evaluation of differentiation markers both on the supernatants of cell culture and by means of quantitative polymerase chain reaction (qPCR) indicates a dose-dependent promotion of cell differentiation.

  7. Characterization of a polyvinyl alcohol-hydrogel artificial articular cartilage prepared by injection molding.

    PubMed

    Kobayashi, Masanori; Oka, Masanori

    2004-01-01

    We have developed a hip hemi-arthroplasty using polyvinyl alcohol-hydrogel (PVA-H) as the treatment for hip joint disorders in which the lesion is limited to the joint surface. In previous studies, we characterized the biocompatibility and the mechanical properties of PVA-H as an arthroplasty material. To fix PVA-H firmly to the bone, we have devised an implant composed of PVA-H and porous titanium fiber mesh (TFM). However, because of poor infiltration of the PVA solution into the pores of the TFM when using the low temperature crystallization method, the strength of the PVA-H-TFM interface was insufficient. Consequently, the infiltration method was improved by adopting high-pressure injection molding. With this improved method, the bonding strength of the interface increased remarkably. However, as this injection molding requires high temperature, various mechanical properties of the PVA-H might change with this treatment in comparison with the previous method. The purpose of this study was to investigate the effect of high temperature treatment on the mechanical properties of PVA-H as artificial articular cartilage, the tensile test and friction test were performed about new PVA-H. The results showed no significant mechanical deterioration of the PVA-H. This certified that the injection-molding method did not induce the change of the mechanical properties of PVA-H and indicated the potential of hemi-arthroplasty using PVA-H by this method in the future.

  8. Proteoglycans in articular cartilage revealed with a quick freezing and deep etching method.

    PubMed Central

    Toriumi, H; Nakagawa, H; Ueda, H; Leng, C G; Fujii, Y; Ohno, S

    1996-01-01

    OBJECTIVES: To clarify the three dimensional ultrastructure of proteoglycans, and their relationship with other matrix components in articular cartilage. METHODS: Specimens from rat femoral heads were examined using three techniques: (1) Histochemical staining with cationic polyethyleneimine (PEI), using a pre-embedding or a postembedding method. Some tissues were pretreated with chondroitinase ABC or hyaluronidase. (2) Quick freezing and deep etching (QF-DE). Some specimens were fixed with paraformaldehyde and washed in buffer solution before quick freezing; others were frozen directly. (3) Ultrathin sections were studied after conventional preparation. RESULTS: Proteoglycans were observed as aggregated clumps with PEI staining by the pre-embedding method, but as fine filaments by the postembedding method. They were lost with enzyme digestion; this was also demonstrated by the QF-DE method. The ultrastructure was well preserved by the QF-DE method when fixation and washing procedures were included, but not without these procedures. A fine mesh-like structure was connected to the cell membrane in the pericellular matrix. Filamentous structures suggestive of aggrecans were observed among collagen fibrils. They had side chains, approximately 50 nm in length, which branched from the central filaments at intervals of 10-20 nm, and were occasionally linked to other structures. Many thin filaments were also attached to the collagen fibrils. CONCLUSIONS: The QF-DE method incorporating paraformaldehyde fixation and buffer washing procedures revealed three dimensional, extended structures suggestive of proteoglycans. Images PMID:8774166

  9. Cell compaction influences the regenerative potential of passaged bovine articular chondrocytes in an ex vivo cartilage defect model.

    PubMed

    Schmutzer, Michael; Aszodi, Attila

    2017-04-01

    The loss and degradation of articular cartilage tissue matrix play central roles in the process of osteoarthritis (OA). New models for evaluating cartilage repair/regeneration are thus of great value for transferring various culture systems into clinically relevant situations. The repair process can be better monitored in ex vivo systems than in in vitro cell cultures. I have therefore established an ex vivo defect model prepared from bovine femoral condyles for evaluating cartilage repair by the implantation of cells cultured in various ways, e.g., monolayer-cultured cells or suspension or pellet cultures of articular bovine chondrocytes representing different cell compactions with variable densities of chondrocytes. I report that the integrin subunit α10 was significantly upregulated in suspension-cultured bovine chondrocytes at passage P2 compared with monolayer-cultured cells at P1 (p = 0.0083) and P2 (p < 0.05). Suspension-cultured cells did not promote cartilage repair when compared with implanted monolayer-cultured chondrocytes and pellets: 24.0 ± 0.66% for suspension cells, 46.4 ± 2.9% for monolayer cells, and 127.64 ± 0.90% for pellets (p < 0.0001) of the original defect volume (percentage of defect). Additional cultivation with chondrogenesis-promoting growth factors TGF-β1 and BMP-2 revealed an enhancing effect on cartilage repair in all settings. The advantage and innovation of this system over in vitro differentiation (e.g., micromass, pellet) assays is the possibility of examining and evaluating cartilage regeneration in an environment in which implanted cells are embedded within native surrounding tissue at the defect site. Such ex vivo explants might serve as a better model system to mimic clinical situations.

  10. Clinical platform for understanding the relationship between joint contact mechanics and articular cartilage changes after meniscal surgery.

    PubMed

    Maher, Suzanne A; Wang, Hongsheng; Koff, Matthew F; Belkin, Nicole; Potter, Hollis G; Rodeo, Scott A

    2017-03-01

    Injury to the meniscus of the knee has been implicated as a significant risk factor for the subsequent development of osteoarthritis, but the mechanisms of joint degeneration are unclear. Our objective was to develop a clinically applicable methodology to evaluate the relationship of joint contact mechanics at the time of surgery to biological changes of articular cartilage as a function of time following surgery. A series of pre-, intra-, and post-operative protocols were developed which utilized electronic sensors for the direct measurement of contact mechanics, and advanced imaging to assess cartilage health. The tests were applied to a pilot cohort of young active patients undergoing meniscus allograft transplantation. Our study demonstrated significant variability across patients in terms of contact area and peak contact stress, both before and after transplantation. Nonetheless, the majority of patients exhibited decreased peak contact stress and increased contact area after graft implantation. MR scans at 3-6 months showed decreased T1ρ values in tibial articular cartilage, suggesting an increase in proteoglycan content or concomitant decrease in water content. Prolongation of T2 values was found primarily within the central, cartilage-cartilage contact region of the tibial plateau suggested disruption of the collagen network. Minimal differences were found in cartilage thickness over the short time frame of this preliminary study. With longer clinical follow-up, our platform of clinical tests can be used to better understand the patient-specific mechanical factors that are related to increased risk of OA after meniscus injury and surgery. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:600-611, 2017.

  11. Cartilage issues in football—today's problems and tomorrow's solutions

    PubMed Central

    Mithoefer, Kai; Peterson, Lars; Zenobi-Wong, Marcy; Mandelbaum, Bert R

    2015-01-01

    Articular cartilage injury is prevalent in football players and results from chronic joint stress or acute traumatic injuries. Articular cartilage injury can often result in progressive painful impairment of joint function and limit sports participation. Management of articular cartilage injury in athletes aims to return the player to competition, and requires effective and durable joint surface restoration that resembles normal hyaline articular cartilage that can withstand the high joint stresses of football. Existing articular cartilage repair techniques can return the athlete with articular cartilage injury to high-impact sports, but treatment does not produce normal articular cartilage, and this limits the success rate and durability of current cartilage repair in athletes. Novel scientific concepts and treatment techniques that apply modern tissue engineering technologies promise further advancement in the treatment of these challenging injuries in the high demand athletic population. We review the current knowledge of cartilage injury pathophysiology, epidemiology and aetiology, and outline existing management algorithms, developing treatment options and future strategies to manage articular cartilage injuries in football players. PMID:25878075

  12. A single intra-articular injection with IL-4 plus IL-10 ameliorates blood-induced cartilage degeneration in haemophilic mice.

    PubMed

    van Meegeren, Monique E R; Roosendaal, Goris; Coeleveld, Katja; Nieuwenhuizen, Laurens; Mastbergen, Simon C; Lafeber, Floris P J G

    2013-02-01

    The combination of interleukin (IL)-4 and IL-10 protects against blood-induced cartilage damage in vitro. It has been hypothesized that the combination of these cytokines is effective if applied early in the process of cartilage damage. The present study investigated whether a single intra-articular injection of IL-4 plus IL-10 immediately after a joint bleed limits cartilage damage in an in vivo haemophilia mouse model of blood-induced joint damage. Factor VIII knockout mice with severe haemophilia A were punctured once with a needle below the patella to induce a joint haemorrhage. Subsequently IL-4 plus IL-10 (n = 24) or vehicle (n = 24) was injected intra-articularly. After 35 days, the time needed for development of detectable joint degeneration, knee joints were examined for cartilage damage by macroscopic and microscopic evaluation. A single intra-articular injection of IL-4 plus IL-10 ameliorated progression of cartilage degeneration caused by a single joint bleed to a certain extent. No effect on inflammation was observed at this time point. A single intra-articular injection of IL-4 plus Il-10 directly after a single joint bleed limits progression of cartilage degeneration over time. Improved bioavailability (half-life) of both cytokines might improve their protective ability in the development of cartilage degeneration, and probably also inflammation.

  13. A Review of the Combination of Experimental Measurements and Fibril-Reinforced Modeling for Investigation of Articular Cartilage and Chondrocyte Response to Loading

    PubMed Central

    Wilson, Wouter; Isaksson, Hanna; Jurvelin, Jukka S.; Herzog, Walter; Korhonen, Rami K.

    2013-01-01

    The function of articular cartilage depends on its structure and composition, sensitively impaired in disease (e.g. osteoarthritis, OA). Responses of chondrocytes to tissue loading are modulated by the structure. Altered cell responses as an effect of OA may regulate cartilage mechanotransduction and cell biosynthesis. To be able to evaluate cell responses and factors affecting the onset and progression of OA, local tissue and cell stresses and strains in cartilage need to be characterized. This is extremely challenging with the presently available experimental techniques and therefore computational modeling is required. Modern models of articular cartilage are inhomogeneous and anisotropic, and they include many aspects of the real tissue structure and composition. In this paper, we provide an overview of the computational applications that have been developed for modeling the mechanics of articular cartilage at the tissue and cellular level. We concentrate on the use of fibril-reinforced models of cartilage. Furthermore, we introduce practical considerations for modeling applications, including also experimental tests that can be combined with the modeling approach. At the end, we discuss the prospects for patient-specific models when aiming to use finite element modeling analysis and evaluation of articular cartilage function, cellular responses, failure points, OA progression, and rehabilitation. PMID:23653665

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

    PubMed

    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.

  15. Development of a noninvasive multifunctional measurement method using nanosecond pulsed laser for evaluation of regenerative medicine for articular cartilage

    NASA Astrophysics Data System (ADS)

    Ishihara, Miya; Sato, Masato; Kaneshiro, Nagatoshi; Mitani, Genya; Sato, Shunichi; Ishihara, Masayuki; Mochida, Joji; Kikuchi, Makoto

    2006-02-01

    We demonstrated the capability of a photoacoustic method for viscoelastic measurement. The measurement method has already proved to be useful for evaluation of regenerative medicine of articular cartilage. However, characterization of the extracellular matrix as well as determination of the viscoelastic property should be carried out for evaluation of regenerative medicine because the extracellular matrix plays an important role. We therefore developed a method for characterization of the extracellular matrix that can be performed simultaneously with the photoacoustic measurement. Since collagen molecules, which are the major contents of the cartilage extracellular matrix, are well known as endogenous fluorescent molecules, it is possible that fluorescence measurement will enable characterization of the extracellular matrix. Third harmonic Q-switched Nd:YAG laser pulses were used as an excitation light source. The time-resolved fluorescence spectroscopy was obtained by using a photonic multi-channel analyzer. Tissue-engineered cartilages cultured under different conditions for various periods were used as samples. Different culture conditions resulted in different extracellular matrix formations. There were significant differences in the measured fluorescent parameters among the culture conditions of cartilage because chondrocytes produce a specific extracellular matrix depending on its culture condition. The specific extracellular matrix contained a specific type of collagen such as collagen type I or type II, which each have specific fluorescent features. Thus, the fluorescent parameters enabled characterization of synthesis of cartilage-associated extracellular matrix. Therefore, the combination of fluorescence and photoacoustic measurement is expected to become a useful evaluation method in regenerative medicine.

  16. Suppression of adverse angiogenesis in an albumin-based hydrogel for articular cartilage and intervertebral disc regeneration.

    PubMed

    Scholz, B; Kinzelmann, C; Benz, K; Mollenhauer, J; Wurst, H; Schlosshauer, B

    2010-07-13

    An injectable polyethylene glycol-crosslinked albumin gel (AG) supplemented with hyaluronic acid as a matrix for autologous chondrocyte implantation was evaluated with regard to its impact on angiogenesis. Healthy articular cartilage and intervertebral discs (IVD) are devoid of blood vessels, whereas pathological blood vessel formation augments degeneration of both theses tissues. In contrast to human endothelial cells, primary human articular chondrocytes encapsulated in the AG retained their viability. Endothelial cells did not adhere to the gel surface to a significant extent nor did they proliferate in vitro. The AG did not release any diffusible toxic components. Contrary to Matrigel employed as positive control, the AG prevented endothelial chemoinvasion in Transwell filter assays even in the presence of a chemotactic gradient of vascular endothelial growth factor. In ovo, the AG exhibited a barrier function for blood vessels of the chick chorioallantoic membrane. Subcutaneous implantation of human IVD chondrocytes enclosed in the albumin gel into immunodeficient mice revealed a complete lack of angiogenesis inside the gel after two weeks. At the same time, the IVD chondrocytes within the gel remained vital and displayed a characteristic gene expression pattern as judged from aggrecan, collagen type I and type II mRNA levels. In summary, aiming at articular cartilage and IVD regeneration the albumin gel promises to be a beneficial implant matrix for chondrocytes simultaneously exhibiting non-permissive properties for adverse endothelial cells.

  17. Trabecular Bone Structure and Spatial Differences in Articular Cartilage MR Relaxation Times in Individuals with Posterior Horn Medial Meniscal Tears

    PubMed Central

    Kumar, Deepak; Schooler, Joseph; Zuo, Jin; McCulloch, Charles E.; Nardo, Lorenzo; Link, Thomas M.; Li, Xiaojuan; Majumdar, Sharmila

    2012-01-01

    Objective To analyze knee trabecular bone structure and spatial cartilage T1ρ and T2 relaxation times using 3-T MRI in subjects with and without tears of posterior horn of medial meniscus (PHMM). Design 3-T MRI from 59 subjects (> 18 years), were used to evaluate PHMM tears based on modified WORMS scoring; and to calculate apparent trabecular bone - volume over total bone volume fraction (app. BV/TV), number (app. Tb.N), separation (app. Tb.Sp) and thickness (app. Tb.Th) for overall femur/tibia and medial/lateral femur/tibia; and relaxation times for deep and superficial layers of articular cartilage. A repeated measures analysis using GEE was performed to compare trabecular bone and cartilage relaxation time parameters between people with (n = 35) and without (n= 24) PHMM tears, while adjusting for age and knee OA presence. Results Subjects with PHMM tears had lower app. BV./TV and app. Tb.N, and greater app. Tb.Th, and app. Tb.Sp. They also had higher T1ρ times in the deep cartilage layer for lateral tibia and medial femur and higher T2 relaxation times for the deep cartilage layer across all compartments. Conclusions PHMM tears are associated with differences in underlying trabecular bone and deep layer of cartilage. Overload of subchondral bone can lead to its sclerosis and stress shielding of trabecular bone leading to the resorptive changes observed in this study. The results underline the importance of interactions of trabecular bone and cartilage in the pathogenesis of knee OA in people with PHMM tears. PMID:23047010

  18. Experimental study on the role of intra-articular injection of MSCs on cartilage regeneration in haemophilia.

    PubMed

    Ravanbod, R; Torkaman, G; Mophid, M; Mohammadali, F

    2015-09-01

    Mesenchymal stem cells (MSCs) therapy is a field in progress in cartilage repair strategies. We tried to investigate the functional properties of the joint and cartilage in experimental haemarthrosis (EH) after MSCs intra-articular (IA) injection. One millilitre of fresh autologous blood was injected twice a week for three consecutive weeks in three groups including control haemophilia 10 days (n = 8), control haemophilia 38 days (n = 8) and MSCs (n = 8) group. In later, 10 days after the end of IA blood injections, MSCs IA injection was performed. Eight animals received no treatment as the normal control group. Thirty-eight days after the end of IA blood injections, animals were sacrificed. Joint friction and stress-relaxation tests were done, inflammatory cytokines of synovial membrane and scanning electron microscopy of the cartilage assessed. Joint friction decreased in MSCs in comparison to other groups and was significant with normal control group, (P = 0.011). The mechanical properties of cartilage showed no significant differences between groups. Tumour necrosis factor alpha and interleukin 1 beta decreased and IL-4 very slightly increased in MSCs in comparison to the time-matched control group. Scanning electron microscopy enabled acquisition of good structural properties of the surface and layers of the cartilage after MSCs injection. The hole induced in the medial plateau of the tibia bones, after inducing haemarthrosis, were covered with cartilage-like structure. The results showed that MSCs IA injection has some beneficial effects on cartilage structure and function in haemarthrosis model and is promising in patients with haemophilia.

