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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. Management of knee articular cartilage injuries in athletes: chondroprotection, chondrofacilitation, and resurfacing.

    PubMed

    Murray, Iain R; Benke, Michael T; Mandelbaum, Bert R

    2016-05-01

    Articular cartilage defects of the knee are common among athletes where the physical demands of sport result in significant stresses on joints. Chondral defects are associated with pain and functional impairment that limit sporting participation and may progress to joint degeneration and frank arthritis. Management of established chondral lesions aims to allow athletes to return to high-impact sports and can be considered in terms of protection of existing cartilage, chondrofacilitation, and resurfacing. Repaired and regenerated cartilage must closely resemble and function like normal hyaline cartilage, and this ability may be the most significant factor for the return to sport. Based on our experiences and the available literature, we outline how athletes can best protect their cartilage, how physicians can facilitate intrinsic repair of established lesions, and which methods of cartilage restoration or resurfacing should be used in different situations. IV.

  3. 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

  4. Towards Regeneration of Articular Cartilage

    PubMed Central

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

    2014-01-01

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

  5. Engineering Lubrication in Articular Cartilage

    PubMed Central

    McNary, Sean M.; Athanasiou, Kyriacos A.

    2012-01-01

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

  6. Engineering lubrication in articular cartilage.

    PubMed

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

    2012-04-01

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

  7. Tensorial electrokinetics in articular cartilage.

    PubMed

    Reynaud, Boris; Quinn, Thomas M

    2006-09-15

    Electrokinetic phenomena contribute to biomechanical functions of articular cartilage and underlie promising methods for early detection of osteoarthritic lesions. Although some transport properties, such as hydraulic permeability, are known to become anisotropic with compression, the direction-dependence of cartilage electrokinetic properties remains unknown. Electroosmosis experiments were therefore performed on adult bovine articular cartilage samples, whereby fluid flows were driven by electric currents in directions parallel and perpendicular to the articular surface of statically compressed explants. Magnitudes of electrokinetic coefficients decreased slightly with compression (from approximately -7.5 microL/As in the range of 0-20% compression to -6.0 microL/As in the 35-50% range) consistent with predictions of microstructure-based models of cartilage material properties. However, no significant dependence on direction of the electrokinetic coupling coefficient was detected, even for conditions where the hydraulic permeability tensor is known to be anisotropic. This contrast may also be interpreted using microstructure-based models, and provides insights into structure-function relationships in cartilage extracellular matrix and physical mediators of cell responses to tissue compression. Findings support the use of relatively simple isotropic modeling approaches for electrokinetic phenomena in cartilage and related materials, and indicate that measurement of electrokinetic properties may provide particularly robust means for clinical evaluation of cartilage matrix integrity.

  8. 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

  9. 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.

  10. Resident mesenchymal progenitors of articular cartilage.

    PubMed

    Candela, Maria Elena; Yasuhara, Rika; Iwamoto, Masahiro; Enomoto-Iwamoto, Motomi

    2014-10-01

    Articular cartilage has poor capacity of self-renewal and repair. Insufficient number and activity of resident mesenchymal (connective tissue) progenitors is likely one of the underlying reasons. Chondroprogenitors reside not only in the superficial zone of articular cartilage but also in other zones of articular cartilage and in the neighboring tissues, including perichondrium (groove of Ranvier), synovium and fat pad. These cells may respond to injury and contribute to articular cartilage healing. In addition, marrow stromal cells can migrate through subchondral bone when articular cartilage is damaged. We should develop drugs and methods that correctly stimulate resident progenitors for improvement of repair and inhibition of degenerative changes in articular cartilage. Copyright © 2014. Published by Elsevier B.V.

  11. 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.

  12. 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

  13. 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

  14. Mechanobiological implications of articular cartilage crystals.

    PubMed

    Carlson, Alyssa K; McCutchen, Carley N; June, Ronald K

    2017-03-01

    Calcium crystals exist in both pathological and normal articular cartilage. The prevalence of these crystals dramatically increases with age, and crystals are typically found in osteoarthritic cartilage and synovial fluid. Relatively few studies have examined the effects of crystals on cartilage biomechanics or chondrocyte mechanotransduction. The purpose of this review is to describe how crystals could influence cartilage biomechanics and mechanotransduction in osteoarthritis. Crystals are found in both loaded and unloaded regions of articular cartilage. Exogenous crystals, in combination with joint motion, result in substantial joint inflammation. Articular cartilage vesicles promote crystal formation, and these vesicles are found near the periphery of chondrocytes. Crystallographic studies report monoclinic symmetry for synthetic crystals, suggesting that crystals will have a large stiffness compared with the cartilage extracellular matrix, the pericellular matrix, or the chondrocyte. This stiffness imbalance may cause crystal-induced dysregulation of chondrocyte mechanotransduction promoting both aging and osteoarthritis chondrocyte phenotypes. Because of their high stiffness compared with cartilage matrix, crystals likely alter chondrocyte mechanotransduction, and high concentrations of crystals within cartilage may alter macroscale biomechanics. Future studies should focus on understanding the mechanical properties of joint crystals and developing methods to understand how crystals affect chondrocyte mechanotransduction.

  15. 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.

  16. [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.

  17. 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.

  18. Equine Models of Articular Cartilage Repair

    PubMed Central

    McIlwraith, C. Wayne; Fortier, Lisa A.; Frisbie, David D.; Nixon, Alan J.

    2011-01-01

    Articular cartilage injuries of the knee and ankle are common, and a number of different methods have been developed in an attempt to improve their repair. Clinically, there are 2 distinct aims of cartilage repair: 1) restoration of joint function and 2) prevention or at least delay of the onset of osteoarthritis. These goals can potentially be achieved through replacement of damaged or lost articular cartilage with tissue capable of functioning under normal physiological environments for an extended period, but limitations of the final repair product have long been recognized and still exist today. Screening of potential procedures for human clinical use is done by preclinical studies using animal models. This article reviews equine chondral defect models that have been recently recognized to have specific advantages for translation into human articular cartilage regeneration. Defect models in the femoropatellar, femorotibial, and tibiotalar joints have been developed. The horse provides the closest approximation to humans in terms of articular cartilage and subchondral bone thickness, and it is possible to selectively leave the entire calcified cartilage layer or completely remove it. The defect on the equine medial femoral condyle emulates medial femoral condylar lesions in humans. Other advantages of the equine model include an ability to use an arthroscope to create lesions and perform second-look arthroscopies, the large lesion size allowing for more tissue for evaluation, and the ability to have controlled exercise and test the ability of the repair to cope with athletic exercise as well as institute rehabilitation regimens. PMID:26069590

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

    PubMed

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

    2015-01-01

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

  20. 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

  1. 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.

  2. 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

  3. [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.

  4. 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.

  5. 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.

  6. 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

  7. [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.

  8. 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.

  9. Autophagy Modulates Articular Cartilage Vesicle Formation in Primary Articular Chondrocytes*

    PubMed Central

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

    2015-01-01

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

  10. 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

  11. Quasi-linear viscoelastic properties of normal articular cartilage.

    PubMed

    Woo, S L; Simon, B R; Kuei, S C; Akeson, W H

    1980-05-01

    A combined experimental and analytical approach was used to determine the history-dependent viscoelastic properties of normal articular cartilage in tension. Specimens along the surface split line direction, taken from the middle zone of articular cartilage were subjected to relaxation and cyclic tests. A quasi-linear viscoelastic theory proposed by Fung was used in combination with the experimental results to determine the nonlinear viscoelastic properties and the elastic stress-strain relationship of normal articular cartilage.

  12. Phosphorylation of proteoglycans from human articular cartilage

    SciTech Connect

    Anderson, R.S.; Schwartz, E.R.

    1984-01-01

    Previous studies have shown that sulfated proteoglycans from human articular and epiphyseal cartilage were phosphorylated. These macromolecules contribute to the stiffness and resiliency of this tissue. We demonstrate here that the phosphate moieties are an integral part of proteoglycan subunits. Specifically, evidence is presented which indicates that proteoglycan monomers contain 3 to 4 phosphate moieties per core protein and that these appear to exist as phosphoserine residues. Furthermore, the data illustrate that human articular cartilage also contains more than 20 different phosphoproteins, some of which are closely associated with proteoglycan aggregates. Proteoglycan subunits were purified from extracts of articular cartilage or from media fractions which had been used to label tissue specimens with 32P-orthophosphate. Chemical and radiographic analyses revealed that the phosphate concentration with respect to sulfate and uronic acid content remained constant when purified proteoglycan monomers were subjected to equilibrium ultracentrifugation and size-exclusion chromatography. That the phosphate moieties were bound to proteoglycan monomers via monoester linkages was indicated by the release of 32P-orthophosphate from proteoglycan subunits incubated under mild alkaline conditions or reacted with acid or alkaline phosphatases. Identification of serine residues in the core protein as the sites of phosphorylation was made by autoradiography of thin layer plates on which hydrolyzed samples of purified 32P-proteoglycan subunits had been subjected to 2-dimensional electrophoresis/chromatography. Quantification of 3 to 4 phosphate moieties per core protein of 200,000 daltons was made by chemical analysis of inorganic phosphate released from proteoglycans by acid hydrolysis.