  19. Reactive nitrogen species scavenging, rather than nitric oxide inhibition, protects from articular cartilage damage in rat zymosan-induced arthritis

    PubMed Central

    Bezerra, Mirna Marques; Brain, Susan D; Greenacre, Stan; Jerônimo, Selma Maria Bezerra; de Melo, Liana Batista; Keeble, Julie; da Rocha, Francisco Airton Castro

    2003-01-01

    The contribution of nitric oxide (NO) and peroxynitrite (PN) to inflammation in a zymosan-induced (1 mg, intra-articular, i.art.) rat model of arthritis was assessed by histopathology and by measuring the glycosaminoglycan (GAG) content of the articular cartilage. Progression of the chronic synovitis in zymosan-induced arthritis (ZYA) was associated with increased nitrite and nitrotyrosine (3-NT) levels in the joint exudates that paralleled a progressive loss of the GAG content. An increase in 3-NT was also observed after i.art. PN. The nonselective nitric oxide synthase (NOS) inhibitor L-NG-nitroarginine methyl ester (25–75 mg kg−1day−1) or the selective inducible NOS inhibitor aminoguanidine (50–100 mg kg−1day−1) given 1 h before (prophylactic) or 3 days after (therapeutic) injection of the zymosan ameliorated the synovitis, but worsened the GAG loss, as measured at the end of the experiment (day 7). The PN scavenger uric acid (100–250 mg kg−1 i.p. four times daily) given prophylactically until the end of the experiment (day 14), in a dose compatible with its PN scavenging activity, significantly decreased both the synovitis and the GAG loss. In conclusion, PN formation is associated with cartilage damage in addition to proinflammatory activity in ZYA. NOS inhibitors and a PN scavenger were able to reduce the cellular infiltration, while displaying opposite effects on cartilage homeostasis either by enhancing or ameliorating the damage, respectively. PMID:14662723

  20. The role of flow-independent viscoelasticity in the biphasic tensile and compressive responses of articular cartilage.

    PubMed

    Huang, C Y; Mow, V C; Ateshian, G A

    2001-10-01

    A long-standing challenge in the biomechanics of connective tissues (e.g., articular cartilage, ligament, tendon) has been the reported disparities between their tensile and compressive properties. In general, the intrinsic tensile properties of the solid matrices of these tissues are dictated by the collagen content and microstructural architecture, and the intrinsic compressive properties are dictated by their proteoglycan content and molecular organization as well as water content. These distinct materials give rise to a pronounced and experimentally well-documented nonlinear tension-compression stress-strain responses, as well as biphasic or intrinsic extracellular matrix viscoelastic responses. While many constitutive models of articular cartilage have captured one or more of these experimental responses, no single constitutive law has successfully described the uniaxial tensile and compressive responses of cartilage within the same framework. The objective of this study was to combine two previously proposed extensions of the biphasic theory of Mow et al. [1980, ASME J. Biomech. Eng., 102, pp. 73-84] to incorporate tension-compression nonlinearity as well as intrinsic viscoelasticity of the solid matrix of cartilage. The biphasic-conewise linear elastic model proposed by Soltz and Ateshian [2000, ASME J. Biomech. Eng., 122, pp. 576-586] and based on the bimodular stress-strain constitutive law introduced by Curnier et al. [1995, J. Elasticity, 37, pp. 1-38], as well as the biphasic poroviscoelastic model of Mak [1986, ASME J. Biomech. Eng., 108, pp. 123-130], which employs the quasi-linear viscoelastic model of Fung [1981, Biomechanics: Mechanical Properties of Living Tissues, Springer-Verlag, New York], were combined in a single model to analyze the response of cartilage to standard testing configurations. Results were compared to experimental data from the literature and it was found that a simultaneous prediction of compression and tension experiments of

  1. Cyclooxygenases (COX-1 and COX-2) for tissue engineering of articular cartilage--from a developmental model to first results of tissue and scaffold expression.

    PubMed

    Brochhausen, Christoph; Zehbe, Rolf; Gross, Ulrich; Libera, Jeanette; Schubert, Helmut; Nüsing, Rolf M; Klaus, Günter; Kirkpatrick, C James

    2008-01-01

    Tissue engineering of articular cartilage remains an ongoing challenge. Since tissue regeneration recapitulates ontogenetic processes the growth plate can be regarded as an innovative model to target suitable signalling molecules and growth factors for the tissue engineering of cartilage. In the present study we analysed the expression of cyclooxygenases (COX) in a short-term chondrocyte culture in gelatin-based scaffolds and in articular cartilage of rats and compared it with that in the growth plate. Our results demonstrate the strong cellular expression of COX-1 but only a focal weak expression of COX-2 in the seeded scaffolds. Articular cartilage of rats expresses homogeneously COX-1 and COX-2 with the exception of the apical cell layer. Our findings indicate a functional role of COX in the metabolism of articular chondrocytes. The expression of COX in articular cartilage and in the seeded scaffolds opens interesting perspectives to improve the proliferation and differentiation of chondrocytes in scaffold materials by addition of specific receptor ligands of the COX system.

  2. Mechanical effects of ionic replacements in articular cartilage. Part I: The constitutive model.

    PubMed

    Loret, Benjamin; Simões, Fernando M F

    2005-11-01

    A three-phase multi-species electro-chemo-mechanical model of articular cartilage is developed that accounts for the effect of two water compartments, namely intra-fibrillar water stored in between collagen fibrils and extra-fibrillar water covering proteoglycans. The collagen fibers constitute the solid phase while intra-fibrillar water and dissolved NaCl and CaCl(2) on one hand and extra-fibrillar water, ions Na(+), Ca(2+) and Cl(-) and proteoglycans on the other hand, form the two fluid phases. The complete picture that includes time-dependent mass transfers between the two fluid phases, diffusion of water and ions and electrical flow emerges from the Clausius-Duhem inequality but it is deferred to further study. The analysis is restricted to equilibrium states. The present work complements the mechanical model developed in Loret and Simões (Mech Material 36(5-6): 515-541, 2004a) where the presence of the sole NaCl was considered. In its current version, the model can handle mechanical and chemical loadings and unloadings involving the two salts, NaCl and CaCl(2). In order to reproduce experimental data, the shielding effects are made cation-dependent. Strong orientation of collagen fibers parallel to the joint surface implies anisotropic mechanical properties. Electro-chemo-mechanical couplings result in a chemistry-dependent apparent tensile Poisson's ratio, that increases to large values as the solution gets fresher. The model captures these aspects as well. The features of the model are first exposed in an infinitesimal strain context. Subsequently, large strains that typically occur in uniaxial traction under deionized water are accounted for, and a nonlinear anisotropic hyper-elastic behavior is developed. Parametric identification and simulations of actual loading processes are described in a companion paper, Loret and Simões (Biomech Model Mechanobiol, in press, DOI 10.1007/s10237-004-0063-6).

  3. The effect of supplementation of a glutamine precursor on the growth plate, articular cartilage and cancellous bone in fundectomy-induced osteopenic bone

    PubMed Central

    TOMASZEWSKA, Ewa; DOBROWOLSKI, Piotr; PROST, Łukasz; HUŁAS-STASIAK, Monika; MUSZYŃSKI, Siemowit; BLICHARSKI, Tomasz

    2015-01-01

    The aim of the study was to investigate the effect of 2-oxoglutaric acid (2-Ox) supplementation (a precursor of glutamine and hydroxyproline, the most abundant amino acid of collagen) on cartilage and bone in pigs after fundectomy. Pigs at the age of forty days were subjected to fundectomy and divided into two groups depending on 2-Ox supplementation (at the daily dosage of 0.4 g/kg of body weight). Other pigs were sham operated. Pigs were euthanized at the age of eight months. An analysis of the morphometry of trabeculae, growth plate and articular cartilage in fundectomy-induced osteopenic bone was performed. Moreover, the levels of expression of osteocalcin, osteopontin and osteoprotegerin in trabecular bone and osteocalcin in articular cartilage were evaluated. Articular cartilage was thinnest in fundectomized pigs and thickest in 2-Ox-supplemented animals after fundectomy. Moreover, 2-Ox supplementation after fundectomy enhanced the total thickness of the growth plate and trabeculae in fundectomized pigs. The most evident signal for osteocalcin and osteoprotegerin in trabecular bone was in sham-operated and 2-Ox-supplemented pigs; a low reaction was observed in the fundectomized group. Additionally, as a long-term postoperative consequence, a change was observed in the expression of osteocalcin in articular cartilage. It seems that 2-Ox is suitable for use in preventing the negative effects of fundectomy on cancellous bone and cartilage. PMID:26725871

  4. Spaceflight-Relevant Challenges of Radiation and/or Reduced Weight Bearing Cause Arthritic Responses in Knee Articular Cartilage.

    PubMed

    Willey, J S; Kwok, A T; Moore, J E; Payne, V; Lindburg, C A; Balk, S A; Olson, J; Black, P J; Walb, M C; Yammani, R R; Munley, M T

    2016-10-01

    acute degenerative and pre-arthritic changes in the knee articular cartilage of rats. A return to normal weight bearing resulted in some recovery from cartilage degradation. However, radiation delivered as both a single challenge and when combined with HLU resulted in chronic cartilage damage. These findings suggest that radiation exposure during spaceflight leads to and/or impairs recovery of cartilage upon return to reloading, generating long-term joint problems for astronauts.

  5. Damage control mechanisms in articular cartilage: the role of the insulin-like growth factor I axis.

    PubMed

    Martin, J A; Scherb, M B; Lembke, L A; Buckwalter, J A

    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

  6. Mechanical properties and structure-function relationships in articular cartilage repaired using IGF-I gene-enhanced chondrocytes.

    PubMed

    Griffin, Darvin J; Ortved, Kyla F; Nixon, Alan J; Bonassar, Lawrence J

    2016-01-01

    Several studies have demonstrated the benefits of IGF-I gene therapy in enhancing the histologic and biochemical content of cartilage repaired by chondrocyte transplantation. However, there is little to no data on the mechanical performance of IGF-I augmented cartilage grafts. This study evaluated the compressive properties of full-thickness chondral defects in the equine femur repaired with and without IGF-I gene therapy. Animals were randomly assigned to one of three study cohorts based on chondrocyte treatment provided in each defect: (i) IGF-I gene delivered by recombinant adeno-associated virus (rAAV)-5; (ii) AAV-5 delivering GFP as a reporter; (iii) naïve cells without virus. In each case, the opposite limb was implanted with a fibrin carrier without cells. Samples were prepared for confined compression testing to measure the aggregate modulus and hydraulic permeability. All treatment groups, regardless of cell content or transduction, had mechanical properties inferior to native cartilage. Overexpression of IGF-I increased modulus and lowered permeability relative to other treatments. Investigation of structure-property relationships revealed that Ha and k were linearly correlated with GAG content but logarithmically correlated with collagen content. This provides evidence that IGF-I gene therapy can improve healing of articular cartilage and can greatly increase the mechanical properties of repaired grafts.

  7. The matrix components of the epiphyseal growth plate and articular cartilages from dogs treated with ammonium tetrathiomolybdate, a copper antagonist.

    PubMed

    Read, R; Sutherland, J; Ghosh, P

    1986-12-01

    As part of a project to study the effect of copper deficiency (CD) on bone development in young dogs, the composition and metabolism of proteoglycans (PGs) and extractability of collagens in the epiphyseal growth plate cartilage (EGPC) and articular cartilages (AC) were investigated. Copper deficiency was induced by feeding ammonium tetrathiomolybdate (TTM) a copper antagonist. The collagen of cartilages from TTM-treated animals was significantly more soluble in 0.5 saline than control tissues. While no distinction between TTM-treated and control cartilages was evident in terms of PG content or extractability under associative (0.5 M-GuHCl) or dissociative (4.0 M-GuHCl) conditions, the sedimentation behaviour of the PG aggregates following CsCl density gradient ultracentrifugation suggested less polydispersity of PGs in preparations from the TTM-treated animals. Moreover, analysis of the PG monomers from EGPC of TTM animals showed galactosamine/glucosamine ratios higher than control preparations, suggesting a reduced keratan sulphate content in these preparations. Organ culture of EGPC showed a significant reduction in the incorporation of 35S into PGs and of 3H-thymidine into DNA in the tissues of TTM-treated animals relative to controls. From these findings we deduce that the catabolism of PGs and the extent of collagen cross-linking in EGPC of TTM-treated animals may be reduced relative to age-matched control tissues.

  8. Monitoring of the degradation in the rat's articular cartilage inducing osteoarthritis using common-path Fourier-domain optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Shin, D. H.; Park, S. H.; Kim, B. Y.; Lee, M. Y.; Baik, H. K.; Seo, J. H.; Kang, J. U.; Song, C. G.

    2013-03-01

    The objective of this experiment is to evaluate the utility and limitations of optical coherence tomography (OCT) for real-time, high-resolution structural analysis. We monitored the degradation of the rat's articular cartilage inducing osteoarthritis (OA) and the change of the rat's articular cartilage recovery by treatment medication, using our developed common-path Fourier-domain (CP-FD) OCT. Also, we have done a comparative analysis the rat's articular cartilage and OA grade. To observe the progression of OA, we induced OA by injecting the monosodium iodoacetate (MIA) into the right knee joint. After the injection of MIA, we sacrificed the rats at intervals of 3 days and obtained OCT and histological images. OCT and histological images showed the OA progress of similar pattern. These results illustrated the potential for non-invasive diagnosis about the grade of OA using CP-FD OCT.

  9. Expression of hypoxia-inducible factor-1α in synovial fluid and articular cartilage is associated with disease severity in knee osteoarthritis

    PubMed Central

    Qing, Liming; Lei, Pengfei; Liu, Hao; Xie, Jie; Wang, Long; Wen, Ting; Hu, Yihe

    2017-01-01

    The aim of the present study was to examine hypoxia-inducible factor 1α (HIF-1α) levels in the synovial fluid and articular cartilage of patients with primary knee osteoarthritis (OA) and to investigate their association with the severity of disease. A total of 36 patients with knee OA and ten healthy controls were enrolled. Anteroposterior knee radiographs and/or Mankin scores were assessed to determine the disease severity of the affected knee. Radiographic grading of OA in the knee was performed according to Kellgren-Lawrence criteria. HIF-1α levels in synovial fluid were measured using enzyme-linked immunosorbent assay, whereas HIF-1α levels in articular cartilage were assessed with immunohistochemical methods. Compared with healthy controls, OA patients exhibited an increased HIF-1α concentration in synovial fluid (218.17±25.12 vs. 156.66±7.74 pg/ml; P<0.001) and articular cartilage (P<0.05). Furthermore, synovial fluid HIF-1α levels demonstrated a positive correlation with articular cartilage HIF-1α levels (Pearson's P=0.815; P<0.001). Subsequent analysis showed that synovial fluid HIF-1α levels were significantly correlated with the severity of disease (Spearman's ρ=0.933; P<0.001). Furthermore, articular cartilage levels of HIF-1α also correlated with disease severity (Spearman's ρ=−0.967; P<0.001). The findings of the present study suggested that HIF-1α in synovial fluid and articular cartilage is associated with progressive joint damage and is likely to be a useful biomarker for determining disease severity and progression in knee OA. PMID:28123469

  10. Histochemical and functional improvement of adipose-derived stem cell-based tissue-engineered cartilage by hyperbaric oxygen/air treatment in a rabbit articular defect model.

    PubMed

    Dai, Niann-Tzyy; Fan, Gang-Yi; Liou, Nien-Hsien; Wang, Yi-Wen; Fu, Keng-Yen; Ma, Kuo-Hsing; Liu, Jiang-Chuan; Chang, Shun-Cheng; Huang, Kun-Lun; Dai, Lien-Guo; Chen, Shyi-Gen; Chen, Tim-Mo

    2015-05-01

    Cartilage is exposed to compression forces during joint loading. Therefore, exogenous stimuli are frequently used in cartilage tissue engineering strategies to enhance chondrocyte differentiation and extracellular matrix (ECM) secretion. In this study, human adipose-derived stem cells were seeded on a gelatin/polycaprolactone scaffold to evaluate the histochemical and functional improvement of tissue-engineered cartilage after hyperbaric oxygen/air treatment in a rabbit articular defect model. Behavior tests showed beneficial effects on weight-bearing and rear leg-supporting capacities after treatment of tissue-engineered cartilage with 2.5 ATA oxygen or air. Moreover, positron emission tomography images and immunohistochemistry staining demonstrated hydroxyapatite formation and increased ECM synthesis, respectively, at the tissue-engineered cartilage graft site after high pressure oxygen/air treatment. Based on these results, we concluded that hyperbaric oxygen and air treatment can improve the quality of tissue-engineered cartilage in vivo by increasing the synthesis of ECM.

  11. Knee Cartilage Thickness, T1ρ and T2 Relaxation Time Are Related to Articular Cartilage Loading in Healthy Adults

    PubMed Central

    Van Rossom, Sam; Smith, Colin Robert; Zevenbergen, Lianne; Thelen, Darryl Gerard; Vanwanseele, Benedicte; Van Assche, Dieter; Jonkers, Ilse

    2017-01-01

    Cartilage is responsive to the loading imposed during cyclic routine activities. However, the local relation between cartilage in terms of thickness distribution and biochemical composition and the local contact pressure during walking has not been established. The objective of this study was to evaluate the relation between cartilage thickness, proteoglycan and collagen concentration in the knee joint and knee loading in terms of contact forces and pressure during walking. 3D gait analysis and MRI (3D-FSE, T1ρ relaxation time and T2 relaxation time sequence) of fifteen healthy subjects were acquired. Experimental gait data was processed using musculoskeletal modeling to calculate the contact forces, impulses and pressure distribution in the tibiofemoral joint. Correlates to local cartilage thickness and mean T1ρ and T2 relaxation times of the weight-bearing area of the femoral condyles were examined. Local thickness was significantly correlated with local pressure: medial thickness was correlated with medial condyle contact pressure and contact force, and lateral condyle thickness was correlated with lateral condyle contact pressure and contact force during stance. Furthermore, average T1ρ and T2 relaxation time correlated significantly with the peak contact forces and impulses. Increased T1ρ relaxation time correlated with increased shear loading, decreased T1ρ and T2 relaxation time correlated with increased compressive forces and pressures. Thicker cartilage was correlated with higher condylar loading during walking, suggesting that cartilage thickness is increased in those areas experiencing higher loading during a cyclic activity such as gait. Furthermore, the proteoglycan and collagen concentration and orientation derived from T1ρ and T2 relaxation measures were related to loading. PMID:28076431

  12. Repair of articular cartilage defects with tissue-engineered osteochondral composites in pigs.

    PubMed

    Cui, Weiding; Wang, Qing; Chen, Gang; Zhou, Shixiang; Chang, Qing; Zuo, Qiang; Ren, Kewei; Fan, Weimin

    2011-04-01

    To compare the results of repair of knee cartilage defects with tissue-engineered osteochondral composites and tissue-engineered cartilage in pigs. Autologous chondrocytes and osteoblasts were seeded on scaffolds of polylactic-co-glycolic acid (PLGA) and tricalcium phosphate (TCP) to generate tissue-engineered cartilage and tissue-engineered bone, respectively. The tissue-engineered osteochondral composite was formed by a chondrocyte-PLGA construct sutured to an osteoblast-TCP construct with an absorbable suture. Cartilage defects were surgically created at the weightbearing surface of the bilateral femoral medial condyles of 12 mini-pigs. Thus, 24 defects in 12 pigs were randomly assigned to three treatment groups: tissue-engineered osteochondral composite group, tissue-engineered cartilage group, and blank control group. Six months after surgery, the regenerated cartilage was scored macroscopically and histologically. The compressive properties and glycosaminoglycan (GAG) content of the cartilage were also assessed. The gross grading scale indicated that the mean scores of the tissue-engineered osteochondral composite group were significantly higher than those of the tissue-engineered cartilage group. According to the International Cartilage Repair Society (ICRS) Visual Histological Assessment Scale, the scores of the osteochondral composite group were significantly better than those of the tissue-engineered cartilage group and blank control group. Assessment of compressive properties and GAG content showed better repair results in the osteochondral composite group than those of the tissue-engineered cartilage group. Using tissue-engineered osteochondral composites to repair cartilage defects was better than that of tissue-engineered cartilage.

  13. Use of micro-computed tomography to evaluate the effects of exercise on preventing the degeneration of articular cartilage in tail-suspended rats

    NASA Astrophysics Data System (ADS)

    Luan, Hui-Qin; Sun, Lian-Wen; Huang, Yun-Fei; Wu, Xin-tong; Niu, Haijun; Liu, Hong; Fan, Yu-Bo

    2015-07-01

    Space flight has been shown to induce bone loss and muscle atrophy, which could initiate the degeneration of articular cartilage. Countermeasures to prevent bone loss and muscle atrophy have been explored, but few spaceflight or ground-based studies have focused on the effects on cartilage degeneration. In this study, we investigated the effects of exercise on articular cartilage deterioration in tail-suspended rats. Thirty-two female Sprague-Dawley rats were randomly divided into four groups (n = 8 in each): tail suspension (TS), tail suspension plus passive motion (TSP), tail suspension plus active exercise (TSA), and control (CON) groups. In the TS, TSP, and TSA groups, the rat hindlimbs were unloaded for 21 days by tail suspension. Next, the cartilage thickness and volume, and the attenuation coefficient of the distal femur were evaluated by micro-computed tomography (μCT). Histological analysis was used to assess the surface integrity of the cartilage, cartilage thickness, and chondrocytes. The results showed that: (1) the cartilage thickness on the distal femur was significantly lower in the TS and TSP groups compared with the CON and TSA groups; (2) the cartilage volume in the TS group was significantly lower compared with the CON, TSA, and TSP groups; and (3) histomorphology showed that the chondrocytes formed clusters where the degree of matrix staining was lower in the TS and TSP groups. There were no significant differences between any of these parameters in the CON and TSA groups. The cartilage thickness measurements obtained by μCT and histomorphology correlated well. In general, tail suspension could induce articular cartilage degeneration, but active exercise was effective in preventing this degeneration in tail-suspended rats.

  14. Postnatal administration of 2-oxoglutaric acid improves articular and growth plate cartilages and bone tissue morphology in pigs prenatally treated with dexamethasone.

    PubMed

    Tomaszewska, E; Dobrowolski, P; Wydrych, J

    2012-10-01

    The potential effects of prenatal administration of dexamethasone (DEX) and postnatal treatment with 2-oxoglutaric acid (2-Ox) on postnatal development of connective tissue of farm animals were not examined experimentally. The aim of this study was to establish changes in morphological parameters of bone and articular and growth plate cartilages damaged by the prenatal action of DEX in piglets supplemented with 2-Ox. The 3 mg of DEX was administered by intramuscular route every second day from day 70 of pregnancy to parturition and then piglets were supplemented with 2-Ox during 35 days of postnatal life (0.4 g/kg body weight). The mechanical properties, BMD and BMC of bones, and histomorphometry of articular and growth plate cartilages were determined. Maternal treatment with DEX decreased the weight by 48%, BMD by 50% and BMC by 61% of the tibia in male piglets while such action of DEX in female piglets was not observed. DEX led to thinning of articular and growth plate cartilages and trabeculae thickness and reduced the serum GH concentration in male piglets. The administration of 2-Ox prevented the reduction of trabeculae thickness, the width of articular and growth plate cartilages in male piglets connected with higher growth hormone concentration compared with non-supplemented male piglets. The result showed that the presence of 2-Ox in the diet had a positive effect on the development of connective tissue in pigs during suckling and induced a complete recovery from bone and cartilage damage caused by prenatal DEX action.

  15. Topographical variations in the polarization sensitivity of articular cartilage as determined by polarization-sensitive optical coherence tomography and polarized light microscopy.

    PubMed

    Xie, Tuqiang; Xia, Yang; Guo, Shuguang; Hoover, Patrick; Chen, Zhongping; Peavy, George M

    2008-01-01

    To understand the influence of topographical variations in collagen fibril orientation of articular cartilage on optical phase images of polarization-sensitive optical coherence tomography (PS-OCT), we use polarized light microscopy (PLM) to quantify the orientation and phase retardation of the collagen architecture in cartilage at the same locations imaged by PS-OCT. The PS-OCT experiments demonstrate that articular cartilage has normal variations in polarization sensitivity at different locations over an intact bovine tibial plateau. Articular cartilage is not polarization sensitive along the vertical axis on the medial edge and central areas of the joint surface, but becomes polarization sensitive on the lateral edge of the tibia. This difference in optical phase retardation, as demonstrated by PS-OCT, is verified by PLM to be caused by differences in collagen fibril orientation at different locations of the tibial plateau. This study demonstrates that normal topographical variations in the collagen architecture of articular cartilage within a joint have a profound influence on the optical phase retardation detected by PS-OCT imaging, and therefore must be understood and mapped for specific joints before PS-OCT imaging can be used for the evaluation of the health status of individual joint surfaces.

  16. Alterations in mechanical behaviour of articular cartilage due to changes in depth varying material properties--a nonhomogeneous poroelastic model study.

    PubMed

    Li, L P; Shirazi-Adl, A; Buschmann, M D

    2002-02-01

    The depth dependence of the material properties is present in normal adult cartilage and is believed to have significant implications in its normal mechanical function. Cartilage pathology may alter the depth dependence, e.g. a reduced depth dependence of the fibril stiffness has been observed in osteoarthritic cartilage. The objective of the present study is to investigate the alterations in the mechanical response of articular cartilage when the depth dependence of the material properties is varied to simulate healthy and pathological situations. This study is made possible by a recently developed nonhomogeneous poroelastic model. Depth variations of the strains and stresses for individual material phases (collagen, proteoglycan and fluid) are obtained for cartilage disks in unconfined compression using the finite element method. The mean nominal axial strain considered is up to 15%, while the axial strain at the articular surface can reach 33%. This paper demonstrates how the mechanical behaviours of cartilage are affected by individual depth dependent cartilage properties, while such observations are not fully available in experimental investigations. This study suggests the possibility of diagnosing cartilage health by analysing its mechanical behaviours.

  17. Simulation of high tensile Poisson's ratios of articular cartilage with a finite element fibril-reinforced hyperelastic model.

    PubMed

    García, José Jaime

    2008-06-01

    Analyses with a finite element fibril-reinforced hyperelastic model were undertaken in this study to simulate high tensile Poisson's ratios that have been consistently documented in experimental studies of articular cartilage. The solid phase was represented by an isotropic matrix reinforced with four sets of fibrils, two of them aligned in orthogonal directions and two oblique fibrils in a symmetric configuration respect to the orthogonal axes. Two distinct hyperelastic functions were used to represent the matrix and the fibrils. Results of the analyses showed that only by considering non-orthogonal fibrils was it possible to represent Poisson's ratios higher than one. Constrains in the grips and finite deformations played a minor role in the calculated Poisson's ratio. This study also showed that the model with oblique fibrils at 45 degrees was able to represent significant differences in Poisson's ratios near 1 documented in experimental studies. However, even considering constrains in the grips, this model was not capable to simulate Poisson's ratios near 2 that have been reported in other studies. The study also confirmed that only with a high relation between the stiffness of the fibers and that of the matrix was it possible to obtain high Poisson's ratios for the tissue. Results suggest that analytical models with a finite number of fibrils are appropriate to represent main mechanical effects of articular cartilage.

  18. Raman Spectroscopy Reveals New Insights into the Zonal Organization of Native and Tissue-Engineered Articular Cartilage

    PubMed Central

    2016-01-01

    Tissue architecture is intimately linked with its functions, and loss of tissue organization is often associated with pathologies. The intricate depth-dependent extracellular matrix (ECM) arrangement in articular cartilage is critical to its biomechanical functions. In this study, we developed a Raman spectroscopic imaging approach to gain new insight into the depth-dependent arrangement of native and tissue-engineered articular cartilage using bovine tissues and cells. Our results revealed previously unreported tissue complexity into at least six zones above the tidemark based on a principal component analysis and k-means clustering analysis of the distribution and orientation of the main ECM components. Correlation of nanoindentation and Raman spectroscopic data suggested that the biomechanics across the tissue depth are influenced by ECM microstructure rather than composition. Further, Raman spectroscopy together with multivariate analysis revealed changes in the collagen, glycosaminoglycan, and water distributions in tissue-engineered constructs over time. These changes were assessed using simple metrics that promise to instruct efforts toward the regeneration of a broad range of tissues with native zonal complexity and functional performance. PMID:28058277

  19. Manifold learning for automatically predicting articular cartilage morphology in the knee with data from the osteoarthritis initiative (OAI)

    NASA Astrophysics Data System (ADS)

    Donoghue, C.; Rao, A.; Bull, A. M. J.; Rueckert, D.

    2011-03-01

    Osteoarthritis (OA) is a degenerative, debilitating disease with a large socio-economic impact. This study looks to manifold learning as an automatic approach to harness the plethora of data provided by the Osteoarthritis Initiative (OAI). We construct several Laplacian Eigenmap embeddings of articular cartilage appearance from MR images of the knee using multiple MR sequences. A region of interest (ROI) defined as the weight bearing medial femur is automatically located in all images through non-rigid registration. A pairwise intensity based similarity measure is computed between all images, resulting in a fully connected graph, where each vertex represents an image and the weight of edges is the similarity measure. Spectral analysis is then applied to these pairwise similarities, which acts to reduce the dimensionality non-linearly and embeds these images in a manifold representation. In the manifold space, images that are close to each other are considered to be more "similar" than those far away. In the experiment presented here we use manifold learning to automatically predict the morphological changes in the articular cartilage by using the co-ordinates of the images in the manifold as independent variables for multiple linear regression. In the study presented here five manifolds are generated from five sequences of 390 distinct knees. We find statistically significant correlations (up to R2 = 0.75), between our predictors and the results presented in the literature.

  20. 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

  1. Solute Transport of Negatively Charged Contrast Agents Across Articular Surface of Injured Cartilage.

    PubMed

    Kokkonen, H T; Chin, H C; Töyräs, J; Jurvelin, J S; Quinn, T M

    2017-04-01

    Solute transport through the extracellular matrix (ECM) is crucial to chondrocyte metabolism. Cartilage injury affects solute transport in cartilage due to alterations in ECM structure and solute-matrix interactions. Therefore, cartilage injury may be detected by using contrast agent-based clinical imaging. In the present study, effects of mechanical injury on transport of negatively charged contrast agents in cartilage were characterized. Using cartilage plugs injured by mechanical compression protocol, effective partition coefficients and diffusion fluxes of iodine- and gadolinium-based contrast agents were measured using high resolution microCT imaging. For all contrast agents studied, effective diffusion fluxes increased significantly, particularly at early times during the diffusion process (38 and 33% increase after 4 min, P < 0.05 for iodine and Gd-DTPA; and 76% increase after 10 min for diatrizoate, P < 0.05). Effective partition coefficients were unaffected in mechanically injured cartilage. Mechanical injury reduced PG content and collagen integrity in cartilage superficial zone. This study suggests that alterations in contrast agent diffusion flux, a non-equilibrium transport parameter, provides a more sensitive indicator for assessment of cartilage matrix integrity than partition coefficient and the equilibrium distribution of solute. These findings may help in developing clinical methods of contrast agent-based imaging to detect cartilage injury.

  2. [Microdurimetric and biochemical study of human articular cartilage. Comparison of different joints].

    PubMed

    Vignon, E; Arlot, M; Hartman, D; Noyer, D

    1980-12-01

    The micro-hardness and the density of fixed negative charges in cartilage of the shoulders, hips and knees of 6 subjects were studied. These two parameters were narrowly correlated. The resistance and proteoglycan concentration of the cartilage of the femoral head were greater than those of the knee and of the shoulder. They did not vary on each side. There is a significant correlation between the hardness of the cartilage of the femoral head and of the external femoral condyle. The histologically normal cartilage of the femoral head in arthrosis is at the lower limit of control values for hardness.

  3. Intra-articular injection of tenoxicam in rats: assessment of the local effects on the articular cartilage and synovium.

    PubMed

    Ozyuvaci, H; Bilgic, B; Ozyuvaci, E; Altan, A; Altug, T; Karaca, C

    2004-01-01

    This study investigated the possible local adverse effects of intra-articular administration of tenoxicam in the rat knee joint. A total of 50 rats were given 0.25 ml of a standard preparation of tenoxicam by injection into the right knee joint and 0.25 ml of 0.9% saline solution by injection into the left knee joint as a control. Groups of 10 rats were killed 24 h, 48 h, 7 days, 14 days and 21 days after tenoxicam administration. Two rats were sham operated; one was killed on the first day and the other on the second day after this procedure. All the joints were prepared and sectioned for histological examination. Tissue loss and oedema were observed in the specimens obtained 24 h and 48 h after treatment with tenoxicam. No pathological changes were observed in the 7-day, 14-day and 21-day specimens, or in the control joints. Caution should be exercised when using intra-articular tenoxicam for post-operative analgesia.