  13. 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

  14. 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

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

    PubMed

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

    2014-05-05

    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.

  16. 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

  17. 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

  18. [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.

  19. 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

  20. Blends and Nanocomposite Biomaterials for Articular Cartilage Tissue Engineering

    PubMed Central

    Doulabi, Azadehsadat Hashemi; Mequanint, Kibret; Mohammadi, Hadi

    2014-01-01

    This review provides a comprehensive assessment on polymer blends and nanocomposite systems for articular cartilage tissue engineering applications. Classification of various types of blends including natural/natural, synthetic/synthetic systems, their combination and nanocomposite biomaterials are studied. Additionally, an inclusive study on their characteristics, cell responses ability to mimic tissue and regenerate damaged articular cartilage with respect to have functionality and composition needed for native tissue, are also provided. PMID:28788131

  1. Articular cartilage tissue engineering: the role of signaling molecules

    PubMed Central

    Kwon, Heenam; Paschos, Nikolaos K.; Hu, Jerry C.; Athanasiou, Kyriacos

    2017-01-01

    Effective early disease modifying options for osteoarthritis remain lacking. Tissue engineering approach to generate cartilage in vitro has emerged as a promising option for articular cartilage repair and regeneration. Signaling molecules and matrix modifying agents, derived from knowledge of cartilage development and homeostasis, have been used as biochemical stimuli toward cartilage tissue engineering and have led to improvements in the functionality of engineered cartilage. Clinical translation of neocartilage faces challenges, such as phenotypic instability of the engineered cartilage, poor integration, inflammation, and catabolic factors in the arthritic environment; these can all contribute to failure of implanted neocartilage. A comprehensive understanding of signaling molecules involved in osteoarthritis pathogenesis and their actions on engineered cartilage will be crucial. Thus, while it is important to continue deriving inspiration from cartilage development and homeostasis, it has become increasing necessary to incorporate knowledge from osteoarthritis pathogenesis into cartilage tissue engineering. PMID:26811234

  2. Articular cartilage tissue engineering: the role of signaling molecules.

    PubMed

    Kwon, Heenam; Paschos, Nikolaos K; Hu, Jerry C; Athanasiou, Kyriacos

    2016-03-01

    Effective early disease modifying options for osteoarthritis remain lacking. Tissue engineering approach to generate cartilage in vitro has emerged as a promising option for articular cartilage repair and regeneration. Signaling molecules and matrix modifying agents, derived from knowledge of cartilage development and homeostasis, have been used as biochemical stimuli toward cartilage tissue engineering and have led to improvements in the functionality of engineered cartilage. Clinical translation of neocartilage faces challenges, such as phenotypic instability of the engineered cartilage, poor integration, inflammation, and catabolic factors in the arthritic environment; these can all contribute to failure of implanted neocartilage. A comprehensive understanding of signaling molecules involved in osteoarthritis pathogenesis and their actions on engineered cartilage will be crucial. Thus, while it is important to continue deriving inspiration from cartilage development and homeostasis, it has become increasingly necessary to incorporate knowledge from osteoarthritis pathogenesis into cartilage tissue engineering.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. Vitamin D and Its Effects on Articular Cartilage and Osteoarthritis.

    PubMed

    Garfinkel, Rachel J; Dilisio, Matthew F; Agrawal, Devendra K

    2017-06-01

    Osteoarthritis (OA) currently affects 10% of the American population. There has been a recent push to determine exactly what causes OA and how it can be treated most effectively. Serum vitamin D levels have been associated with OA and may have an effect on articular cartilage remodeling. To critically review the published research on the effect of vitamin D on articular cartilage and the development of OA as well as on the mechanism behind cartilage regeneration and degeneration. Review. A systematic search of PubMed and the Web of Science was performed for relevant studies published in the English language through April 30, 2016, using the terms vitamin D, articular cartilage, and osteoarthritis. On a molecular level, 1α,25(OH)2D3, the activated form of vitamin D, plays a role in articular cartilage degeneration. Vitamin D binds to vitamin D receptors, triggering a signaling cascade that leads to chondrocyte hypertrophy. In clinical trials, vitamin D deficiency poses a risk factor for OA, and those with decreased cartilage thickness are more likely to be vitamin D-insufficient. The role of vitamin D supplementation in the treatment or prevention of OA remains uncertain. More research is needed to reconcile these conflicting findings.

  9. Computational aspects in mechanical modeling of the articular cartilage tissue.

    PubMed

    Mohammadi, Hadi; Mequanint, Kibret; Herzog, Walter

    2013-04-01

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

  10. Biphasic surface amorphous layer lubrication of articular cartilage.

    PubMed

    Graindorge, Simon; Ferrandez, Wendy; Jin, Zhongmin; Ingham, Eileen; Grant, Colin; Twigg, Peter; Fisher, John

    2005-12-01

    The biphasic nature of articular cartilage has been acknowledged for some time and is known to play an important role in many of the biomechanical functions performed by this unique tissue. From the lubrication point of view however, a simple biphasic model is unable to account for the extremely low friction coefficients that have been recorded experimentally, particularly during start-up. In addition, research over the last decade has indicated the presence of a surface amorphous layer on top of articular cartilage. Here, we present results from a finite element model of articular cartilage that includes a thin, soft, biphasic surface amorphous layer (BSAL). The results of this study show that a thin BSAL, with lower elastic modulus, dramatically altered the load sharing between the solid and liquid phases of articular cartilage, particularly in the near-surface regions of the underlying bulk cartilage and within the surface amorphous layer itself where the fluid load support exceeded 85%. By transferring the load from the solid phase to the fluid phase, the biphasic surface layer improves lubrication and reduces friction, whilst also protecting the underlying cartilage surface by 'shielding' the solid phase from elevated stresses. The increase in lubrication effectiveness is shown to be greatest during short duration loading scenarios, such as shock loads.

  11. 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.

  12. Nonuniform swelling-induced residual strains in articular cartilage.

    PubMed

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

    1999-04-01

    Swelling effects in cartilage originate from an interstitial osmotic pressure generated by the presence of negatively charged proteoglycans in the tissue. This swelling pressure gives rise to a non-zero residual strain in the cartilage solid matrix in the absence of externally applied loads. Previous studies have quantified swelling effects in cartilage as volumetric or dimensional change of excised samples in varying osmotically active solutions. This study presents a new optical technique for measuring two-dimensional swelling-induced residual strain fields in planar samples of articular cartilage attached to the bone (i.e., in situ). Osmotic loading was applied to canine cartilage bone samples by equilibration in external baths of varying NaCl concentration. Non-zero swelling-induced strains were measured in physiological saline, giving evidence of the existence of residual strains in articular cartilage. Only one component of planar strain (i.e., in thickness direction) was found to be non-zero. This strain was found to be highly non-uniform in the thickness direction, with evidence of compressive strain in the deep zone of cartilage and tensile strain in the middle and surface zones. The obtained results can be used to characterize the material properties of the articular cartilage solid matrix, with estimated values of 26 M Pa for the tensile modulus for middle zone cartilage. The method provides the basis to obtain material properties of the cartilage solid matrix from a simple, free-swelling test and may be useful for quantifying changes in cartilage properties with injury, degeneration and repair.