  4. Experimental issues in the measurement of multi-component relaxation times in articular cartilage by microscopic MRI

    NASA Astrophysics Data System (ADS)

    Wang, Nian; Xia, Yang

    2013-10-01

    A number of experimental issues in the measurement of multi-component T2 and T1ρ relaxations in native and enzymatically digested articular cartilage were investigated by microscopic MRI (μMRI). The issues included the bath solutions (physiological saline and phosphate buffered saline (PBS)), the imaging resolution (35-140 μm), the specimen orientations (0° and 55°), and the strength of spin-lock frequencies (0.5-2 kHz) in the T1ρ experiments. In addition to cartilage, the samples of agar gel and doped water solution were also used in the investigation. Two imaging sequences were used: CPMG-SE and MSME. All raw data were analyzed by the non-negative least square (NNLS) method. The MSME sequence was shown to result in the observation of multi-component T2, even in the gel and liquid samples, demonstrating the artificial uncleanness of this sequence in the multi-component measurements. The soaking of cartilage in PBS reduced the observable T2 components to one at both 0° and 55°, suggesting the effect of phosphate ions on proton exchange between different pools of water molecules. The cartilage orientation with respect to the external magnetic field and the spin-lock strengths in the T1ρ experiment both affected the quantification of the multi-component relaxation. The transitions between a mono-component and multi-components in cartilage under various experimental conditions call for the extra caution in interpreting the relaxation results.

  5. Experimental issues in the measurement of multi-component relaxation times in articular cartilage by microscopic MRI.

    PubMed

    Wang, Nian; Xia, Yang

    2013-10-01

    A number of experimental issues in the measurement of multi-component T2 and T1ρ relaxations in native and enzymatically digested articular cartilage were investigated by microscopic MRI (μMRI). The issues included the bath solutions (physiological saline and phosphate buffered saline (PBS)), the imaging resolution (35-140 μm), the specimen orientations (0° and 55°), and the strength of spin-lock frequencies (0.5-2 kHz) in the T1ρ experiments. In addition to cartilage, the samples of agar gel and doped water solution were also used in the investigation. Two imaging sequences were used: CPMG-SE and MSME. All raw data were analyzed by the non-negative least square (NNLS) method. The MSME sequence was shown to result in the observation of multi-component T2, even in the gel and liquid samples, demonstrating the artificial uncleanness of this sequence in the multi-component measurements. The soaking of cartilage in PBS reduced the observable T2 components to one at both 0° and 55°, suggesting the effect of phosphate ions on proton exchange between different pools of water molecules. The cartilage orientation with respect to the external magnetic field and the spin-lock strengths in the T1ρ experiment both affected the quantification of the multi-component relaxation. The transitions between a mono-component and multi-components in cartilage under various experimental conditions call for the extra caution in interpreting the relaxation results.

  6. Altered swelling and ion fluxes in articular cartilage as a biomarker in osteoarthritis and joint immobilization: a computational analysis

    PubMed Central

    Manzano, Sara; Manzano, Raquel; Doblaré, Manuel; Doweidar, Mohamed Hamdy

    2015-01-01

    In healthy cartilage, mechano-electrochemical phenomena act together to maintain tissue homeostasis. Osteoarthritis (OA) and degenerative diseases disrupt this biological equilibrium by causing structural deterioration and subsequent dysfunction of the tissue. Swelling and ion flux alteration as well as abnormal ion distribution are proposed as primary indicators of tissue degradation. In this paper, we present an extension of a previous three-dimensional computational model of the cartilage behaviour developed by the authors to simulate the contribution of the main tissue components in its behaviour. The model considers the mechano-electrochemical events as concurrent phenomena in a three-dimensional environment. This model has been extended here to include the effect of repulsion of negative charges attached to proteoglycans. Moreover, we have studied the fluctuation of these charges owning to proteoglycan variations in healthy and pathological articular cartilage. In this sense, standard patterns of healthy and degraded tissue behaviour can be obtained which could be a helpful diagnostic tool. By introducing measured properties of unhealthy cartilage into the computational model, the severity of tissue degeneration can be predicted avoiding complex tissue extraction and subsequent in vitro analysis. In this work, the model has been applied to monitor and analyse cartilage behaviour at different stages of OA and in both short (four, six and eight weeks) and long-term (11 weeks) fully immobilized joints. Simulation results showed marked differences in the corresponding swelling phenomena, in outgoing cation fluxes and in cation distributions. Furthermore, long-term immobilized patients display similar swelling as well as fluxes and distribution of cations to patients in the early stages of OA, thus, preventive treatments are highly recommended to avoid tissue deterioration. PMID:25392400

  7. Cartilage Viability and Catabolism in the Intact Porcine Knee Following Transarticular Impact Loading with and without Articular Fracture

    PubMed Central

    Backus, Jonathon D.; Furman, Bridgette D.; Swimmer, Troy; Kent, Collin L.; McNulty, Amy L.; DeFrate, Louis E.; Guilak, Farshid; Olson, Steven A.

    2011-01-01

    Posttraumatic arthritis commonly develops following articular fracture. The objective of this study was to develop a closed joint model of transarticular impact with and without creation of an articular fracture that maintains the physiologic environment during loading. Fresh intact porcine knees were preloaded and impacted at 294 J via a drop track. Osteochondral cores were obtained from the medial and lateral aspects of the femoral condyles and tibial plateau. Chondrocyte viability was assessed at days 0, 3 and 5 post-impact in sham, impacted nonfractured, and impacted fractured joints. Total matrix metalloproteinase (MMP) activity, aggrecanase (ADAMTS-4) activity, and sulfated glycosaminoglycan (S-GAG) release was measured in culture media from days 3 and 5 post-trauma. No differences were observed in chondrocyte viability of impacted nonfractured joints (95.9±6.9%) when compared to sham joints (93.8±7.7%). In impacted fractured joints, viability of the fractured edge was 40.5±27.6% and significantly lower than all other sites, including cartilage adjacent to the fractured edge (p<0.001). MMP and aggrecanase activity and S-GAG release were significantly increased in specimens from the fractured edge. This study showed that joint impact resulting in articular fracture significantly decreased chondrocyte viability, increased production of MMPs and aggrecanases, and enhanced S-GAG release, whereas the same level of impact without fracture did not cause such changes. PMID:21337389

  8. Influence of Knee Immobilization on Chondrocyte Apoptosis and Histological Features of the Anterior Cruciate Ligament Insertion and Articular Cartilage in Rabbits

    PubMed Central

    Mutsuzaki, Hirotaka; Nakajima, Hiromi; Wadano, Yasuyoshi; Furuhata, Syogo; Sakane, Masataka

    2017-01-01

    This study examined the influence of immobilization on chondrocyte apoptosis and histological features of the anterior cruciate ligament (ACL) insertion and knee articular cartilage in rabbits. Forty-eight male Japanese white rabbits were assigned to an immobilization (n = 24) or sham (n = 24) group. Rabbits in the immobilization group underwent complete unilateral surgical knee immobilization and rabbits in the sham group underwent a sham surgery. The average thickness of the glycosaminoglycan (GAG) stained red area by safranin O staining, the chondrocyte apoptosis rate and the chondrocyte proliferation rate in the cartilage layer in the ACL insertion and the articular cartilage of the medial tibial condyle were measured at one, two, four and eight weeks in six animals from each group. In the ACL insertion, the chondrocyte apoptosis rate was higher in the immobilization group than in the sham group at two and eight weeks after surgery (p < 0.05). The chondrocyte proliferation rate gradually decreased from two weeks to eight weeks in the immobilization group. The GAG layer was thinner in the immobilization group than in the sham group at two, four and eight weeks after surgery (p < 0.05). In the articular cartilage, the chondrocyte apoptosis rate in the immobilization group was higher than in the sham group at four and eight weeks after surgery (p < 0.05). The GAG layer was significantly thinner in the immobilization group than that in the sham group at four and eight weeks after surgery (p < 0.05). Knee immobilization significantly increased chondrocyte apoptosis at two and eight weeks after surgery in the ACL insertion and at four and eight weeks after surgery in the articular cartilage of the medial tibial condyle, and decreased GAG layer thickness from two to eight weeks after surgery in the ACL insertion and from four to eight weeks after surgery in the articular cartilage. PMID:28134763

  9. Correlation between plasma, synovial fluid and articular cartilage Interleukin-18 with radiographic severity in 33 patients with osteoarthritis of the knee.

    PubMed

    Wang, Youhua; Xu, Dawei; Long, Long; Deng, Xiaolong; Tao, Ran; Huang, Guicheng

    2014-08-01

    Osteoarthritis (OA) is a complex disease characterized by cartilage degeneration, secondary synovial membrane inflammation and subchondral bone changes. In recent years, many studies have confirmed that interleukin-18 (IL-18) is involved in the inflammatory process of inflammatory joint diseases. In the present study, we investigated IL-18 levels in plasma, synovial fluid and articular cartilage of patients with primary knee OA (n = 33) to analyze their relationship with radiographic severity. Compared to healthy controls (n = 15), OA patients had higher plasma and synovial fluid IL-18 concentrations(45.8 ± 22.1 vs. 23.7 ± 13.6 pg/ml, P<0.001 and 75.2 ± 40.1 vs. 28.3 ± 11.6 pg/ml, P<0.001) as measured by enzyme-linked immunosorbent assay. Also,the percentage of immunofluorescent IL-18 positive cells in articular cartilage was significantly increased in OA compared to controls (46.5 ± 10.3 vs. 2.9 ± 1.7, P<0.001). Moreover, plasma, synovial fluid and articular cartilage IL-18 significantly positively correlated with radiographic severity, respectively (r = 0.663, P<0.001, r = 0.56, P = 0.001 and r = 0.884, P<0.001). Subsequent analysis revealed that plasma, synovial fluid and articular cartilage IL-18 levels positively correlated with each other (r = 0.632, P<0.001, r = 0.489, P = 0.004 and r = 0.620, P<0.001). These data suggested that plasma, synovial fluid and articular cartilage IL-18 levels were significantly increased in OA patients, and these elevated levels were positively correlated with radiographic severity. Accordingly, our study supports the role of IL-18 in the pathophysiology of OA.

  10. Nanomechanics of Engineered Articular Cartilage: Synergistic Influences of Transforming Growth Factor-β3 and Oscillating Pressure

    PubMed Central

    Van Wie, Bernard J.

    2016-01-01

    Articular cartilage (AC), tissue with the lowest volumetric cellular density, is not supplied with blood and nerve resulting in limited ability for self-repair upon injury. Because there is no treatment capable of fully restoring damaged AC, tissue engineering is being investigated. The emphasis of this field is to engineer functional tissues in vitro in bioreactors capable of mimicking in vivo environments required for appropriate cellular growth and differentiation. In a step towards engineering AC, human adipose-derived stem cells were differentiated in a unique centrifugal bioreactor under oscillating hydrostatic pressure (OHP) and supply of transforming growth factor beta 3 (TGF-β3) that mimic in vivo environments. Static micromass and pellet cultures were used as controls. Since withstanding and absorbing loads are among the main functions of an AC, mechanical properties of the engineered AC tissues were assayed using atomic force microscopy (AFM) under a controlled indentation depth of 100 nm. Young's moduli of elasticity were quantified by modeling AFM force-indentation data using the Hertz model of contact mechanics. We found exposure to OHP causes cartilage constructs to have 45-fold higher Young's moduli compared to static cultures. Addition of TGF-β3 further increases Young's moduli in bioreactor samples by 1.9-fold bringing it within 70.6% of the values estimated for native cartilage. Our results imply that OHP and TGF-β3 act synergistically to improve the mechanics of engineered tissues. PMID:27455774

  11. In Vitro Expression of the Extracellular Matrix Components Aggrecan, Collagen Types I and II by Articular Cartilage-Derived Chondrocytes.

    PubMed

    Schneevoigt, J; Fabian, C; Leovsky, C; Seeger, J; Bahramsoltani, M

    2017-02-01

    The extracellular matrix (ECM) of hyaline cartilage is perfectly suited to transmit articular pressure load to the subchondral bone. Pressure is transferred by a high amount of aggrecan-based proteoglycans and collagen type II fibres in particular. After any injury, the hyaline cartilage is replaced by fibrocartilage, which is low in proteoglycans and contains collagen type I predominantly. Until now, long-term results of therapeutic procedures including cell-based therapies like autologous chondrocyte transplantation (ACT) lead to a replacement tissue meeting the composition of fibrocartilage. Therefore, it is of particular interest to discover how and to what extent isolation and in vitro cultivation of chondrocytes affect the cells and their expression of ECM components. Hyaline cartilage-derived chondrocytes were cultivated in vitro and observed microscopically over a time period of 35 days. The expression of collagen type I, collagen type II and aggrecan was analysed using RT-qPCR and Western blot at several days of cultivation. Chondrocytes presented a longitudinal shape for the entire cultivation period. While expression of collagen type I prevailed within the first days, only prolonged cultivation led to an increase in collagen type II and aggrecan expression. The results indicate that chondrocyte isolation and in vitro cultivation lead to a dedifferentiation at least to the stage of chondroprogenitor cells.

  12. Normal and shear interactions between hyaluronan-aggrecan complexes mimicking possible boundary lubricants in articular cartilage in synovial joints.

    PubMed

    Seror, Jasmine; Merkher, Yulia; Kampf, Nir; Collinson, Lisa; Day, Anthony J; Maroudas, Alice; Klein, Jacob

    2012-11-12

    Using a surface force balance, normal and shear interactions have been measured between two atomically smooth surfaces coated with hyaluronan (HA), and with HA/aggrecan (Agg) complexes stabilized by cartilage link protein (LP). Such HA/Agg/LP complexes are the most abundant mobile macromolecular species permeating articular cartilage in synovial joints and have been conjectured to be present as boundary lubricants at its surface. The aim of the present study is to gain insight into the extremely efficient lubrication when two cartilage surfaces slide past each other in healthy joints, and in particular to elucidate the possible role in this of the HA/Agg/LP complexes. Within the range of our parameters, our results reveal that the HA/Agg/LP macromolecular surface complexes are much better boundary lubricants than HA alone, likely because of the higher level of hydration, due to the higher charge density, of the HA/Agg/LP layers with respect to the HA alone. However, the friction coefficients (μ) associated with the mutual interactions and sliding of opposing HA/Agg/LP layers (μ ≈ 0.01 up to pressure P of ca. 12 atm, increasing sharply at higher P) suggest that such complexes by themselves cannot account for the remarkable boundary lubrication observed in mammalian joints (up to P > 50 atm).

  13. Biologic Treatments for Sports Injuries II Think Tank-Current Concepts, Future Research, and Barriers to Advancement, Part 3: Articular Cartilage.

    PubMed

    Zlotnicki, Jason P; Geeslin, Andrew G; Murray, Iain R; Petrigliano, Frank A; LaPrade, Robert F; Mann, Barton J; Musahl, Volker

    2016-04-01

    Focal chondral defects of the articular surface are a common occurrence in the field of orthopaedics. These isolated cartilage injuries, if not repaired surgically with restoration of articular congruency, may have a high rate of progression to posttraumatic osteoarthritis, resulting in significant morbidity and loss of function in the young, active patient. Both isolated and global joint disease are a difficult entity to treat in the clinical setting given the high amount of stress on weightbearing joints and the limited healing potential of native articular cartilage. Recently, clinical interest has focused on the use of biologically active compounds and surgical techniques to regenerate native cartilage to the articular surface, with the goal of restoring normal joint health and overall function. This article presents a review of the current biologic therapies, as discussed at the 2015 American Orthopaedic Society for Sports Medicine (AOSSM) Biologics Think Tank, that are used in the treatment of focal cartilage deficiencies. For each of these emerging therapies, the theories for application, the present clinical evidence, and specific areas for future research are explored, with focus on the barriers currently faced by clinicians in advancing the success of these therapies in the clinical setting.

  14. Transport of neutral solute across articular cartilage: the role of zonal diffusivities.

    PubMed

    Arbabi, V; Pouran, B; Weinans, H; Zadpoor, A A

    2015-07-01

    Transport of solutes through diffusion is an important metabolic mechanism for the avascular cartilage tissue. Three types of interconnected physical phenomena, namely mechanical, electrical, and chemical, are all involved in the physics of transport in cartilage. In this study, we use a carefully designed experimental-computational setup to separate the effects of mechanical and chemical factors from those of electrical charges. Axial diffusion of a neutral solute Iodixanol into cartilage was monitored using calibrated microcomputed tomography micro-CT images for up to 48 hr. A biphasic-solute computational model was fitted to the experimental data to determine the diffusion coefficients of cartilage. Cartilage was modeled either using one single diffusion coefficient (single-zone model) or using three diffusion coefficients corresponding to superficial, middle, and deep cartilage zones (multizone model). It was observed that the single-zone model cannot capture the entire concentration-time curve and under-predicts the near-equilibrium concentration values, whereas the multizone model could very well match the experimental data. The diffusion coefficient of the superficial zone was found to be at least one order of magnitude larger than that of the middle zone. Since neutral solutes were used, glycosaminoglycan (GAG) content cannot be the primary reason behind such large differences between the diffusion coefficients of the different cartilage zones. It is therefore concluded that other features of the different cartilage zones such as water content and the organization (orientation) of collagen fibers may be enough to cause large differences in diffusion coefficients through the cartilage thickness.