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

    PubMed

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

    2013-09-01

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

  14. Brother of CDO (BOC) expression in equine articular cartilage.

    PubMed

    Vanderman, K S; Tremblay, M; Zhu, W; Shimojo, M; Mienaltowski, M J; Coleman, S J; MacLeod, J N

    2011-04-01

    Brother of CDO (BOC) is a cell surface receptor that derives its name from the structurally related protein, cell adhesion molecule-related/down-regulated by oncogenes (CDO, sometimes CDON). High levels of BOC mRNA and protein expression have been described in embryonic tissues with active cell proliferation and ongoing cellular differentiation(1,2). A microarray-based screen of RNA isolated from 11 different adult equine tissues unexpectedly identified BOC as having an expression pattern restricted to articular cartilage. The objective of this study was to further investigate BOC expression in adult articular cartilage relative to other tissues. Both RT-qPCR and mRNA sequencing confirmed the microarray data. Steady state BOC mRNA levels in articular cartilage were substantially higher than in the other adult tissues tested, neonatal tendon, placenta, and whole embryo. The expression of BOC displayed a pattern of tissue specificity comparable to well established cartilage matrix protein biomarkers. BOC mRNA levels in articular cartilage increased with age, but were rapidly down-regulated when chondrocytes were enzymatically isolated from the cartilage matrix and expanded in monolayer culture. Relative expression patterns of CDO were broadly similar, but displayed lower fold change differences. A functional role in articular cartilage that involves Hedgehog signaling is suggested by the known binding affinity of BOC for all three Hedgehog ligands. These data also extend BOC and CDO biology to a post-mitotic and highly differentiated cell type within a mature tissue. Copyright © 2011 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  15. 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.

  16. Surface fissures in articular cartilage: new concepts, hypotheses and modeling.

    PubMed

    Kafka, Vratislav

    2002-01-01

    Clarification and mesomechanical modeling of the inception of fissures at the surface of articular cartilage. Articular cartilage is described as a macroscopically heterogeneous medium consisting of zones - layers - with different orientation of collagen fibers. Degradation of mechanical properties of cartilage is a serious, still not fully clarified problem that deserves attention. Theoretical analysis based on a survey of known experimental findings related to the subject. The general author's mesomechanical concept of modeling heterogeneous media is applied to the elucidation and description of the formation of fissures at the surface of articular cartilage. Our model clarifies how the high tensile stresses in the collagen fibers of the superficial tangential zone depend on the rate of loading. The superficial cracks are caused predominantly by a very quick loading. This explains among others the high incidence of post-traumatic osteoarthritis of the lower extremity after accidents and injuries in sports. Superficial fissures in articular cartilage are observed in joints with primary osteoarthritis. The current study specifies the kinds of loading that lead to their inception.

  17. 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.

  18. 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. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. 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

  20. Hydrogels as a Replacement Material for Damaged Articular Hyaline Cartilage.

    PubMed

    Beddoes, Charlotte M; Whitehouse, Michael R; Briscoe, Wuge H; Su, Bo

    2016-06-03

    Hyaline cartilage is a strong durable material that lubricates joint movement. Due to its avascular structure, cartilage has a poor self-healing ability, thus, a challenge in joint recovery. When severely damaged, cartilage may need to be replaced. However, currently we are unable to replicate the hyaline cartilage, and as such, alternative materials with considerably different properties are used. This results in undesirable side effects, including inadequate lubrication, wear debris, wear of the opposing articular cartilage, and weakening of the surrounding tissue. With the number of surgeries for cartilage repair increasing, a need for materials that can better mimic cartilage, and support the surrounding material in its typical function, is becoming evident. Here, we present a brief overview of the structure and properties of the hyaline cartilage and the current methods for cartilage repair. We then highlight some of the alternative materials under development as potential methods of repair; this is followed by an overview of the development of tough hydrogels. In particular, double network (DN) hydrogels are a promising replacement material, with continually improving physical properties. These hydrogels are coming closer to replicating the strength and toughness of the hyaline cartilage, while offering excellent lubrication. We conclude by highlighting several different methods of integrating replacement materials with the native joint to ensure stability and optimal behaviour.

  1. Hydrogels as a Replacement Material for Damaged Articular Hyaline Cartilage

    PubMed Central

    Beddoes, Charlotte M.; Whitehouse, Michael R.; Briscoe, Wuge H.; Su, Bo

    2016-01-01

    Hyaline cartilage is a strong durable material that lubricates joint movement. Due to its avascular structure, cartilage has a poor self-healing ability, thus, a challenge in joint recovery. When severely damaged, cartilage may need to be replaced. However, currently we are unable to replicate the hyaline cartilage, and as such, alternative materials with considerably different properties are used. This results in undesirable side effects, including inadequate lubrication, wear debris, wear of the opposing articular cartilage, and weakening of the surrounding tissue. With the number of surgeries for cartilage repair increasing, a need for materials that can better mimic cartilage, and support the surrounding material in its typical function, is becoming evident. Here, we present a brief overview of the structure and properties of the hyaline cartilage and the current methods for cartilage repair. We then highlight some of the alternative materials under development as potential methods of repair; this is followed by an overview of the development of tough hydrogels. In particular, double network (DN) hydrogels are a promising replacement material, with continually improving physical properties. These hydrogels are coming closer to replicating the strength and toughness of the hyaline cartilage, while offering excellent lubrication. We conclude by highlighting several different methods of integrating replacement materials with the native joint to ensure stability and optimal behaviour. PMID:28773566

  2. Inorganic phosphate transport in matrix vesicles from bovine articular cartilage.

    PubMed

    Solomon, D H; Browning, J A; Wilkins, R J

    2007-06-01

    In mineralizing tissues such as growth plate cartilage extracellular organelles derived from the chondrocyte membrane are present. These matrix vesicles (MV), possess membrane transporters that accumulate Ca(2+) and inorganic phosphate (P(i)), and initiate the formation of hydroxyapatite crystals. MV are also present in articular cartilage, and hydroxyapatite crystals are believed to promote cartilage degradation in osteoarthritic joints. This study characterizes P(i) transport in MV derived from articular cartilage. Matrix vesicles were harvested from collagenase digests of bovine articular cartilage by serial centrifugation. P(i) uptake by MV was measured using radioactive phosphate ((33)[P]HPO(4)(2-)). The Na(+) dependence, pH sensitivity and effects of P(i) analogues that inhibit P(i) transport were determined. P(i) uptake was temperature-sensitive and comprised Na(+)-dependent and Na(+)-independent components. The Na(+)-dependent component saturated at high extracellular P(i) concentrations, with a K(m) of 0.16 mM. In Na(+)-free solutions, uptake did not fully saturate implying that carrier-mediated uptake is supplemented by a diffusive pathway. Uptake was inhibited by phosphonoacetate and arsenate, although a fraction of Na(+)-independent P(i) uptake persisted. Total P(i) uptake was maximal at pH 6.5, and reduced at more acidic or alkaline values, representing inhibition of both components. These properties are highly similar to those of P(i) uptake by chondrocytes, suggesting that MV inherit P(i) transporters of the chondrocyte membrane from which they are derived. Na(+)-independent P(i) uptake has not previously been described in MV from growth plate cartilage and is relatively uncharacterized, but warrants further attention in articular cartilage, given its likely role in initiating inappropriate mineral formation.

  3. Combinatorial scaffold morphologies for zonal articular cartilage engineering☆

    PubMed Central

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

    2014-01-01

    Articular cartilage lesions are a particular challenge for regenerative medicine strategies as cartilage function stems from a complex depth-dependent organization. Tissue engineering scaffolds that vary in morphology and function offer a template for zone-specific cartilage extracellular matrix (ECM) production and mechanical properties. We fabricated multi-zone cartilage scaffolds by the electrostatic deposition of polymer microfibres onto particulate-templated scaffolds produced with 0.03 or 1.0 mm3 porogens. The scaffolds allowed ample space for chondrocyte ECM production within the bulk while also mimicking the structural organization and functional interface of cartilage’s superficial zone. Addition of aligned fibre membranes enhanced the mechanical and surface properties of particulate-templated scaffolds. Zonal analysis of scaffolds demonstrated region-specific variations in chondrocyte number, sulfated GAG-rich ECM, and chondrocytic gene expression. Specifically, smaller porogens (0.03 mm3) yielded significantly higher sGAG accumulation and aggrecan gene expression. Our results demonstrate that bilayered scaffolds mimic some key structural characteristics of native cartilage, support in vitro cartilage formation, and have superior features to homogeneous particulate-templated scaffolds. We propose that these scaffolds offer promise for regenerative medicine strategies to repair articular cartilage lesions. PMID:24370641

  4. 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.

  5. 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.

  6. Treatment of articular cartilage lesions of the knee

    PubMed Central

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

    2010-01-01

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

  7. 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

  8. 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.

  9. 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.

  10. 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

  11. Hydrogels for the Repair of Articular Cartilage Defects

    PubMed Central

    Maher, Suzanne A.; Lowman, Anthony M.