  15. Micro- and nanomechanical analysis of articular cartilage by indentation-type atomic force microscopy: validation with a gel-microfiber composite.

    PubMed

    Loparic, Marko; Wirz, Dieter; Daniels, A U; Raiteri, Roberto; Vanlandingham, Mark R; Guex, Geraldine; Martin, Ivan; Aebi, Ueli; Stolz, Martin

    2010-06-02

    As documented previously, articular cartilage exhibits a scale-dependent dynamic stiffness when probed by indentation-type atomic force microscopy (IT-AFM). In this study, a micrometer-size spherical tip revealed an unimodal stiffness distribution (which we refer to as microstiffness), whereas probing articular cartilage with a nanometer-size pyramidal tip resulted in a bimodal nanostiffness distribution. We concluded that indentation of the cartilage's soft proteoglycan (PG) gel gave rise to the lower nanostiffness peak, whereas deformation of its collagen fibrils yielded the higher nanostiffness peak. To test our hypothesis, we produced a gel-microfiber composite consisting of a chondroitin sulfate-containing agarose gel and a fibrillar poly(ethylene glycol)-terephthalate/poly(butylene)-terephthalate block copolymer. In striking analogy to articular cartilage, the microstiffness distribution of the synthetic composite was unimodal, whereas its nanostiffness exhibited a bimodal distribution. Also, similar to the case with cartilage, addition of the negatively charged chondroitin sulfate rendered the gel-microfiber composite's water content responsive to salt. When the ionic strength of the surrounding buffer solution increased from 0.15 to 2 M NaCl, the cartilage's microstiffness increased by 21%, whereas that of the synthetic biomaterial went up by 31%. When the nanostiffness was measured after the ionic strength was raised by the same amount, the cartilage's lower peak increased by 28%, whereas that of the synthetic biomaterial went up by 34%. Of interest, the higher peak values remained unchanged for both materials. Taken together, these results demonstrate that the nanoscale lower peak is a measure of the soft PG gel, and the nanoscale higher peak measures collagen fibril stiffness. In contrast, the micrometer-scale measurements fail to resolve separate stiffness values for the PG and collagen fibril moieties. Therefore, we propose to use nanostiffness as a

  16. Aggrecan turnover in human articular cartilage: use of aspartic acid racemization as a marker of molecular age.

    PubMed

    Maroudas, A; Bayliss, M T; Uchitel-Kaushansky, N; Schneiderman, R; Gilav, E

    1998-02-01

    Aggrecan is a key component of the cartilage matrix. During aging, many changes occur in its composition and structure; in particular, there is an increase in the proportion of lower molecular weight monomers and of the "free" binding region. An important question has been whether these changes represent alterations in biosynthesis or whether they are due to the accumulation with age of the partially degraded fragments of the originally synthesized large monomer. In the present work we have used an independent tool, viz., the extent of racemization of aspartic acid to study the molecular "age" of different buoyant density fractions of the aggrecan of human articular cartilage, as well as of isolated free binding region and link protein. By measuring the D/LAsp ratio of the different aggrecan species, we were able to establish directly the relative residence times of these molecules in the cartilage matrix and, in combination with compositional and structural analyses, to define their "history" and calculate some of the kinetics constants characterizing their turnover. The value of the turnover constant for the large monomer in fraction A1D1 is 0.206 per year, which corresponds to a half-life of 3.4 years, while the turnover constant for the free binding region is 0.027 per year, which corresponds to a half-life of 25 years. It is thus clear that the rate of formation and turnover of the large monomer is much more rapid than the final degradation of the free binding region fragments, which explains the accumulation of the latter in cartilage during aging.

  17. Integration of stem cell-derived exosomes with in situ hydrogel glue as a promising tissue patch for articular cartilage regeneration.

    PubMed

    Liu, Xiaolin; Yang, Yunlong; Li, Yan; Niu, Xin; Zhao, Bizeng; Wang, Yang; Bao, Chunyan; Xie, Zongping; Lin, Qiuning; Zhu, Linyong

    2017-03-16

    The regeneration of articular cartilage, which scarcely shows innate self-healing ability, is a great challenge in clinical treatment. Stem cell-derived exosomes (SC-Exos), an important type of extracellular nanovesicle, exhibit great potential for cartilage regeneration to replace stem cell-based therapy. Cartilage regeneration often takes a relatively long time and there is currently no effective administration method to durably retain exosomes at cartilage defect sites to effectively exert their reparative effect. Therefore, in this study, we exploited a photoinduced imine crosslinking hydrogel glue, which presents excellent operation ability, biocompatibility and most importantly, cartilage-integration, as an exosome scaffold to prepare an acellular tissue patch (EHG) for cartilage regeneration. It was found that EHG can retain SC-Exos and positively regulate both chondrocytes and hBMSCs in vitro. Furthermore, EHG can integrate with native cartilage matrix and promote cell deposition at cartilage defect sites, finally resulting in the promotion of cartilage defect repair. The EHG tissue patch therefore provides a novel, cell-free scaffold material for wound repair.

  18. Homeostatic Mechanisms in Articular Cartilage and Role of Inflammation in Osteoarthritis

    PubMed Central

    Houard, Xavier; Goldring, Mary B.; Berenbaum, Francis

    2014-01-01

    Osteoarthritis (OA) is a whole joint disease, in which thinning and disappearance of cartilage is a critical determinant in OA progression. The rupture of cartilage homeostasis whatever its cause: aging, genetic predisposition, trauma or metabolic disorder, induces profound phenotypic modifications of chondrocytes, which then promote the synthesis of a subset of factors that induce cartilage damage and target other joint tissues. Interestingly, among these factors are numerous components of the inflammatory pathways. Chondrocytes produce cytokines, chemokines, alarmins, prostanoids and adipokines and express numerous cell surface receptors for cytokines and chemokines, as well as toll-like receptors. These receptors activate intracellular signaling pathways involved in inflammatory and stress responses of chondrocytes in OA joints. This review focuses on mechanisms responsible for the maintenance of cartilage homeostasis and highlights the role of inflammatory processes in OA progression. PMID:24072604

  19. Repair of experimentally produced defects in rabbit articular cartilage by autologous chondrocyte transplantation

    SciTech Connect

    Grande, D.A.; Pitman, M.I.; Peterson, L.; Menche, D.; Klein, M.

    1989-01-01

    Using the knee joints of New Zealand White rabbits, a baseline study was made to determine the intrinsic capability of cartilage for healing defects that do not fracture the subchondral plate. A second experiment examined the effect of autologous chondrocytes grown in vitro on the healing rate of these defects. To determine whether any of the reconstituted cartilage resulted from the chondrocyte graft, a third experiment was conducted involving grafts with chondrocytes that had been labeled prior to grafting with a nuclear tracer. Results were evaluated using both qualitative and quantitative light microscopy. Macroscopic results from grafted specimens displayed a marked decrease in synovitis and other degenerative changes. In defects that had received transplants, a significant amount of cartilage was reconstituted (82%) compared to ungrafted controls (18%). Autoradiography on reconstituted cartilage showed that there were labeled cells incorporated into the repair matrix.

  20. Stem cells catalyze cartilage formation by neonatal articular chondrocytes in 3D biomimetic hydrogels

    NASA Astrophysics Data System (ADS)

    Lai, Janice H.; Kajiyama, Glen; Smith, Robert Lane; Maloney, William; Yang, Fan

    2013-12-01

    Cartilage loss is a leading cause of disability among adults and effective therapy remains elusive. Neonatal chondrocytes (NChons) are an attractive allogeneic cell source for cartilage repair, but their clinical translation has been hindered by scarce donor availability. Here we examine the potential for catalyzing cartilage tissue formation using a minimal number of NChons by co-culturing them with adipose-derived stem cells (ADSCs) in 3D hydrogels. Using three different co-culture models, we demonstrated that the effects of co-culture on cartilage tissue formation are dependent on the intercellular distance and cell distribution in 3D. Unexpectedly, increasing ADSC ratio in mixed co-culture led to increased synergy between NChons and ADSCs, and resulted in the formation of large neocartilage nodules. This work raises the potential of utilizing stem cells to catalyze tissue formation by neonatal chondrocytes via paracrine signaling, and highlights the importance of controlling cell distribution in 3D matrices to achieve optimal synergy.

  1. [Chondrocyte glycosyltransferases: new pharmacological targets for degenerative diseases of articular cartilage?].

    PubMed

    Magdalou, Jacques; Ouzzine, Mohamed; Netter, Patrick; Fournel-Gigleux, Sylvie

    2006-10-01

    Arthritis, osteoarthritis and other degenerative diseases characterized by cartilage deterioration are the most prevalent chronic human health disorders. Despite their major socioeconomic impact there is still no satisfactory treatment. Their frequency is increasing with the lengthening of life expectancy, creating a major public health challenge for coming years. It is important to diagnose such diseases at an early stage and to develop new effective therapies. We are attempting to develop new therapeutic approaches in this context, keeping in mind that cartilage is one of the few human tissues which is unable to regenerate. We intend to identify and characterize key proteins involved in the biosynthesis of cartilage matrix components. One innovative strategy consists of gene transfer, triggering overexpression of native or recombinant factors that can stimulate chondrocyte anabolic activity in order to promote cartilage repair The loss of matrix components, and especially glycosaminoglycans (GAG), is the earliest event in cartilage degeneration. We therefore looked at glycosyltransferases, and especially galactose beta1,3-glucuronosyltransferase-I (GlcAT-1), which catalyses one of the first steps in GAG biosynthesis. We found that any variation in GlcAT-I activity in chondrocytes or cartilage explants (overexpression, or repression with antisense RNA) affected the GAG content of cartilage. Interestingly, overexpression of this enzyme completely counteracted the GAG depletion produced by the proinflammatory cytokine interleukin 1-beta. The neosynthesized GAG was qualitatively identical to that present in the original cartilage matrix. These results are encouraging for therapeutic approaches based on gene transfer We also investigated the structure-function relationship of human recombinant GlcAT-I upon expression in the methyltrophic yeast Pichia pastoris. This allowed us to determine the molecular basis of the recognition of the donor and acceptor substrates of

  2. The acute effect of bipolar radiofrequency energy thermal chondroplasty on intrinsic biomechanical properties and thickness of chondromalacic human articular cartilage.

    PubMed

    Dutcheshen, Nicholas; Maerz, Tristan; Rabban, Patrick; Haut, Roger C; Button, Keith D; Baker, Kevin C; Guettler, Joseph

    2012-08-01

    Radio frequency energy (RFE) thermal chondroplasty has been a widely-utilized method of cartilage debridement in the past. Little is known regarding its effect on tissue mechanics. This study investigated the acute biomechanical effects of bipolar RFE treatment on human chondromalacic cartilage. Articular cartilage specimens were extracted (n = 50) from femoral condyle samples of patients undergoing total knee arthroplasty. Chondromalacia was graded with the Outerbridge classification system. Tissue thicknesses were measured using a needle punch test. Specimens underwent pretreatment load-relaxation testing using a spherical indenter. Bipolar RFE treatment was applied for 45 s and the indentation protocol was repeated. Structural properties were derived from the force-time data. Mechanical properties were derived using a fibril-reinforced biphasic cartilage model. Statistics were performed using repeated measures ANOVA. Cartilage thickness decreased after RFE treatment from a mean of 2.61 mm to 2.20 mm in Grade II, II-III, and III specimens (P < 0.001 each). Peak force increased after RFE treatment from a mean of 3.91 N to 4.91 N in Grade II and III specimens (P = 0.002 and P = 0.003, respectively). Equilibrium force increased after RFE treatment from a mean of 0.236 N to 0.457 N (P < 0.001 each grade). Time constant decreased after RFE treatment from a mean of 0.392 to 0.234 (P < 0.001 for each grade). Matrix modulus increased in all specimens following RFE treatment from a mean 259.12 kPa to 523.36 kPa (P < 0.001 each grade). Collagen fibril modulus decreased in Grade II and II-III specimens from 60.50 MPa to 42.04 MPa (P < 0.001 and P = 0.005, respectively). Tissue permeability decreased in Grade II and III specimens from 2.04 ∗10(-15) m(4)/Ns to 0.91 ∗10(-15) m(4)/Ns (P < 0.001 and P = 0.009, respectively). RFE treatment decreased thickness, time constant, fibril modulus, permeability, but increased peak force

  3. Decreased birefringence of the superficial zone collagen network in the canine knee (stifle) articular cartilage after long distance running training, detected by quantitative polarised light microscopy.

    PubMed Central

    Arokoski, J P; Hyttinen, M M; Lapveteläinen, T; Takács, P; Kosztáczky, B; Módis, L; Kovanen, V; Helminen, H

    1996-01-01

    OBJECTIVE: To investigate the effects of a one year programme of running training (up to 40 km/day for 15 weeks) on the spatial orientation pattern of collagen and glycosaminoglycans in articular cartilage in different parts of the knee (stifle) and shoulder joints of young beagle dogs. METHODS: Area specific measurements of the optical path difference (= retardation, gamma) and the cartilage zone thickness were performed using conventional procedures and a new computer based quantitative polarised light microscopy method. Transmission electron microscopy was used to determine the zonal volume density of collagen fibrils. The concentrations of collagen and hydroxypyridinium crosslinks were investigated biochemically. RESULTS: Running training decreased gamma by 24-34% (p < 0.05) in the superficial zone of the lateral femoral condyle articular cartilage and at the centre of the tibial condyles. Gamma of glycosaminoglycans decreased by 26% (p < 0.05) in the superficial zone of the lateral condyle of the femur, but at the same site the volume density of collagen fibrils was unchanged. Neither the collagen concentration nor the concentration of hydroxypyridinium crosslinks was altered as a result of running. In both control and runner dogs, the thickness and gamma values of the superficial zone were greater in the humerus and the femur than in the tibia. CONCLUSION: Endurance type running exercise in beagles caused a reduction in the superficial zone birefringence of the articular cartilage, which indicates either a disorganisation or a reorientation of the superficial zone collagen network. Articular cartilage showed marked variability of collagen network organisation over the different knee (stifle) joint articular surfaces. Images PMID:8733443

  4. Lectin affinity chromatography of articular cartilage fibromodulin: Some molecules have keratan sulphate chains exclusively capped by α(2-3)-linked sialic acid.

    PubMed

    Lauder, Robert M; Huckerby, Thomas N; Nieduszynski, Ian A

    2011-10-01

    Fibromodulin from bovine articular cartilage has been subjected to lectin affinity chromatography by Sambucus nigra lectin which binds α(2-6)- linked N-acetylneuraminic acid, and the structure of the keratan sulphate in the binding and non-binding fractions examined by keratanase II digestion and subsequent high pH anion exchange chromatography. It has been confirmed that the keratan sulphate chains attached to fibromodulin isolated from bovine articular cartilage may have the chain terminating N-acetylneuraminic acid residue α(2-3)- or α(2-6)-linked to the adjacent galactose residue. Although the abundance of α(2-6)-linked N-acetylneuraminic acid (ca. 22%) is such that this could cap one of the four chains in almost all fibromodulin molecules, it was found that ca. 34% of the fibromodulin proteoglycan molecules from bovine articular cartilage were capped exclusively with α(2-3)-linked N-acetylneuraminic acid. The remainder of the fibromodulin proteoglycans, which bound to the lectin had a mixture of α(2-3)- and α(2-6)-linked N-acetylneuraminic acid capping structures. The keratan sulphates attached to fibromodulin molecules capped exclusively with α(2-3)- linked N-acetylneuraminic acid were found to have a higher level of galactose sulphation than those from fibromodulin with both α(2-3)- and α(2-6)-linked N-acetylneuraminic acid caps, which bound to the Sambucus nigra lectin. In addition, both pools contained chains of similar length (ca. 8-9 disaccharides). Both also contained α(1-3)-linked fucose, showing that this feature does not co-distribute with α(2-6)-linked N-acetylneuraminic acid, although these two features are present only in mature articular cartilage. These data show that there are discrete populations of fibromodulin within articular cartilage, which may have differing impacts upon tissue processes.

  5. Usefulness of the photoacoustic measurement method for monitoring the regenerative process of full-thickness defects in articular cartilage using tissue-engineering technology

    NASA Astrophysics Data System (ADS)

    Ishihara, Miya; Sato, Masato; Sato, Shunichi; Kikuchi, Toshiyuki; Mitani, Genya; Kaneshiro, Nagatoshi; Ishihara, Masayuki; Mochida, Joji; Kikuchi, Makoto

    2005-04-01

    We demonstrated the capability of photoacoustic measurement for viscoelastic characterization. Since tissue viscoelasticity affects the propagation and attenuation of photoacoustic waves generated in the tissue, the relaxation times of the photoacoustic waves give the viscosity-elasticity ratio of the tissue. The relaxation times of photoacoustic waves of articular cartilage tissues engineered under various culture conditions were closely correlated with intrinsic viscosity-elasticity ratios measured by using a conventional viscoelastic analyzer (R > 0.98). In order to apply the photoacoustic measurement method to evaluation of the regeneration of articular cartilage as a method to validate the surgery, the method should enable not only evaluation of engineered tissue during cultivation in vitro but also evaluation after transplantation of engineered tissue in vivo. The aim of this study was to verify the usefulness of the photoacoustic method for repeated measurement of viscoelastic properties in order to evaluate the process of regeneration of a full-thickness defect in rabbit articular cartilage using allografted tissue-engineered cartilage. Photoacoustic waves were induced by 266- and 355-nm, 5-7 ns, light pulses delivered through an optical silica fiber from an Q-switched Nd:YAG laser and were detected by a piezoelectric transducer, which we had designed. About a 40% difference between the viscosity-elasticity ratio of allografted cartilage that of tissue surrounding the defect was shown just after surgery. The difference was significantly reduced at 4 and 12 postoperative weeks. Therefore, since the photoacoustic measurement method enables assessment of the progress of restoration of the viscoelasticity of articular cartilage, its main function, this method would be useful as an evaluation method in regenerative medicine.

  6. Age-related changes in the articular cartilage of the stifle joint in non-working and working German Shepherd dogs.

    PubMed

    Francuski, J V; Radovanović, A; Andrić, N; Krstić, V; Bogdanović, D; Hadzić, V; Todorović, V; Lazarević Macanović, M; Sourice Petit, S; Beck-Cormier, S; Guicheux, J; Gauthier, O; Kovacević Filipović, M

    2014-11-01

    The aims of this study were to define age-related histological changes in the articular cartilage of the stifle joint in non-chondrodystrophic dogs and to determine whether physical activity has a positive impact on preservation of cartilage structure during ageing. Twenty-eight German shepherd dogs were included in the study. These dogs had no evidence of joint inflammation as defined by clinical assessment, radiology and synovial fluid analysis (specifically absence of synovial fluid serum amyloid A). The dogs were grouped as young working (n ¼ 4), young non-working (n ¼ 5), aged working (n ¼ 13) and aged non-working (n ¼ 6) animals. Gross changes in the stifle joints were recorded and biopsy samples of femoral and tibial articular cartilage were evaluated for thickness; chondrocyte number, density, surface area and morphology; isogenous group morphology; tidemark integrity; subchondral bone structure; presence of proteoglycans/ glycosaminoglycans; and expression of type I, II and X collagens. The major age-related changes, not related to type of physical activity, included elevated chondrocyte density and thinning of tibial cartilage and increased chondrocyte surface area in the superficial and intermediate zone of the femoral cartilage. There was also expression of type X collagen in the femoral and tibial calcified and non-calcified cartilage; however, type X collagen was not detected in the superficial zone of old working dogs. Therefore, ageing, with or without physical activity, leads to slight cartilage degeneration, while physical activity modulates the synthesis of type X collagen in the superficial cartilage zone, partially preserving the structure of hyaline cartilage.

  7. Expression of α and β subunits of the integrin superfamily in articular cartilage from macroscopically normal and osteoarthritic human femoral heads

    PubMed Central

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

    1998-01-01

    OBJECTIVE—The objective of this study was to detail the topographical and zonal distribution of α and β subunits of the integrin superfamily in normal and osteoarthritic cartilage.
METHODS—Immunohistochemistry utilising antibodies towards α and β subunits was performed on cryostat sections of human articular cartilage from macroscopically normal (n = 6) and osteoarthritic (n = 6) femoral heads. Samples of articular cartilage were obtained from 12 topographically distinct sites from each femoral head. Each section was divided into zones (superficial, middle, deep) and staining scores were recorded.
RESULTS—Normal cartilage stained for integrin subunits α1, α5, αV, β1, β4, and β5, but not for α2, α3, α4, α6, β2, β3, and β6. Intact and non-intact residual cartilage from osteoarthritic femoral heads stained for α1, α2, α5, αV, β1, β4, and β5. Staining was occasionally seen for α4 and β2, but not for α3, α6, β3, and β6. There was no topographical variation in the staining for any of the subunits in either normal or osteoarthritic cartilage. The only subunit that displayed a zonal variation was αV; staining for this subunit was most pronounced in the superficial zone compared with the middle and deep zones.
CONCLUSION—Chondrocytes in normal and osteoarthritic cartilage express the integrin subunits α1, α5, αV, β1, β4, and β5. Chondrocytes in osteoarthritic cartilage, in addition, express the α2, α4, and β2 subunits. The αv subunit is expressed by more chondrocytes in the superficial zone in comparison with cells in the deeper zones. None of the subunits display topographical variation in expression.

 Keywords: cartilage; integrins; immunohistochemistry; osteoarthritis PMID:9741315

  8. Role of endochondral ossification of articular cartilage and functional adaptation of the subchondral plate in the development of fatigue microcracking of joints.

    PubMed

    Muir, P; McCarthy, J; Radtke, C L; Markel, M D; Santschi, E M; Scollay, M C; Kalscheur, V L

    2006-03-01

    The mechanisms that regulate functional adaptation of the articular ends of long bones are poorly understood. However, endochondral ossification of articular cartilage and modeling/remodeling of the subchondral plate and epiphyseal trabeculae are important components of the adaptive response. We performed a histologic study of the distal end of the third metacarpal/metatarsal bone of Thoroughbreds after bones were bulk-stained in basic fuchsin and calcified sections were prepared. The Thoroughbred racehorse is a model of an extreme athlete which experiences particularly high cyclic strains in distal limb bones. The following variables were quantified: microcrack boundary density in calcified cartilage (N.Cr/B.Bd); blood vessel boundary density in calcified cartilage (N.Ve/B.Bd); calcified cartilage width (Cl.Cg.Wi); duplication of the tidemark; and bone volume fraction of the subchondral plate (B.Ar/T.Ar). Measurements were made in five joint regions (lateral condyle and condylar groove; sagittal ridge; medial condylar and condylar groove). N.Cr/B.Bd was site-specific and was increased in the condylar groove region; this is the joint region from which parasagittal articular fatigue (condylar) fractures are typically propagated. Formation of resorption spaces in the subchondral plate was co-localized with microcracking. N.Ve/B.Bd was also site-specific. In the sagittal ridge region, N.Ve/B.Bd was increased, Cl.Cg.Wi was decreased, and B.Ar/T.Ar was decreased, when compared with the other joint regions. Multiple tidemarks were seen in all joint regions. Cumulative athletic activity was associated with a significant decrease in B.Ar/T.Ar in the condylar groove regions. N.Cr/B.Bd was positively correlated with B.Ar/T.Ar (P < 0.05, r(s) = 0.29) and N.Ve/B.Bd was negatively correlated with B.Ar/T.Ar (P < 0.005, r2 = 0.14) and Cl.Cg.Wi (P < 0.05, r2 = 0.07). We conclude that endochondral ossification of articular cartilage and modeling/remodeling of the subchondral plate

  9. Electric field stimulation can increase protein synthesis in articular cartilage explants.

    PubMed

    MacGinitie, L A; Gluzband, Y A; Grodzinsky, A J

    1994-03-01

    It has been hypothesized that the electric fields associated with the dynamic loading of cartilage may affect its growth, remodeling, and biosynthesis. While the application of exogenous fields has been shown to modulate cartilage biosynthesis, it is not known what range of field magnitudes and frequencies can alter biosynthesis and how they relate to the magnitudes and frequencies of endogenous fields. Such information is necessary to understand and identify mechanisms by which fields may act on cartilage metabolism. In this study, incorporation of 35S-methionine was used as a marker for electric field-induced changes in chondrocyte protein synthesis in disks of cartilage from the femoropatellar groove of 1 to 2-week-old calves. The cartilage was stimulated sinusoidally at 1, 10, 100, 10(3), and 10(4) Hz with current densities of 10-30 mA/cm2. Incorporation was assessed in control disks maintained in the absence of applied current at 37, 41, and 43 degrees C. The possibility that applied currents would induce synthesis of the same stress proteins that are caused by heating or other mechanisms was assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and examination of gel fluorographs. Total radiolabel incorporation in cartilage that had been stimulated relative to incorporation in the controls increased with current density magnitudes greater than 10 mA/cm2. The increase was greatest at 100 Hz and 1 kHz, and it depended on the position on the joint surface from which the cartilage samples were taken. Together, these results suggest that endogenous electric fields could affect cartilage biosynthesis. Stress proteins were not induced at any current density when the electrodes were electrically connected but chemically isolated from the media by agarose bridges. Stress proteins were observed for disks incubated at temperatures greater than 39 degrees C (no field) and when the stimulating platinum electrodes were in direct contact with the media

  10. Articular cartilage wear characterization with a particle sizing and counting analyzer.

    PubMed

    Oungoulian, Sevan R; Chang, Stephany; Bortz, Orian; Hehir, Kristin E; Zhu, Kaicen; Willis, Callen E; Hung, Clark T; Ateshian, Gerard A

    2013-02-01

    Quantitative measurements of cartilage wear have been challenging, with no method having yet emerged as a standard. This study tested the hypothesis that latest-generation particle analyzers are capable of detecting cartilage wear debris generated during in vitro loading experiments that last 24 h or less, by producing measurable content significantly above background noise levels otherwise undetectable through standard biochemical assays. Immature bovine cartilage disks (4 mm diameter, 1.3 mm thick) were tested against glass using reciprocal sliding under unconfined compression creep for 24 h. Control groups were used to assess various sources of contamination. Results demonstrated that cartilage samples subjected to frictional loading produced particulate volume significantly higher than background noise and contamination levels at all tested time points (1, 2, 6, and 24 h, p < 0.042). The particle counter was able to detect very small levels of wear (less than 0.02% of the tissue sample by volume), whereas no significant differences were observed in biochemical assays for collagen or glycosaminoglycans among any of the groups or time points. These findings confirm that latest-generation particle analyzers are capable of detecting very low wear levels in cartilage experiments conducted over a period no greater than 24 h.

  11. Nanomechanics of Murine Articular Cartilage Reveals the Effects of Chondroadherin Knockouts

    NASA Astrophysics Data System (ADS)

    Batista, Michael; Grodzinsky, Alan; Ortiz, Christine; Heinegård, Dick; Han, Lin

    2012-02-01

    With high resolution nanotechnology tools, quantification of cartilage biomechanical properties provides important insights into the role of low abundance matrix molecules on cartilage function and pathology. In this study, the role of chondroadherin (CHAD) on cartilage mechanical properties was assessed via atomic force microscopy-based nanoindentation (0.1-10 μm/s z-piezo displacement rates) of murine knee cartilage from wild type (WT) and CHAD knockout (KO) animals ages 1 year, 4 month, and 11 weeks (n>=4 joints/age-group). A significant increase in indentation modulus, E, with indentation rate in all specimens (p<0.05, Friedman) suggested poro-viscoelastic behavior. For all age groups, CHAD KO significantly reduced E at all indentation rates (p<0.05, 2-way ANOVA); e.g., at 1-year, E was 0.77+/-0.1 MPa for WT (mean+/-SEM 1μm/s rate) and 0.25+/-0.07 MPa for CHAD KO cartilage. Lack of CHAD appears to delay development of load bearing extracellular matrix. This could affect the effective cross-link density of the tissue network and, hence, decrease local osmotic swelling while increasing the hydraulic permeability of the aggrecan-filled network. Ongoing studies are investigating the biochemical properties and nanostructure of CHAD KO joints.

  12. Automating measurement of subtle changes in articular cartilage from MRI of the knee by combining 3D image registration and segmentation

    NASA Astrophysics Data System (ADS)

    Lynch, John A.; Zaim, Souhil; Zhao, Jenny; Peterfy, Charles G.; Genant, Harry K.

    2001-07-01

    In osteoarthritis, articular cartilage loses integrity and becomes thinned. This usually occurs at sites which bear weight during normal use. Measurement of such loss from MRI scans, requires precise and reproducible techniques, which can overcome the difficulties of patient repositioning within the scanner. In this study, we combine a previously described technique for segmentation of cartilage from MRI of the knee, with a technique for 3D image registration that matches localized regions of interest at followup and baseline. Two patients, who had recently undergone meniscal surgery, and developed lesions during the 12 month followup period were examined. Image registration matched regions of interest (ROI) between baseline and followup, and changes within the cartilage lesions were estimate to be about a 16% reduction in cartilage volume within each ROI. This was more than 5 times the reproducibility of the measurement, but only represented a change of between 1 and 2% in total femoral cartilage volume. Changes in total cartilage volume may be insensitive for quantifying changes in cartilage morphology. A combined used of automated image segmentation, with 3D image registration could be a useful tool for the precise and sensitive measurement of localized changes in cartilage from MRI of the knee.

  13. Characterization of Selective Exosite-Binding Inhibitors of Matrix Metalloproteinase 13 That Prevent Articular Cartilage Degradation in Vitro

    PubMed Central

    2015-01-01

    Matrix metalloproteinase 13 (MMP-13) has been shown to be the main collagenase responsible for degradation of articular cartilage during osteoarthritis and therefore represents a target for drug development. As a result of high-throughput screening and structure–activity relationship studies, we identified a novel, highly selective class of MMP-13 inhibitors (compounds 1 (Q), 2 (Q1), and 3 (Q2)). Mechanistic characterization revealed a noncompetitive nature of these inhibitors with binding constants in the low micromolar range. Crystallographic analyses revealed two binding modes for compound 2 in the MMP-13 S1′ subsite and in an S1/S2* subsite. Type II collagen- and cartilage-protective effects exhibited by compounds 1, 2, and 3 suggested that these compounds might be efficacious in future in vivo studies. Finally, these compounds were also highly selective when tested against a panel of 30 proteases, which, in combination with a good CYP inhibition profile, suggested low off-target toxicity and drug–drug interactions in humans. PMID:25330343

  14. Chemical imaging of articular cartilage sections with Raman mapping, employing uni- and multi-variate methods for data analysis.

    PubMed

    Bonifacio, Alois; Beleites, Claudia; Vittur, Franco; Marsich, Eleonora; Semeraro, Sabrina; Paoletti, Sergio; Sergo, Valter

    2010-12-01

    Raman mapping in combination with uni- and multi-variate methods of data analysis is applied to articular cartilage samples. Main differences in biochemical composition and collagen fibers orientation between superficial, middle and deep zone of the tissue are readily observed in the samples. Collagen, non-collagenous proteins, proteoglycans and nucleic acids can be distinguished on the basis of their different spectral characteristics, and their relative abundance can be mapped in the label-free tissue samples, at so high a resolution as to permit the analysis at the level of single cells. Differences between territorial and inter-territorial matrix, as well as inhomogeneities in the inter-territorial matrix, are properly identified. Multivariate methods of data analysis prove to be complementary to the univariate approach. In particular, our partial least squares regression model gives a semiquantitative mapping of the biochemical constituents in agreement with average composition found in the literature. The combination of hierarchical and fuzzy cluster analysis succeeds in detecting variations between different regions of the extra-cellular matrix. Because of its characteristics as an imaging technique, Raman mapping could be a promising tool for studying biochemical changes in cartilage occurring during aging or osteoarthritis.

  15. Changes in chondrocyte gene expression following in vitro impaction of porcine articular cartilage in an impact injury model.

    PubMed

    Ashwell, Melissa S; Gonda, Michael G; Gray, Kent; Maltecca, Christian; O'Nan, Audrey T; Cassady, Joseph P; Mente, Peter L

    2013-03-01

    Our objective was to monitor chondrocyte gene expression at 0, 3, 7, and 14 days following in vitro impaction to the articular surface of porcine patellae. Patellar facets were either axially impacted with a cylindrical impactor (25 mm/s loading rate) to a load level of 2,000 N or not impacted to serve as controls. After being placed in organ culture for 0, 3, 7, or 14 days, total RNA was isolated from full thickness cartilage slices and gene expression measured for 17 genes by quantitative real-time RT-PCR. Targeted genes included those encoding proteins involved with biological stress, inflammation, or anabolism and catabolism of cartilage extracellular matrix. Some gene expression changes were detected on the day of impaction, but most significant changes occurred at 14 days in culture. At 14 days in culture, 10 of the 17 genes were differentially expressed with col1a1 most significantly up-regulated in the impacted samples, suggesting impacted chondrocytes may have reverted to a fibroblast-like phenotype.

  16. Characterization of selective exosite-binding inhibitors of matrix metalloproteinase 13 that prevent articular cartilage degradation in vitro.