    2011-01-01

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

  12. Segmenting articular cartilage automatically using a voxel classification approach.

    PubMed

    Folkesson, Jenny; Dam, Erik B; Olsen, Ole F; Pettersen, Paola C; Christiansen, Claus

    2007-01-01

    We present a fully automatic method for articular cartilage segmentation from magnetic resonance imaging (MRI) which we use as the foundation of a quantitative cartilage assessment. We evaluate our method by comparisons to manual segmentations by a radiologist and by examining the interscan reproducibility of the volume and area estimates. Training and evaluation of the method is performed on a data set consisting of 139 scans of knees with a status ranging from healthy to severely osteoarthritic. This is, to our knowledge, the only fully automatic cartilage segmentation method that has good agreement with manual segmentations, an interscan reproducibility as good as that of a human expert, and enables the separation between healthy and osteoarthritic populations. While high-field scanners offer high-quality imaging from which the articular cartilage have been evaluated extensively using manual and automated image analysis techniques, low-field scanners on the other hand produce lower quality images but to a fraction of the cost of their high-field counterpart. For low-field MRI, there is no well-established accuracy validation for quantitative cartilage estimates, but we show that differences between healthy and osteoarthritic populations are statistically significant using our cartilage volume and surface area estimates, which suggests that low-field MRI analysis can become a useful, affordable tool in clinical studies.

  13. Changes in articular cartilage in experimentally induced patellar subluxation

    PubMed Central

    Ryu, J.; Saito, S.; Yamamoto, K.

    1997-01-01

    OBJECTIVES—Patellar subluxation was experimentally induced in young rabbits and the resulting cartilaginous changes were observed over a prolonged period of time to determine histological changes in the subluxated patellar cartilage.
METHODS—The tibial tuberosity in 12 week old rabbits was laterally displaced and fixed to the tibia with wire to induce lateral patellar subluxation. Pathological changes in patellar cartilage were examined for 120 weeks after surgery using computed tomography and stereoscopic microscopy.
RESULTS—Eight weeks after surgery, changes in articular cartilage consisting of horizontal splitting of the matrix were observed in the intermediate zone and were presumed to have been caused by shearing stress applied to the patellar cartilage. The cartilaginous changes caused by patellar subluxation progressed very little over the 120 weeks. Very few rabbits presented with osteoarthritic changes in the patellofemoral joint, most probably because the stress resulting from the malalignment of the patellofemoral joint was mild enough to permit recovery.
CONCLUSION—The mild, non-progressive pathological changes, in particular, basal degeneration, induced in this experiment in patellar cartilage were quite similar to the changes in articular cartilage seen in human chondromalacia patellae.

 PMID:9462171

  14. 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.

  15. The biochemical content of articular cartilage: an original MRI approach.

    PubMed

    Loeuille, Damien; Olivier, Pierre; Watrin, Astrid; Grossin, Laurent; Gonord, Patrick; Guillot, Geneviève; Etienne, Stéphanie; Blum, Alain; Netter, Patrick; Gillet, Pierre

    2002-01-01

    The MR aspect of articular cartilage, that reflects the interactions between protons and macromolecular constituents, is affected by the intrinsic tissue structure (water content, the content of matrix constituents, collagen network organization), imager characteristics, and acquisition parameters. On the T1-weighted sequences, the bovine articular cartilage appears as an homogeneous tissue in high signal intensity, whatever the age of animals considered, whereas on the T2-weighted sequences, the articular bovine cartilage presents variations of its imaging pattern (laminar appearance) well correlated to the variations of its histological and biochemical structure. The T2 relaxation time measurement (T2 mapping), which reflects quantitatively the signal intensity variations observed on T2 weighted sequences, is a way to evaluate more precisely the modifications of cartilage structure during the aging and maturation processes (rat's study). This technique so far confined to experimental micro-imagers is now developed on clinical imagers. Consequently, it may permit to depict the early stages of osteoarthritic disease (OA) or to evaluate the chondroprotective effect of drugs.

  16. Rolling resistance of articular cartilage due to interstitial fluid flow.

    PubMed

    Ateshian, G A; Wang, H

    1997-01-01

    A mechanism which may contribute to the frictional coefficient of diarthrodial joints is the rolling resistance due to hysteretic energy loss of viscoelastic cartilage resulting from interstitial fluid flow. The hypothesis of this study is that rolling resistance contributes significantly to the measured friction coefficient of articular cartilage. Due to the difficulty of testing this hypothesis experimentally, theoretical predictions of the rolling resistance are obtained using the solution for rolling contact of biphasic cylindrical cartilage layers [Ateshian and Wang]. Over a range of rolling velocities, tissue properties and dimensions, it is found that the coefficient of rolling resistance microR varies in magnitude from 10(-6) to 10(-2); thus, it is generally negligible in comparison with experimental measurements of the cartilage friction coefficient (10(-3)-10(-1)) except, possibly, when the tissue is arthritic. Hence, the hypothesis of this study is rejected on the basis of these results.

  17. Chondroitin sulfate reduces the friction coefficient of articular cartilage.

    PubMed

    Basalo, Ines M; Chahine, Nadeen O; Kaplun, Michael; Chen, Faye H; Hung, Clark T; Ateshian, Gerard A

    2007-01-01

    The objective of this study was to investigate the effect of chondroitin sulfate (CS)-C on the frictional response of bovine articular cartilage. The main hypothesis is that CS decreases the friction coefficient of articular cartilage. Corollary hypotheses are that viscosity and osmotic pressure are not the mechanisms that mediate the reduction in the friction coefficient by CS. In Experiment 1, bovine articular cartilage samples (n=29) were tested in either phosphate buffered saline (PBS) or in PBS containing 100mg/ml of CS following 48h incubation in PBS or in PBS+100mg/ml CS (control specimens were not subjected to any incubation). In Experiment 2, samples (n=23) were tested in four different solutions: PBS, PBS+100mg/ml CS, and PBS+polyethylene glycol (PEG) (133 or 170mg/ml). In Experiment 3, samples (n=18) were tested in three solutions of CS (0, 10 and 100mg/ml). Frictional tests (cartilage-on-glass) were performed under constant stress (0.5MPa) for 3600s and the time-dependent friction coefficient was measured. Samples incubated or tested in a 100mg/ml CS solution exhibited a significantly lower equilibrium friction coefficient than the respective PBS control. PEG solutions delayed the rise in the friction coefficient relative to the PBS control, but did not reduce the equilibrium value. Testing in PBS+10mg/ml of CS did not cause any significant decrease in the friction coefficient. In conclusion, CS at a concentration of 100mg/ml significantly reduces the friction coefficient of bovine articular cartilage and this mechanism is neither mediated by viscosity nor osmolarity. These results suggest that direct injection of CS into the joint may provide beneficial tribological effects.

  18. 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.

  19. 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

  20. 3D braid scaffolds for regeneration of articular cartilage.

    PubMed

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

    2014-06-01

    Regenerating articular cartilage in vivo from cultured chondrocytes requires that the cells be cultured and implanted within a biocompatible, biodegradable scaffold. Such scaffolds must be mechanically stable; otherwise chondrocytes would not be supported and patients would experience severe pain. Here we report a new 3D braid scaffold that matches the anisotropic (gradient) mechanical properties of natural articular cartilage and is permissive to cell cultivation. To design an optimal structure, the scaffold unit cell was mathematically modeled and imported into finite element analysis. Based on this analysis, a 3D braid structure with gradient axial yarn distribution was designed and manufactured using a custom-built braiding machine. The mechanical properties of the 3D braid scaffold were evaluated and compared with simulated results, demonstrating that a multi-scale approach consisting of unit cell modeling and continuum analysis facilitates design of scaffolds that meet the requirements for mechanical compatibility with tissues. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Repair of articular cartilage defects: part II. Treatment options.

    PubMed

    Chen, F S; Frenkel, S R; Di Cesare, P E

    1999-02-01

    Articular cartilage injuries result in numerous clinical symptoms, such as pain and decreased functional levels. Current therapeutic options being used include articular surface debridement, such as chondral shaving, abrasion chondroplasty, and subchondral perforation; soft-tissue arthroplasties, such as perichondrial and periosteal grafts; and osteochondral transplantation. None of these therapies, however, has resulted in the successful regeneration of a hyaline-like tissue that withstands normal joint loading and activity over prolonged periods. As a result, research is also being conducted on alternative therapeutic procedures to enhance the repair process and to stimulate the regeneration of a repair tissue with hyaline-like structural and biologic properties. Part I of this paper, which was published in January, discussed the basic science of cartilage healing. Part II presents the treatment options.