    PubMed

    Spicer, Timothy P; Jiang, Jianwen; Taylor, Alexander B; Choi, Jun Yong; Hart, P John; Roush, William R; Fields, Gregg B; Hodder, Peter S; Minond, Dmitriy

    2014-11-26

    Matrix metalloproteinase 13 (MMP-13) has been shown to be the main collagenase responsible for degradation of articular cartilage during osteoarthritis and therefore represents a target for drug development. As a result of high-throughput screening and structure-activity relationship studies, we identified a novel, highly selective class of MMP-13 inhibitors (compounds 1 (Q), 2 (Q1), and 3 (Q2)). Mechanistic characterization revealed a noncompetitive nature of these inhibitors with binding constants in the low micromolar range. Crystallographic analyses revealed two binding modes for compound 2 in the MMP-13 S1' subsite and in an S1/S2* subsite. Type II collagen- and cartilage-protective effects exhibited by compounds 1, 2, and 3 suggested that these compounds might be efficacious in future in vivo studies. Finally, these compounds were also highly selective when tested against a panel of 30 proteases, which, in combination with a good CYP inhibition profile, suggested low off-target toxicity and drug-drug interactions in humans.

  17. Automatic Segmentation and Quantitative Analysis of the Articular Cartilages From Magnetic Resonance Images of the Knee

    PubMed Central

    Fripp, Jurgen; Crozier, Stuart; Warfield, Simon K.; Ourselin, Sébastien

    2010-01-01

    In this paper, we present a segmentation scheme that automatically and accurately segments all the cartilages from magnetic resonance (MR) images of nonpathological knees. Our scheme involves the automatic segmentation of the bones using a three-dimensional active shape model, the extraction of the expected bone-cartilage interface (BCI), and cartilage segmentation from the BCI using a deformable model that utilizes localization, patient specific tissue estimation and a model of the thickness variation. The accuracy of this scheme was experimentally validated using leave one out experiments on a database of fat suppressed spoiled gradient recall MR images. The scheme was compared to three state of the art approaches, tissue classification, a modified semi-automatic watershed algorithm and nonrigid registration (B-spline based free form deformation). Our scheme obtained an average Dice similarity coefficient (DSC) of (0.83, 0.83, 0.85) for the (patellar, tibial, femoral) cartilages, while (0.82, 0.81, 0.86) was obtained with a tissue classifier and (0.73, 0.79, 0.76) was obtained with nonrigid registration. The average DSC obtained for all the cartilages using a semi-automatic watershed algorithm (0.90) was slightly higher than our approach (0.89), however unlike this approach we segment each cartilage as a separate object. The effectiveness of our approach for quantitative analysis was evaluated using volume and thickness measures with a median volume difference error of (5.92, 4.65, 5.69) and absolute Laplacian thickness difference of (0.13, 0.24, 0.12) mm. PMID:19520633

  18. Articular cartilage repair with recombinant human type II collagen/polylactide scaffold in a preliminary porcine study.

    PubMed

    Muhonen, Virpi; Salonius, Eve; Haaparanta, Anne-Marie; Järvinen, Elina; Paatela, Teemu; Meller, Anna; Hannula, Markus; Björkman, Mimmi; Pyhältö, Tuomo; Ellä, Ville; Vasara, Anna; Töyräs, Juha; Kellomäki, Minna; Kiviranta, Ilkka

    2016-05-01

    The purpose of this study was to investigate the potential of a novel recombinant human type II collagen/polylactide scaffold (rhCo-PLA) in the repair of full-thickness cartilage lesions with autologous chondrocyte implantation technique (ACI). The forming repair tissue was compared to spontaneous healing (spontaneous) and repair with a commercial porcine type I/III collagen membrane (pCo). Domestic pigs (4-month-old, n = 20) were randomized into three study groups and a circular full-thickness chondral lesion with a diameter of 8 mm was created in the right medial femoral condyle. After 3 weeks, the chondral lesions were repaired with either rhCo-PLA or pCo together with autologous chondrocytes, or the lesion was only debrided and left untreated for spontaneous repair. The repair tissue was evaluated 4 months after the second operation. Hyaline cartilage formed most frequently in the rhCo-PLA treatment group. Biomechanically, there was a trend that both treatment groups resulted in better repair tissue than spontaneous healing. Adverse subchondral bone reactions developed less frequently in the spontaneous group (40%) and the rhCo-PLA treated group (50%) than in the pCo control group (100%). However, no statistically significant differences were found between the groups. The novel rhCo-PLA biomaterial showed promising results in this proof-of-concept study, but further studies will be needed in order to determine its effectiveness in articular cartilage repair. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:745-753, 2016.

  19. Attenuation of the progression of articular cartilage degeneration by inhibition of TGF-β1 signaling in a mouse model of osteoarthritis.

    PubMed

    Chen, Rebecca; Mian, Michelle; Fu, Martin; Zhao, Jing Ying; Yang, Liang; Li, Yefu; Xu, Lin

    2015-11-01

    Transforming growth factor beta 1 (TGF-β1) is implicated in osteoarthritis. We therefore studied the role of TGF-β1 signaling in the development of osteoarthritis in a developmental stage-dependent manner. Three different mouse models were investigated. First, the Tgf-β receptor II (Tgfbr2) was specifically removed from the mature cartilage of joints. Tgfbr2-deficient mice were grown to 12 months of age and were then euthanized for collection of knee and temporomandibular joints. Second, Tgfbr2-deficient mice were subjected to destabilization of the medial meniscus (DMM) surgery. Knee joints were then collected from the mice at 8 and 16 weeks after the surgery. Third, wild-type mice were subjected to DMM at the age of 8 weeks. Immediately after the surgery, these mice were treated with the Tgfbr2 inhibitor losartan for 8 weeks and then euthanized for collection of knee joints. All joints were characterized for evidences of articular cartilage degeneration. Initiation or acceleration of articular cartilage degeneration was not observed by the genetic inactivation of Tgfbr2 in the joints at the age of 12 months. In fact, the removal of Tgfbr2 and treatment with losartan both delayed the progression of articular cartilage degeneration induced by DMM compared with control littermates. Therefore, we conclude that inhibition of Tgf-β1 signaling protects adult knee joints in mice against the development of osteoarthritis.

  20. Feasibility of high-resolution one-dimensional relaxation imaging at low magnetic field using a single-sided NMR scanner applied to articular cartilage

    NASA Astrophysics Data System (ADS)

    Rössler, Erik; Mattea, Carlos; Stapf, Siegfried

    2015-02-01

    Low field Nuclear Magnetic Resonance increases the contrast of the longitudinal relaxation rate in many biological tissues; one prominent example is hyaline articular cartilage. In order to take advantage of this increased contrast and to profile the depth-dependent variations, high resolution parameter measurements are carried out which can be of critical importance in an early diagnosis of cartilage diseases such as osteoarthritis. However, the maximum achievable spatial resolution of parameter profiles is limited by factors such as sensor geometry, sample curvature, and diffusion limitation. In this work, we report on high-resolution single-sided NMR scanner measurements with a commercial device, and quantify these limitations. The highest achievable spatial resolution on the used profiler, and the lateral dimension of the sensitive volume were determined. Since articular cartilage samples are usually bent, we also focus on averaging effects inside the horizontally aligned sensitive volume and their impact on the relaxation profiles. Taking these critical parameters into consideration, depth-dependent relaxation time profiles with the maximum achievable vertical resolution of 20 μm are discussed, and are correlated with diffusion coefficient profiles in hyaline articular cartilage in order to reconstruct T2 maps from the diffusion-weighted CPMG decays of apparent relaxation rates.

  1. The repair of full-thickness articular cartilage defects. Immune responses to reparative tissue formed by allogeneic growth plate chondrocyte implants

    SciTech Connect

    Kawabe, N.; Yoshinao, M. )

    1991-07-01

    Growth plate cartilage cultivated in vitro was attached with a fibrin clot to a full-thickness articular cartilage defect on knee joints in allogeneic New Zealand rabbits. The healing of the defects was assessed by gross examination, light microscopy, and immunologic analysis for 24 weeks. Immunologic assessment of cell-mediated immunity, cytotoxicity of a humoral antibody by a 51 chromium release assay, and immunofluorescence studies were carried out. During the first two weeks following grafting, healing was excellent in 11 of the 17 defects. From three to 24 weeks, 11 of 42 defects examined had good results. Host lymphocytes had accumulated around the allograft at two to 12 weeks. Most of the implanted cartilage grown in vitro died and was replaced by fibrous tissue. The immunologic studies suggested that the implanted cartilage began to degenerate two to three weeks after implantation partially because of a humoral immune response but more importantly because of cell-mediated cytotoxicity.

  2. Effect of Human Adipose Tissue Mesenchymal Stem Cells on the Regeneration of Ovine Articular Cartilage

    PubMed Central

    Zorzi, Alessandro R.; Amstalden, Eliane M. I.; Plepis, Ana Maria G.; Martins, Virginia C. A.; Ferretti, Mario; Antonioli, Eliane; Duarte, Adriana S. S.; Luzo, Angela C. M.; Miranda, João B.

    2015-01-01

    Cell therapy is a promising approach to improve cartilage healing. Adipose tissue is an abundant and readily accessible cell source. Previous studies have demonstrated good cartilage repair results with adipose tissue mesenchymal stem cells in small animal experiments. This study aimed to examine these cells in a large animal model. Thirty knees of adult sheep were randomly allocated to three treatment groups: CELLS (scaffold seeded with human adipose tissue mesenchymal stem cells), SCAFFOLD (scaffold without cells), or EMPTY (untreated lesions). A partial thickness defect was created in the medial femoral condyle. After six months, the knees were examined according to an adaptation of the International Cartilage Repair Society (ICRS 1) score, in addition to a new Partial Thickness Model scale and the ICRS macroscopic score. All of the animals completed the follow-up period. The CELLS group presented with the highest ICRS 1 score (8.3 ± 3.1), followed by the SCAFFOLD group (5.6 ± 2.2) and the EMPTY group (5.2 ± 2.4) (p = 0.033). Other scores were not significantly different. These results suggest that human adipose tissue mesenchymal stem cells promoted satisfactory cartilage repair in the ovine model. PMID:26569221

  3. Ensemble multivariate analysis to improve identification of articular cartilage disease in noisy Raman spectra.

    PubMed

    Richardson, Wade; Wilkinson, Dan; Wu, Ling; Petrigliano, Frank; Dunn, Bruce; Evseenko, Denis

    2015-07-01

    The development of new methods for the early diagnosis of cartilage disease could offer significant improvement in patient care. Raman spectroscopy is an emerging biomedical technology with unique potential to recognize disease tissues, though difficulty in obtaining the samples needed to train a diagnostic and excessive signal noise could slow its development into a clinical tool. In the current report we detail the use of principal component analysis--linear discriminant analysis (PCA-LDA) on spectra from pairs of materials modeling cartilage disease to create multiple spectral scoring metrics, which could limit the reliance on primary training data for identifying disease in low signal-to-noise-ratio (SNR) Raman spectra. Our proof-of-concept experiments show that combinations of these model-metrics has the potential to improve the classification of low-SNR Raman spectra from human normal and osteoarthritic (OA) cartilage over a single metric trained with spectra from the same healthy and OA tissues. Scatter plot showing the PCA-LDA derived human-disease-metric scores versus rat-model-metric scores for 7656 low signal-to-noise spectra from healthy (blue) and osteoarthritic (red) cartilage. Light vertical and horizontal lines represent the optimized single metric classification boundary. Dark diagonal line represents the classification of boundary resulting from the optimized combination of the two metrics.

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

    PubMed

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

    2016-11-01

    We previously showed that repetitive cyclic loading of the mouse knee joint causes changes that recapitulate the features of osteoarthritis (OA) in humans. By applying a single loading session, we characterized the temporal progression of the structural and compositional changes in subchondral bone and articular cartilage. We applied loading during a single 5-minute session to the left tibia of adult (26-week-old) C57Bl/6 male mice at a peak load of 9.0N for 1,200 cycles. Knee joints were collected at times 0, 1, and 2 weeks after loading. The changes in articular cartilage and subchondral bone were analyzed by histology, immunohistochemistry (caspase-3 and cathepsin K), and microcomputed tomography. At time 0, no change was evident in chondrocyte viability or cartilage or subchondral bone integrity. However, cartilage pathology demonstrated by localized thinning and proteoglycan loss occurred at 1 and 2 weeks after the single session of loading. Transient cancellous bone loss was evident at 1 week, associated with increased osteoclast number. Bone loss was reversed to control levels at 2 weeks. We observed formation of fibrous and cartilaginous tissues at the joint margins at 1 and 2 weeks. Our findings demonstrate that a single session of noninvasive loading leads to the development of OA-like morphological and cellular alterations in articular cartilage and subchondral bone. The loss in subchondral trabecular bone mass and thickness returns to control levels at 2 weeks, whereas the cartilage thinning and proteoglycan loss persist. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1941-1949, 2016.

  5. Repair of porcine articular cartilage defect with a biphasic osteochondral composite.

    PubMed

    Jiang, Ching-Chuan; Chiang, Hongsen; Liao, Chun-Jen; Lin, Yu-Ju; Kuo, Tzong-Fu; Shieh, Chang-Shun; Huang, Yi-You; Tuan, Rocky S

    2007-10-01

    Autologous chondrocyte implantation (ACI) has been recently used to treat cartilage defects. Partly because of the success of mosaicplasty, a procedure that involves the implantation of native osteochondral plugs, it is of potential significance to consider the application of ACI in the form of biphasic osteochondral composites. To test the clinical applicability of such composite construct, we repaired osteochondral defect with ACI at low cell-seeding density on a biphasic scaffold, and combined graft harvest and implantation in a single surgery. We fabricated a biphasic cylindrical porous plug of DL-poly-lactide-co-glycolide, with its lower body impregnated with beta-tricalcium phosphate as the osseous phase. Osteochondral defects were surgically created at the weight-bearing surface of femoral condyles of Lee-Sung mini-pigs. Autologous chondrocytes isolated from the cartilage were seeded into the upper, chondral phase of the plug, which was inserted by press-fitting to fill the defect. Defects treated with cell-free plugs served as control. Outcome of repair was examined 6 months after surgery. In the osseous phase, the biomaterial retained in the center and cancellous bone formed in the periphery, integrating well with native subchondral bone with extensive remodeling, as depicted on X-ray roentgenography by higher radiolucency. In the chondral phase, collagen type II immunohistochemistry and Safranin O histological staining showed hyaline cartilage regeneration in the experimental group, whereas only fibrous tissue formed in the control group. On the International Cartilage Repair Society Scale, the experimental group had higher mean scores in surface, matrix, cell distribution, and cell viability than control, but was comparable with the control group in subchondral bone and mineralization. Tensile stress-relaxation behavior determined by uni-axial indentation test revealed similar creep property between the surface of the experimental specimen and native

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

    PubMed

    Haider, Mansoor A; Guilak, Farshid

    2007-06-15

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

  7. Multiscale Strain as a Predictor of Impact-Induced Fissuring in Articular Cartilage.

    PubMed

    Henak, Corinne R; Bartell, Lena R; Cohen, Itai; Bonassar, Lawrence J

    2017-03-01

    Mechanical damage is central to both initiation and progression of osteoarthritis (OA). However, specific causal links between mechanics and cartilage damage are incompletely understood, which results in an inability to predict failure. The lack of understanding is primarily due to the difficulty in simultaneously resolving the high rates and small length scales relevant to the problem and in correlating such measurements to the resulting fissures. This study leveraged microscopy and high-speed imaging to resolve mechanics on the previously unexamined time and length scales of interest in cartilage damage, and used those mechanics to develop predictive models. The specific objectives of this study were to: first, quantify bulk and local mechanics during impact-induced fissuring; second, develop predictive models of fissuring based on bulk mechanics and local strain; and third, evaluate the accuracy of these models in predicting fissures. To achieve these three objectives, bovine tibial cartilage was impacted using a custom spring-loaded device mounted on an inverted microscope. The occurrence of fissures was modulated by varying impact energy. For the first objective, during impact, deformation was captured at 10,000 frames per second and bulk and local mechanics were analyzed. For the second objective, data from samples impacted with a 1.2 mm diameter rod were fit to logistic regression functions, creating models of fissure probability based on bulk and local mechanics. Finally, for the third objective, data from samples impacted with a 0.8 mm diameter rod were used to test the accuracy of model predictions. This study provides a direct comparison between bulk and local mechanical thresholds for the prediction of fissures in cartilage samples, and demonstrates that local mechanics provide more accurate predictions of local failure than bulk mechanics provide. Bulk mechanics were accurate predictors of fissure for the entire sample cohort, but poor predictors

  8. Allogeneic Bone Marrow Transplant from MRL/MpJ Super-Healer Mice Does Not Improve Articular Cartilage Repair in the C57Bl/6 Strain

    PubMed Central

    Leonard, Catherine A.; Lee, Woo-Yong; Tailor, Pankaj; Salo, Paul T.; Kubes, Paul; Krawetz, Roman J.