  2. 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

  3. 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.

  4. 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

  5. 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

  6. Changes in articular cartilage following arthroscopic partial medial meniscectomy.

    PubMed

    Eichinger, Martin; Schocke, Michael; Hoser, Christian; Fink, Christian; Mayr, Raul; Rosenberger, Ralf E

    2016-05-01

    To examine degenerative changes in all cartilage surfaces of the knee following arthroscopic partial medial meniscectomy. For this prospective cohort study, 14 patients (five female) with a mean age of 47.9 ± 12.9 years who had undergone isolated arthroscopic partial medial meniscectomy were evaluated. Cartilage-sensitive magnetic resonance imaging (MRI) scans were acquired from the operated knees before the index operations, as well as at 6, 12, and 24 months after surgery. The MRI scans were assessed for the prevalence, severity, and size of cartilage degenerations. The clinical outcome was assessed using the SF-36 physical and mental component score and the International Knee Documentation Committee Knee Evaluation Form and was correlated with radiological findings. There was a significant increase in the severity of cartilage lesions in the medial tibial plateau (P = 0.019), as well as a trend towards an increase in the lateral tibial plateau. The size of the cartilage lesions increased significantly in the medial femoral condyle (P = 0.005) and lateral femoral condyle (P = 0.029), as well as in the patella (P = 0.019). Functional outcome scores improved significantly throughout the follow-up period. There was no correlation between cartilage wear and functional outcome. Arthroscopic partial medial meniscectomy is associated with adverse effects on articular cartilage and may lead to an increase in the severity and size of cartilage lesions. Post-operative cartilage wear predominantly affected the medial compartment and also affected the other compartments of the knee. Strategies to reduce subsequent osteoarthritic changes need to involve all compartments of the knee. IV.

  7. 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.

  8. 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

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

    PubMed

    Li, Feng; Wang, Anmin; Wang, Chengtao

    2016-05-01

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

  10. 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

  11. 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

  12. 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.

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

    PubMed

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

    2015-10-01

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

  14. Label-free characterization of degenerative changes in articular cartilage by Raman spectroscopy

    NASA Astrophysics Data System (ADS)

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

    2017-04-01

    Osteoarthritis (OA) is very common joint disease in the aging population. Main symptom of OA is accompanied by degenerative changes of articular cartilage. Raman spectroscopy is a label-free technique which enables to analyze molecular composition in degenerative cartilage. We generated an animal OA model surgically induced by knee joint instability and performed Raman spectroscopic analysis for the articular cartilage. In the result, Raman spectral data of the articular cartilage showed drastic changes in comparison between OA and control side. The relative intensity of phosphate band increases in the degenerative cartilage.

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

    PubMed Central

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

    2014-01-01

    Limb synovial joints are intricate structures composed of articular cartilage, synovial membranes, ligaments and an articular capsule. Each joint has a unique shape, organization and biomechanical function, and articular cartilage itself is rather complex and organized in distinct zones, including the superficial zone that produces lubricans and contains stem/progenitor cells. There has been a great of interest for many years to decipher 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 is the appearance of a dense and compact population of mesenchymal cells collectively called the interzone. Work carried out since by several groups has provided evidence that the interzone cells do actively participate in joint tissue formation over developmental time. This minireview provides a succinct but comprehensive description of the many and important recent advances in this field of research. These includes: 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 have major implications to conceive future translational medicine tools to repair and regenerate defective, overused or aging joints. PMID:25172830

  16. Surface fissures in articular cartilage: effect of pathological changes in synovial fluid.

    PubMed

    Kafka, Vratislav

    2002-01-01

    A unified mathematical model of two different modes of inception of fissures at the surface of articular cartilage in healthy and pathological joints. The superficial tangential zone of articular cartilage is modeled as a three-phase medium consisting of collagen fibers, matrix, and of infiltrated thin constituent of synovial fluid. The author's general mesomechanical concept is applied to the analysis of deterioration of articular cartilage. Theoretical analysis based on the results of the author's preceding paper. The presented analysis shows that superficial fissures in articular cartilage can also be caused by pathological thinning of synovial fluid. Whereas in healthy joints the probable cause of creation of fissures at the surface of cartilage was shown to be fast impact loading, in joints with inflammatory synovial fluid the fissures can be caused by plain walking. Appearance of surface fissures in articular cartilage is a serious, still not fully clarified problem that deserves attention.

  17. 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

  18. 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.

  19. 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.

  20. 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

  1. 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: )

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

    PubMed

    Zhao, Ming; Chen, Zhu; Liu, Kang; Wan, Yu-qing; Li, Xu-dong; Luo, Xu-wei; Bai, Yi-guang; Yang, Ze-long; Feng, Gang

    2015-11-01

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

  3. T2 star relaxation times for assessment of articular cartilage at 3 T: a feasibility study.

    PubMed

    Mamisch, Tallal Charles; Hughes, Timothy; Mosher, Timothy J; Mueller, Christoph; Trattnig, Siegfried; Boesch, Chris; Welsch, Goetz Hannes

    2012-03-01

    T2 mapping techniques use the relaxation constant as an indirect marker of cartilage structure, and the relaxation constant has also been shown to be a sensitive parameter for cartilage evaluation. As a possible additional robust biomarker, T2* relaxation time is a potential, clinically feasible parameter for the biochemical evaluation of articular cartilage. The knees of 15 healthy volunteers and 15 patients after microfracture therapy (MFX) were evaluated with a multi-echo spin-echo T2 mapping technique and a multi-echo gradient-echo T2* mapping sequence at 3.0 Tesla MRI. Inline maps, using a log-linear least squares fitting method, were assessed with respect to the zonal dependency of T2 and T2* relaxation for the deep and superficial regions of healthy articular cartilage and cartilage repair tissue. There was a statistically significant correlation between T2 and T2* values. Both parameters demonstrated similar spatial dependency, with longer values measured toward the articular surface for healthy articular cartilage. No spatial variation was observed for cartilage repair tissue after MFX. Within this feasibility study, both T2 and T2* relaxation parameters demonstrated a similar response in the assessment of articular cartilage and cartilage repair tissue. The potential advantages of T2*-mapping of cartilage include faster imaging times and the opportunity for 3D acquisitions, thereby providing greater spatial resolution and complete coverage of the articular surface.

  4. 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.

  5. Non-linear model for compression tests on articular cartilage.

    PubMed

    Grillo, Alfio; Guaily, Amr; Giverso, Chiara; Federico, Salvatore

    2015-07-01

    Hydrated soft tissues, such as articular cartilage, are often modeled as biphasic systems with individually incompressible solid and fluid phases, and biphasic models are employed to fit experimental data in order to determine the mechanical and hydraulic properties of the tissues. Two of the most common experimental setups are confined and unconfined compression. Analytical solutions exist for the unconfined case with the linear, isotropic, homogeneous model of articular cartilage, and for the confined case with the non-linear, isotropic, homogeneous model. The aim of this contribution is to provide an easily implementable numerical tool to determine a solution to the governing differential equations of (homogeneous and isotropic) unconfined and (inhomogeneous and isotropic) confined compression under large deformations. The large-deformation governing equations are reduced to equivalent diffusive equations, which are then solved by means of finite difference (FD) methods. The solution strategy proposed here could be used to generate benchmark tests for validating complex user-defined material models within finite element (FE) implementations, and for determining the tissue's mechanical and hydraulic properties from experimental data.

  6. 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

  7. 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

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

    NASA Astrophysics Data System (ADS)

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

    2017-02-01

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

  9. 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%).

  10. 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.

  11. 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.

  12. 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

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

    PubMed Central

    Chan, Deva D.; Neu, Corey P.

    2013-01-01

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

  14. Some conceptual thoughts toward nanoscale oriented friction in a model of articular cartilage.

    PubMed

    Gadomski, Adam; Bełdowski, Piotr; Rubì, J Miguel; Urbaniak, Wiesław; Augé, Wayne K; Santamarìa-Holek, Ivan; Pawlak, Zenon

    2013-08-01

    This work presents a conceptual framework as to how a deficit in the synovial-fluid content, exemplified by hyaluronan or any other amphiphilic species, is capable of decisively altering the complex lubrication and wear conditions observed clinically in articular cartilage. The effect is revealed in (non)stationary regimes if the cartilage is subjected to some normal periodic load, revealing over its exploitation time increasingly dissipative, in general entropy-addressing, characteristics. It can be hypothesized that a Grotthuss-type proton transport physiology-concerning mechanism in channel-like, phospholipid-water cartilage's articulating nanospaces will be responsible for the expression of the lubrication mode. The corresponding wear involving overall change is then manifested adequately in the stationary regime, and in a viable system-parametric correlation with its lubrication counterpart. Certain analytic formulae for the nanoscale oriented coefficient of friction, involving generically H-bonds breaking mechanism, and pointing to some local-viscosity context, have been proposed for fitting the experimental data and clinical observations involving proton management at articular cartilage surfaces. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. 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.

  16. Superficial Zone Extracellular Matrix Extracts Enhance Boundary Lubrication of Self-Assembled Articular Cartilage

    PubMed Central

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

    2015-01-01

    Objective Previous work has shown that increasing the production of boundary lubricant, superficial zone protein (SZP), did not reduce the friction coefficient of self-assembled articular cartilage constructs and was possibly due to poor retention of the lubricant. The aim of this investigation was to reduce the friction coefficient of self-assembled articular cartilage constructs through enhancing SZP retention by the exogenous addition of extracellular matrix (ECM) extracted from the superficial zone of native articular cartilage. Design Superficial zone cartilage was shaved from juvenile bovine femoral condyles using a dermatome, minced finely with razor blades, extracted with 4 M guanidine-hydrochloride, buffer exchanged with culture medium, and added directly to the culture medium of self-assembled articular cartilage constructs at low (10 µg/mL) and high (100 µg/mL) concentrations for 4 weeks. Biochemical and biomechanical properties were determined at the conclusion of 4 weeks culture. Results ECM treatment increased compressive and tensile stiffness of self-assembled articular cartilage constructs and decreased the friction coefficient. Glycosaminoglycan content decreased and collagen content increased significantly in self-assembled constructs by the ECM treatment. Conclusions Friction coefficients of self-assembled articular cartilage constructs were reduced by adding extracted superficial zone ECM into the culture medium of self-assembled articular cartilage constructs. PMID:27375841

  17. 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. Copyright © 2014 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

  18. 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

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. Heterotopic autologous chondrocyte transplantation--a realistic approach to support articular cartilage repair?

    PubMed

    El Sayed, Karym; Haisch, Andreas; John, Thilo; Marzahn, Ulrike; Lohan, Anke; Müller, Riccarda D; Kohl, Benjamin; Ertel, Wolfgang; Stoelzel, Katharina; Schulze-Tanzil, Gundula

    2010-12-01

    Injured articular cartilage is limited in its capacity to heal. Autologous chondrocyte transplantation (ACT) is a suitable technique for cartilage repair, but it requires articular cartilage biopsies for sufficient autologous chondrocyte expansion in vitro. Hence, ACT is restricted by donor-site morbidity and autologous articular chondrocytes availability. The use of nonarticular heterotopic chondrocytes such as auricular, nasoseptal, or costal chondrocytes for ACT might overcome these limitations: heterotopic sources show lesser donor-site morbidity and a comparable extracellular cartilage matrix synthesis profile to articular cartilage. However, heterotopic (h)ACT poses a challenge. Particular tissue characteristics of heterotopic cartilage, divergent culturing peculiarities of heterotopic chondrocytes, and the advantages and drawbacks related to these diverse cartilage sources were critically discussed. Finally, available in vitro and in vivo experimental (h)ACT approaches were summarized. The quality of the cartilage engineered using heterotopic chondrocytes remains partly controversy due to the divergent methodologies and culture conditions used. While some encouraging in vivo results using (h)ACT have been demonstrated, standardized culturing protocols are strongly required. However, whether heterotopic chondrocytes implanted into joint cartilage defects maintain their particular tissue properties or can be adapted via tissue engineering strategies to fulfill regular articular cartilage functions requires further studies.

  4. Transient anabolic effects accompany epidermal growth factor receptor signal activation in articular cartilage in vivo

    PubMed Central

    2013-01-01

    Introduction Signals from the epidermal growth factor receptor (EGFR) have typically been considered to provide catabolic activities in articular cartilage, and accordingly have been suggested to have a causal role in osteoarthritis progression. The aim of this study was to determine in vivo roles for endogenous EGFR signal activation in articular cartilage. Methods Transgenic mice with conditional, limb-targeted deletion of the endogenous intracellular EGFR inhibitor Mig-6 were generated using CreLoxP (Mig-6-flox; Prx1Cre) recombination. Histology, histochemical staining and immunohistochemistry were used to confirm activation of EGFR signaling in the articular cartilage and joints, and to analyze phenotypic consequences of Mig-6 loss on articular cartilage morphology, proliferation, expression of progenitor cell markers, presence of chondrocyte hypertrophy and degradation of articular cartilage matrix. Results The articular cartilage of Mig-6-conditional knockout (Mig-6-cko) mice was dramatically and significantly thicker than normal articular cartilage at 6 and 12 weeks of age. Mig-6-cko articular cartilage contained a population of chondrocytes in which EGFR signaling was activated, and which were three to four times more proliferative than normal Mig-6-flox articular chondrocytes. These cells expressed high levels of the master chondrogenic regulatory factor Sox9, as well as high levels of putative progenitor cell markers including superficial zone protein (SZP), growth and differentiation factor-5 (GDF-5) and Notch1. Expression levels were also high for activated β-catenin and the transforming growth factor beta (TGF-β) mediators phospho-Smad2/3 (pSmad2/3). Anabolic effects of EGFR activation in articular cartilage were followed by catabolic events, including matrix degradation, as determined by accumulation of aggrecan cleavage fragments, and onset of hypertrophy as determined by type × collagen expression. By 16 weeks of age, the articular cartilage of

  5. 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.

  6. Clinical efflux of cryoprotective agents from vitrified human articular cartilage.

    PubMed

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

    2013-04-01

    In previous research, we successfully cryopreserved intact human articular cartilage on its bone base with high chondrocyte viability using a vitrification protocol that entailed sequential exposure to several cryopreserving agents (CPAs) at lowering temperatures resulting in a high final concentration of CPA. The CPA must be removed from the cartilage at warming due to its toxicity to cells in the cryopreserved tissue and the post-transplant adjacent tissues. The current experiment explores the relationship between removal solution volume and time required for complete removal of CPA from bone-cartilage samples. Osteochondral dowels of 10mm diameter from five patients undergoing total knee arthroplasty were vitrified using our protocol resulting in 6.5M CPA within the matrix. In the primary experiment, the warmed dowels were immersed in 10 mL of X-VIVO for 30 min and this was repeated 5 times (the last wash being 5 min only). Removal solution osmolality was recorded at various times and compared to controls of pure X-VIVO. Changes in removal solution osmolality over time were normalized to tissue volume. In a secondary experiment, the procedure was repeated using double the volume of removal solution (20 mL X-VIVO). Results showed a rapid change in the osmolality of the removal solution indicating a rapid efflux of CPA from cartilage. The efflux rate decreased with time and during subsequent immersions until equilibrium was reached during the 4th immersion indicating effectively complete removal of CPA. Doubling the amount of removal solution demonstrated the effective removal of CPAs by the third immersion. The results of this study yield a practical relationship between the amount of removal solution and the time and number of immersions required to remove CPA from the transplantable tissue. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. 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.

  8. Morphological and functional interrelationships of articular cartilage matrices.

    PubMed Central

    Poole, C A; Flint, M H; Beaumont, B W

    1984-01-01

    The pericellular, territorial and interterritorial matrices of canine tibial cartilage have been identified ultrastructurally on the basis of their collagen fibre density and organisation, proteoglycan distribution and their structural response to experimentally applied compressive loads. In addition, a discrete pericellular capsule composed of fine, faintly banded fibrils is described which surrounds and encloses the pericellular matrix and chondrocytes of the middle and deep layers but not of the superficial layer. It is suggested that the fine fibrils which comprise this pericellular capsule represent some of the new minor collagen species recently localised in a similar position in hyaline cartilages. The densely compacted cupola which forms the articular pole of the capsule is frequently penetrated by a clearly defined pericellular channel, consistently orientated in the direction of the articular surface. Membrane-bound vesicles are observed in the pericellular matrix, within the lumen of the pericellular channel and accumulated in the territorial matrix immediately beyond the pericellular channel. The constancy of this distribution pattern strongly suggests a flow of material through the pericellular channel from the pericellular matrix to the territorial matrix and beyond, possibly in response to minute pressure gradients generated during compressive deformation of the non-distensible capsule. Furthermore, it is suggested that the random dispersal and subsequent rupture of matrix vesicles may represent a mechanism whereby chondrocytes, with limited mobility, could exercise homeostatic control over the cartilage matrix at some distance from the cell. Chondrocytes in the deeper layers of canine tibial cartilage are each surrounded by three distinct compartments, a pericellular matrix and capsule, a territorial matrix and an interterritorial matrix. The response of each of these concentric compartments to experimental load suggests that they function

  9. 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.