    2015-01-01

    Background Articular cartilage has been the focus of multiple strategies to improve its regenerative/ repair capacity. The Murphy Roths Large (MRL/MpJ) “super-healer” mouse demonstrates an unusual enhanced regenerative capacity in many tissues and provides an opportunity to further study endogenous cartilage repair. The objective of this study was to test whether the super-healer phenotype could be transferred from MRL/MpJ to non-healer C57Bl/6 mice by allogeneic bone marrow transplant. Methodology The healing of 2mm ear punches and full thickness cartilage defects was measured 4 and 8 weeks after injury in control C57Bl/6 and MRL/MpJ “super-healer” mice, and in radiation chimeras reconstituted with bone marrow from the other mouse strain. Healing was assessed using ear hole diameter measurement, a 14 point histological scoring scale for the cartilage defect and an adapted version of the Osteoarthritis Research Society International scale for assessment of osteoarthritis in mouse knee joints. Principal Findings Normal and chimeric MRL mice showed significantly better healing of articular cartilage and ear wounds along with less severe signs of osteoarthritis after cartilage injury than the control strain. Contrary to our hypothesis, however, bone marrow transplant from MRL mice did not confer improved healing on the C57Bl/6 chimeras, either in regards to ear wound healing or cartilage repair. Conclusion and Significance The elusive cellular basis for the MRL regenerative phenotype still requires additional study and may possibly be dependent on additional cell types external to the bone marrow. PMID:26120841

  9. Measuring microscale strain fields in articular cartilage during rapid impact reveals thresholds for chondrocyte death and a protective role for the superficial layer

    PubMed Central

    Bartell, Lena R.; Fortier, Lisa A.; Bonassar, Lawrence J.; Cohen, Itai

    2015-01-01

    Articular cartilage is a heterogeneous soft tissue that dissipates and distributes loads in mammalian joints. Though robust, cartilage is susceptible to damage from loading at high rates or magnitudes. Such injurious loads have been implicated in degenerative changes, including chronic osteoarthritis (OA), which remains a leading cause of disability in developed nations. Despite decades of research, mechanisms of OA initiation after trauma remain poorly understood. Indeed, although bulk cartilage mechanics are measurable during impact, current techniques cannot access microscale mechanics at those rapid time scales. We aimed to address this knowledge gap by imaging the microscale mechanics and corresponding acute biological changes of cartilage in response to rapid loading. In this study, we utilized fast-camera and confocal microscopy to achieve roughly 85 μm spatial resolution of the cartilage deformation during a rapid (~3 ms), localized impact and the chondrocyte death following impact. Our results showed that, at these high rates, strain and chondrocyte death were highly correlated (p<0.001) with a threshold of 8% microscale strain norm before any cell death occurred. Additionally, chondrocyte death had developed by two hours after impact, suggesting a time frame for clinical therapeutics. Moreover, when the superficial layer was removed, strain – and subsequently chondrocyte death – penetrated deeper into the samples (p<0.001), suggesting a protective role for the superficial layer of articular cartilage. Combined, these results provide insight regarding the detailed biomechanics that drive early chondrocyte damage after trauma and emphasize the importance of understanding cartilage and its mechanics on the microscale. PMID:26150096

  10. Characterization of Tissue Response to Impact Loads Delivered Using a Hand-Held Instrument for Studying Articular Cartilage Injury

    PubMed Central

    Bonnevie, Edward D.; Delco, Michelle L.; Fortier, Lisa A.; Alexander, Peter G.; Tuan, Rocky S.

    2015-01-01

    Objective: The objective of this study was to fully characterize the mechanics of an in vivo impactor and correlate the mechanics with superficial cracking of articular surfaces. Design: A spring-loaded impactor was used to apply energy-controlled impacts to the articular surfaces of neonatal bovine cartilage. The simultaneous use of a load cell and displacement sensor provided measurements of stress, stress rate, strain, strain rate, and strain energy density. Application of India ink after impact was used to correlate the mechanical inputs during impact with the resulting severity of tissue damage. Additionally, a signal processing method to deconvolve inertial stresses from impact stresses was developed and validated. Results: Impact models fit the data well (root mean square error average ~0.09) and provided a fully characterized impact. Correlation analysis between mechanical inputs and degree of superficial cracking made visible through India ink application provided significant positive correlations for stress and stress rate with degree of surface cracking (R2 = 0.7398 and R2 = 0.5262, respectively). Ranges of impact parameters were 7 to 21 MPa, 6 to 40 GPa/s, 0.16 to 0.38, 87 to 236 s−1, and 0.3 to 1.1 MJ/m3 for stress, stress rate, strain, strain rate, and strain energy density, respectively. Thresholds for damage for all inputs were determined at 13 MPa, 15 GPa/s, 0.23, 160 s−1, and 0.59 MJ/m3 for this system. Conclusions: This study provided the mechanical basis for use of a portable, sterilizable, and maneuverable impacting device. Use of this device enables controlled impact loads in vitro or in vivo to connect mechanistic studies with long-term monitoring of disease progression. PMID:26425260

  11. Differential Gene Expression of the Intermediate and Outer Interzone Layers of Developing Articular Cartilage in Murine Embryos

    PubMed Central

    IJpma, Arne; Cleary, Mairead; Heijsman, Daphne; Narcisi, Roberto; van der Spek, Peter J.; Kremer, Andreas; van Weeren, René; Brama, Pieter; van Osch, Gerjo J.V.M.

    2014-01-01

    Nascent embryonic joints, interzones, contain a distinct cohort of progenitor cells responsible for the formation of the majority of articular tissues. However, to date the interzone has largely been studied using in situ analysis for candidate genes in the context of the embryo rather than using an unbiased genome-wide expression analysis on isolated interzone cells, leaving significant controversy regarding the exact role of the intermediate and outer interzone layers in joint formation. Therefore, in this study, using laser capture microdissection (three biological replicates), we selectively harvested the intermediate and outer interzones of mouse embryos at gestational age 15.5 days, just prior to cavitation, when the differences between the layers should be most profound. Microarray analysis (Agilent Whole Mouse Genome Oligo Microarrays) was performed and the differential gene expression between the intermediate interzone cells and outer interzone cells was examined by performing a two-sided paired Student's t-test and pathway analysis. One hundred ninety-seven genes were differentially expressed (≥2-fold) between the intermediate interzone and the outer interzone with a P-value≤0.01. Of these, 91 genes showed higher expression levels in the intermediate interzone and 106 were expressed higher in the outer interzone. Pathway analysis of differentially expressed genes suggests an important role for inflammatory processes in the interzone layers, especially in the intermediate interzone, and hence in joint and articular cartilage development. The high representation of genes relevant to chondrocyte hypertrophy and endochondral ossification in the outer interzone suggests that it undergoes endochondral ossification. PMID:24738827

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

    NASA Technical Reports Server (NTRS)

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

    2005-01-01

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

  13. Effects of Equine Joint Injury on Boundary Lubrication of Articular Cartilage by Synovial Fluid: Role of Hyaluronan

    PubMed Central

    Antonacci, Jennifer M.; Schmidt, Tannin A.; Serventi, Lisa A.; Cai, Matthew Z.; Shu, YuYu L.; Schumacher, Barbara L.; McIlwraith, C. Wayne; Sah, Robert L.

    2012-01-01

    Objective To compare equine synovial fluid (eSF) from post-injury and control joints for (1) cartilage boundary lubrication function, (2) putative boundary lubricant molecules hyaluronan (HA), proteoglycan-4 (PRG4), and surface-active phospholipids (SAPL), (3) relationships between lubrication function and composition, and (4) lubrication restoration by addition of HA. Methods eSF from normal (NL), acute injury (AI), and chronic injury (CI) joints were analyzed for boundary lubrication of normal articular cartilage as kinetic friction coefficient (μkinetic). eSF were also analyzed for HA, PRG4, and SAPL concentrations and HA molecular weight (MW) distribution. The effect of addition of HA, of different concentrations and MW, to AI- and NL-eSF samples on μkinetic was determined. Results The μkinetic of AI-eSF (0.036) was higher (+39%) than that of NL-eSF (0.026). Compared to NL-eSF, AI-eSF had a lower HA concentration (−30%) of lower MW forms, higher PRG4 concentration (+83%), and higher SAPL concentration (+144%). CI-eSF had μkinetic, HA, PRG4, and SAPL characteristics intermediate to that of AI-eSF and NL-eSF. Regression analysis revealed that μkinetic decreased with increasing HA concentration in eSF. The friction-reducing properties of HA alone improved with increasing concentration and MW. Addition of high-MW HA (4,000kDa) to AI-eSF reduced μkinetic to a value near that of NL-eSF. Conclusion In the acute post-injury stage, eSF exhibits poor boundary lubrication properties as indicated by a high μkinetic. HA of diminished concentration and MW may be the basis for this, and adding HA to deficient eSF restored lubrication function. PMID:22605527

  14. A concurrent computer aided detection (CAD) tool for articular cartilage disease of the knee on MR imaging using active shape models

    NASA Astrophysics Data System (ADS)

    Ramakrishna, Bharath; Saiprasad, Ganesh; Safdar, Nabile; Siddiqui, Khan; Chang, Chein-I.; Siegel, Eliot

    2008-03-01

    Osteoarthritis (OA) is the most common form of arthritis and a major cause of morbidity affecting millions of adults in the US and world wide. In the knee, OA begins with the degeneration of joint articular cartilage, eventually resulting in the femur and tibia coming in contact, and leading to severe pain and stiffness. There has been extensive research examining 3D MR imaging sequences and automatic/semi-automatic techniques for 2D/3D articular cartilage extraction. However, in routine clinical practice the most popular technique still remain radiographic examination and qualitative assessment of the joint space. This may be in large part because of a lack of tools that can provide clinically relevant diagnosis in adjunct (in near real time fashion) with the radiologist and which can serve the needs of the radiologists and reduce inter-observer variation. Our work aims to fill this void by developing a CAD application that can generate clinically relevant diagnosis of the articular cartilage damage in near real time fashion. The algorithm features a 2D Active Shape Model (ASM) for modeling the bone-cartilage interface on all the slices of a Double Echo Steady State (DESS) MR sequence, followed by measurement of the cartilage thickness from the surface of the bone, and finally by the identification of regions of abnormal thinness and focal/degenerative lesions. A preliminary evaluation of CAD tool was carried out on 10 cases taken from the Osteoarthritis Initiative (OAI) database. When compared with 2 board-certified musculoskeletal radiologists, the automatic CAD application was able to get segmentation/thickness maps in little over 60 seconds for all of the cases. This observation poses interesting possibilities for increasing radiologist productivity and confidence, improving patient outcomes, and applying more sophisticated CAD algorithms to routine orthopedic imaging tasks.

  15. Functional tissue engineering in articular cartilage repair: is there a role for electromagnetic biophysical stimulation?

    PubMed

    Fini, Milena; Pagani, Stefania; Giavaresi, Gianluca; De Mattei, Monica; Ongaro, Alessia; Varani, Katia; Vincenzi, Fabrizio; Massari, Leo; Cadossi, Matteo

    2013-08-01

    Hyaline cartilage lesions represent an important global health problem. Several approaches have been developed in the last decades to resolve this disability cause, including tissue engineering, but to date, there is not a definitive procedure that is able to promote a repair tissue with the same mechanical and functional characteristics of native cartilage, and to obtain its integration in the subchondral bone. The need of resolutive technologies to obtain a "more effective" tissue substitutes has led Butler to propose the "Functional Tissue Engineering" (FTE) paradigm, whose principles are outlined in a so-called FTE road map. It consists of a two-phase strategy: in vitro tissue engineering and clinically surgery evaluation. The first phase, based on construct development, should take into account not only the chondrocyte biology, as their sensitivity to biochemical and physical stimuli, the risk of dedifferentiation in culture, and the ability to produce extracellular matrix, but also the features of suitable scaffolds. The in vivo phase analyzes the inflammatory microenvironment where the construct will be placed, because the cytokines released by synoviocytes and chondrocytes could affect the construct integrity, and, in particular, cause matrix degradation. The use of pulsed electromagnetic fields (PEMFs) represents an innovative therapeutic approach, because it is demonstrated that this physical stimulus increases the anabolic activity of chondrocytes and cartilage explants with consequent increase of matrix synthesis, but, at the same time, PEMFs limit the catabolic effects of inflammatory cytokines, reducing the construct degradation inside the surgical microenvironment. PEMFs mediate an up-regulation of A2A adenosine receptors and a potentiation of their anti-inflammatory effects.

  16. Cryopreservation of articular cartilage. Part 3: the liquidus-tracking method.

    PubMed

    Pegg, David E; Wang, Lihong; Vaughan, David

    2006-06-01

    Although it is relatively straightforward to cryopreserve living isolated chondrocytes, at the present time there is no satisfactory method to preserve surgical grafts between the time of procurement or manufacture and actual use. In earlier papers we have established that the cryoprotectants dimethyl sulphoxide or propylene glycol do penetrate into this tissue very rapidly. Chondrocytes are not unusually susceptible to osmotic stress; in fact they appear to be particularly resistant. It appears that damage is associated with the formation of ice per se, even at cooling rates that are optimal for the cryopreservation of isolated chondrocytes. We then showed that current methods of cartilage cryopreservation involve the nucleation and growth of ice crystals within the chondrons rather than ice being restricted to the surrounding acellular matrix. This finding established the need to avoid the crystallization of ice--in other words, vitrification. Song and his colleagues have published a vitrification method that is based on the use of one of Fahy's vitrification formulations. We confirmed the effectiveness of this method but found it to be very dependent on ultra rapid warming. However, we were able to develop a 'liquidus-tracking' method that completely avoids the crystallization of ice and does not require rapid warming. The ability of cartilage preserved in this way to incorporate sulphate into newly synthesized glycosaminoglycans (GAGs) approached 70% of that of fresh control cartilage. In this method the rates of cooling and warming can be very low, which is essential for any method that is to be used in Tissue Banks to process the bulky grafts that are required by orthopaedic surgeons. Work is continuing to refine this method for Tissue Bank use.

  17. Treatment of articular cartilage lesions of the knee joint using a modified AMIC technique.

    PubMed

    Pascarella, Antonio; Ciatti, Riccardo; Pascarella, Fabio; Latte, Carmine; Di Salvatore, Mariano Giuseppe; Liguori, Luciano; Iannella, Germano

    2010-04-01

    This study describes a modified AMIC technique consisting of perforations according to Pridie, rather than microfractures, and the covering of the focus of the lesion with a biological collagen patch enriched with bone marrow blood drawn through the knee itself. This technique allows advantages of both the Pridie technique and the in situ proliferation of mesenchymal cells beneath a biological collagen membrane, 'augmented', with bone marrow blood. The collagen membrane forms the roof of a 'biological chamber', and serves to protect and contains the stem cells as they differentiate into chondrocytes, which will form a healthy regenerative cartilage.

  18. Chitosan/poly(vinyl alcohol) hydrogel combined with Ad-hTGF-β1 transfected mesenchymal stem cells to repair rabbit articular cartilage defects.

    PubMed

    Qi, Bai-wen; Yu, Ai-xi; Zhu, Shao-bo; Zhou, Min; Wu, Gang

    2013-01-01

    The aim of this work is to explore the feasibility and therapeutic effect of repairing rabbit articular cartilage defects using thermo-sensitive chitosan/poly (vinyl alcohol) composite hydrogel engineered Ad-hTGF-β1-transfected bone marrow mesenchymal stem cells. Rabbit's bone marrow stromal cells (BMSCs) were obtained and cultured in vitro and transfected with a well-constructed Ad-hTGF-β1 vector, the cartilage phenotype of the transfected cells was tested by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. Twenty-four New Zealand white rabbits with articular cartilage defects were randomly divided into four groups: group A was treated with CS/PVA gel and transfected BMSCs; group B received CS/PVA gel and un-transfected BMSCs; group C was treated with CS/PVA gel alone and group D was the untreated control group. Experimental animals of each group were killed at 16 weeks after operation. General observation, Masson's trichrome staining and collagen II immunohistological staining of the specimens were performed to evaluate the repair effect. The Wakitani scoring method was used to evaluate the repair effect. RT-PCR and Western blot confirmed that the hTGF-β1 gene was expressed in BMSCs and triggered the expression of specific markers of cartilage differentiation such as aggrecan mRNA and Collagen II in BMSCs after transfection with Ad-hTGF-β1. Sixteen weeks after operation, the defects in group A had smooth and flat surfaces, and the defects appeared to have completely healed, exhibiting almost the same color and texture as the surrounding cartilage. Masson's trichrome staining showed that the cell arrangement and density of regenerated cartilage tissue in group A was not significantly different from that of normal cartilage tissue. The immunohistochemical staining of Col II showed a strong expression in group A and weak expression in group B, but no expression in groups C and D. According to the Wakitani score, the difference between

  19. MRI T1ρ and T2 mapping for the assessment of articular cartilage changes in patients with medial knee osteoarthritis after hemicallotasis osteotomy

    PubMed Central

    Nakamura, E.; Hirose, J.; Okamoto, N.; Yamabe, S.; Mizuta, H.

    2016-01-01

    Objectives The purpose of this study was to clarify the appearance of the reparative tissue on the articular surface and to analyse the properties of the reparative tissue after hemicallotasis osteotomy (HCO) using MRI T1ρ and T2 mapping. Methods Coronal T1ρ an