  10. 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.

  11. 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.

  12. [Prostaglandin E₂: innovative approaches for tissue engineering of articular cartilage].

    PubMed

    Brochhausen-Delius, C

    2014-11-01

    Chronic diseases, traumatic tissue defects and tumor resections lead to irreversible loss of tissue which are usually treated by reconstructive techniques or prostheses. Tissue engineering represents a change of paradigm from the structural replacement of damaged tissue to genuine regeneration of organ-specific tissue with reconstruction of function. Therefore, autologous cells, biomaterials and growth factors are used to achieve this goal. Tissue engineering of articular cartilage is used in this article as an example of the successful identification of prostaglandin E2 (PGE2) as a growth factor during endochondral ossification. In addition PGE2 could be shown to be beneficial for a rapid phenotypical redifferentiation and synthesis of collagen II in human articular chondrocytes. Based on these findings the development of a combined construct of an oriented scaffold and release system is demonstrated. The innovative characterization of these cell-seeded constructs by the use of synchrotron microcomputed tomography (μCT) permits non-destructive analysis even down to the cellular level. Our results indicate new requirements for the pathological anatomical diagnosis with a view to long-term effects of tissue engineering constructs, the biocompatibility of biodegradable biomaterials and even more important the regenerative potential of different lesions, with prediction of the outcome of tissue engineering-based strategies for individual patients.

  13. 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

  14. 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

  15. 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.

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

    PubMed Central

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

    2012-01-01

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

  17. 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

  18. 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.

  19. Identification of latexin by a proteomic analysis in rat normal articular cartilage.

    PubMed

    Pérez, Elizabeth; Gallegos, José L; Cortés, Leticia; Calderón, Karla G; Luna, José C; Cázares, Febe E; Velasquillo, María C; Kouri, Juan B; Hernández, Fidel C

    2010-06-05

    Osteoarthritis (OA) is characterized by degeneration of articular cartilage. Animal models of OA induced are a widely used tool in the study of the pathogenesis of disease. Several proteomic techniques for selective extraction of proteins have provided protein profiles of chondrocytes and secretory patterns in normal and osteoarthritic cartilage, including the discovery of new and promising biomarkers. In this proteomic analysis to study several proteins from rat normal articular cartilage, two-dimensional electrophoresis and mass spectrometry (MS) were used. Interestingly, latexin (LXN) was found. Using an immunohistochemical technique, it was possible to determine its localization within the chondrocytes from normal and osteoarthritic articular cartilage. In this study, 147 proteins were visualized, and 47 proteins were identified by MS. A significant proportion of proteins are involved in metabolic processes and energy (32%), as well as participating in different biological functions including structural organization (19%), signal transduction and molecular signaling (11%), redox homeostasis (9%), transcription and protein synthesis (6%), and transport (6%). The identified proteins were assigned to one or more subcellular compartments.Among the identified proteins, we found some proteins already recognized in other studies such as OA-associated proteins. Interestingly, we identified LXN, an inhibitor of mammalian carboxypeptidases, which had not been described in articular cartilage. Immunolabeling assays for LXN showed a granular distribution pattern in the cytoplasm of most chondrocytes of the middle, deep and calcified zones of normal articular cartilage as well as in subchondral bone. In osteoarthritic cartilage, LXN was observed in superficial and deep zones. This study provides the first proteomic analysis of normal articular cartilage of rat. We identified LXN, whose location was demonstrated by immunolabeling in the chondrocytes from the middle, deep and

  20. Identification of latexin by a proteomic analysis in rat normal articular cartilage

    PubMed Central

    2010-01-01

    Background Osteoarthritis (OA) is characterized by degeneration of articular cartilage. Animal models of OA induced are a widely used tool in the study of the pathogenesis of disease. Several proteomic techniques for selective extraction of proteins have provided protein profiles of chondrocytes and secretory patterns in normal and osteoarthritic cartilage, including the discovery of new and promising biomarkers. In this proteomic analysis to study several proteins from rat normal articular cartilage, two-dimensional electrophoresis and mass spectrometry (MS) were used. Interestingly, latexin (LXN) was found. Using an immunohistochemical technique, it was possible to determine its localization within the chondrocytes from normal and osteoarthritic articular cartilage. Results In this study, 147 proteins were visualized, and 47 proteins were identified by MS. A significant proportion of proteins are involved in metabolic processes and energy (32%), as well as participating in different biological functions including structural organization (19%), signal transduction and molecular signaling (11%), redox homeostasis (9%), transcription and protein synthesis (6%), and transport (6%). The identified proteins were assigned to one or more subcellular compartments. Among the identified proteins, we found some proteins already recognized in other studies such as OA-associated proteins. Interestingly, we identified LXN, an inhibitor of mammalian carboxypeptidases, which had not been described in articular cartilage. Immunolabeling assays for LXN showed a granular distribution pattern in the cytoplasm of most chondrocytes of the middle, deep and calcified zones of normal articular cartilage as well as in subchondral bone. In osteoarthritic cartilage, LXN was observed in superficial and deep zones. Conclusions This study provides the first proteomic analysis of normal articular cartilage of rat. We identified LXN, whose location was demonstrated by immunolabeling in the

  1. 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

  2. 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

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

    PubMed Central

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

    2015-01-01

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

  4. Chondrocyte death in mechanically injured articular cartilage--the influence of extracellular calcium.

    PubMed

    Amin, Anish K; Huntley, James S; Bush, Peter G; Simpson, A Hamish R W; Hall, Andrew C

    2009-06-01

    Calcium is thought to be an important regulator of chondrocyte death associated with articular cartilage injury. Our objective was to determine the influence of extracellular calcium on chondrocyte death following mechanical injury. Using a surgically relevant model of sharp mechanical injury (with a scalpel) and confocal laser scanning microscopy (CLSM), in situ chondrocyte death was quantified within the full thickness of articular cartilage as a function of medium calcium concentration and time (2.5 h and 7 days). Exposure of articular cartilage to calcium-free media (approximately 0 mM) significantly reduced superficial zone chondrocyte death after mechanical injury compared with exposure to calcium-rich media (2-20 mM, ANOVA at 2.5 h, p = 0.002). In calcium-rich media, although the extent of chondrocyte death increased with increasing medium calcium concentration, cell death remained localized to the superficial zone of articular cartilage over 7 days (ANOVA, p < 0.05). However, in calcium-free media, there was an increase in chondrocyte death within deeper zones of articular cartilage over 7 days. The early (within hours) chondroprotective effect in calcium-free media suggests that the use of joint irrigation solutions without added calcium may decrease chondrocyte death from mechanical injury during articular surgery. The delayed (within days) increase in chondrocyte death in calcium-free media supports the use of calcium supplementation in media used during cartilage culture for tissue engineering or transplantation.

  5. Evolutional patterns of articular cartilage following growth plate injury in rats.

    PubMed

    Quintana-Villamandos, M B; Sánchez-Hernández, J J; Delgado-Martos, M J; Delgado-Baeza, E

    2009-09-01

    No study to date has analyzed the damage of the articular cartilage and its relation to growth plate injury. The purpose of this study was to test whether primary injury to the growth plate contributes to secondary damage to the articular cartilage in rats. A total of 109 two-week-old male Wistar rats were allocated to four lesional groups. In group I (controls) no surgery took place. In the remaining animals, an injury was caused in the proximal physis of the left tibia: group II, perichondrial ring injury; group III, direct injury to the growth plate; group IV, traumatic separation of the epiphysis where a Salter-Harris II-type injury was created. The results were assessed at 1 week, 6 weeks, and 6 months. A growth plate score was used. The stereological and histological changes in the articular cartilage were analyzed, and the results were subjected to statistical analysis. Histological studies showed discrete degenerative changes in the articular cartilage in the injured growth plate. Changes in the cell density, mean cell volume, and articular cartilage occurred in the injured growth plate. The changes appeared to be transient in groups II and III. Primary injury to the growth plate contributes to secondary damage to the articular cartilage in young rats. Our data -- extrapolated to the clinical view -- suggests that a Salter-Harris type II injury does not seem to have impunity to subsequent joint degeneration.

  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. An ultrasound study of altered hydration behaviour of proteoglycan-degraded articular cartilage

    PubMed Central

    2013-01-01

    Background Articular cartilage is a solid-fluid biphasic material covering the bony ends of articulating joints. Hydration of articular cartilage is important to joint lubrication and weight-wearing. The aims of this study are to measure the altered hydration behaviour of the proteoglycan-degraded articular cartilage using high-frequency ultrasound and then to investigate the effect of proteoglycan (PG) degradation on cartilage hydration. Methods Twelve porcine patellae with smooth cartilage surface were prepared and evenly divided into two groups: normal group without any enzyme treatment and trypsin group treated with 0.25% trypsin solution for 4 h to digest PG in the tissue. After 40-minute exposure to air at room temperature, the specimens were immerged into the physiological saline solution. The dehydration induced hydration behaviour of the specimen was monitored by the high-frequency (25 MHz) ultrasound pulser/receiver (P/R) system. Dynamic strain and equilibrium strain were extracted to quantitatively evaluate the hydration behaviour of the dehydrated cartilage tissues. Results The hydration progress of the dehydrated cartilage tissue was observed in M-mode ultrasound image indicating that the hydration behaviour of the PG-degraded specimens decreased. The percentage value of the equilibrium strain (1.84 ± 0.21%) of the PG-degraded cartilage significantly (p < 0.01) decreased in comparison with healthy cartilage (3.46 ± 0.49%). The histological sections demonstrated that almost PG content in the entire cartilage layer was digested by trypsin. Conclusion Using high-frequency ultrasound, this study found a reduction in the hydration behaviour of the PG-degraded cartilage. The results indicated that the degradation of PG decreased the hydration capability of the dehydrated tissue. This study may provide useful information for further study on changes in the biomechanical property of articular cartilage in osteoarthritis. PMID:24119051

  13. [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

  14. 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

  15. Comparison of friction and wear of articular cartilage on different length scales.

    PubMed

    Kienle, Sandra; Boettcher, Kathrin; Wiegleb, Lorenz; Urban, Joanna; Burgkart, Rainer; Lieleg, Oliver; Hugel, Thorsten

    2015-09-18

    The exceptional tribological properties of articular cartilage are still far from being fully understood. Articular cartilage is able to withstand high loads and provide exceptionally low friction. Although the regeneration abilities of the tissue are very limited, it can last for many decades. These biomechanical properties are realized by an interplay of different lubrication and wear protection mechanisms. The deterioration of cartilage due to aging or injury leads to the development of osteoarthritis. A current treatment strategy focuses on supplementing the intra-articular fluid with a saline solution containing hyaluronic acid. In the work presented here, we investigated how changing the lubricating fluid affects friction and wear of articular cartilage, focusing on the boundary and mixed lubrication as well as interstitial fluid pressurization mechanisms. Different length and time scales were probed by atomic force microscopy, tribology and profilometry. We compared aqueous solutions with different NaCl concentrations to a viscosupplement containing hyaluronic acid (HA). In particular, we found that the presence of ions changes the frictional behavior and the wear resistance. In contrast, hyaluronic acid showed no significant impact on the friction coefficient, but considerably reduced wear. This study confirms the previous notion that friction and wear are not necessarily correlated in articular cartilage tribology and that the main role of HA might be to provide wear protection for the articular surface. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. In Situ measurement of transport between subchondral bone and articular cartilage

    PubMed Central

    Pan, Jun; Zhou, Xiaozhou; Li, Wen; Novotny, John E.; Doty, Stephen B.; Wang, Liyun

    2009-01-01

    Subchondral bone and articular cartilage play complementary roles in load bearing of the joints. Although the biomechanical coupling between subchondral bone and articular cartilage is well established, it remains unclear whether direct biochemical communication exists between them. The calcified cartilage between these two compartments was generally believed to be impermeable to transport of solutes and gases, previously. However, recent studies found that small molecules could penetrate into the calcified cartilage from the subchondral bone. To quantify the real-time solute transport across the calcified cartilage, we developed a novel imaging method based on fluorescence loss induced by photobleaching (FLIP). Diffusivity of sodium fluorescein (376 Da) was quantified to be 0.07±0.03 and 0.26±0.22 μm2/sec between subchondral bone and calcified cartilage and within the calcified cartilage in the murine distal femur, respectively. Electron microscopy revealed that calcified cartilage matrix contained non-mineralized regions (∼22% volume fraction) that are either large patches (53±18 nm) among the mineral deposits or numerous small regions (4.5±0.8 nm) within the mineral deposits, which may serve as transport pathways. These results suggest that there exists a possible direct signaling between subchondral bone and articular cartilage, and they form a functional unit with both mechanical and biochemical interactions, which may play a role in the maintenance and degeneration of the joint. PMID:19360842

  17. 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

  18. 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

  19. Association between quantitative MRI and ICRS arthroscopic grading of articular cartilage.

    PubMed

    Casula, Victor; Hirvasniemi, Jukka; Lehenkari, Petri; Ojala, Risto; Haapea, Marianne; Saarakkala, Simo; Lammentausta, Eveliina; Nieminen, Miika T

    2016-06-01

    To investigate the association of quantitative magnetic resonance imaging (qMRI) parameters with arthroscopic grading of cartilage degeneration. Arthroscopy of the knee is considered to be the gold standard of osteoarthritis diagnostics; however, it is operator-dependent and limited to the evaluation of the articular surface. qMRI provides information on the quality of articular cartilage and its changes even at early stages of a disease. qMRI techniques included T 1 relaxation time, T 2 relaxation time, and delayed gadolinium-enhanced MRI of cartilage mapping at 3 T in ten patients. Due to a lack of generally accepted semiquantitative scoring systems for evaluating severity of cartilage degeneration during arthroscopy, the International Cartilage Repair Society (ICRS) classification system was used to grade the severity of cartilage lesions. qMRI parameters were statistically compared to arthroscopic grading conducted with the ICRS classification system. qMRI parameters were not linearly related to arthroscopic grading. Spearman's correlation coefficients between qMRI and arthroscopic grading were not significant. The relative differences in qMRI parameters of superficial and deep cartilage varied with degeneration, suggesting different macromolecular alterations in different cartilage zones. Results suggest that loss of cartilage and the quality of remaining tissue in the lesion site may not be directly associated with each other. The severity of cartilage degeneration may not be revealed solely by diagnostic arthroscopy, and thus, qMRI can have a role in the investigation of cartilage degeneration.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2002-09-01

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

  9. Contrast agent-enhanced computed tomography of articular cartilage: association with tissue composition and properties.

    PubMed

    Silvast, T S; Jurvelin, J S; Aula, A S; Lammi, M J; Töyräs, J

    2009-01-01

    Contrast agent-enhanced computed tomography may enable the noninvasive quantification of glycosaminoglycan (GAG) content of articular cartilage. It has been reported that penetration of the negatively charged contrast agent ioxaglate (Hexabrix) increases significantly after enzymatic degradation of GAGs. However, it is not known whether spontaneous degradation of articular cartilage can be quantitatively detected with this technique. To investigate the diagnostic potential of contrast agent-enhanced cartilage tomography (CECT) in quantification of GAG concentration in normal and spontaneously degenerated articular cartilage by means of clinical peripheral quantitative computed tomography (pQCT). In this in vitro study, normal and spontaneously degenerated adult bovine cartilage (n=32) was used. Bovine patellar cartilage samples were immersed in 21 mM contrast agent (Hexabrix) solution for 24 hours at room temperature. After immersion, the samples were scanned with a clinical pQCT instrument. From pQCT images, the contrast agent concentration in superficial as well as in full-thickness cartilage was calculated. Histological and functional integrity of the samples was quantified with histochemical and mechanical reference measurements extracted from our earlier study. Full diffusion of contrast agent into the deep cartilage was found to take over 8 hours. As compared to normal cartilage, a significant increase (11%, P<0.05) in contrast agent concentration was seen in the superficial layer of spontaneously degenerated samples. Significant negative correlations were revealed between the contrast agent concentration and the superficial or full-thickness GAG content of tissue (|R| > 0.5, P<0.01). Further, pQCT could be used to measure the thickness of patellar cartilage. The present results suggest that CECT can be used to diagnose proteoglycan depletion in spontaneously degenerated articular cartilage with a clinical pQCT scanner. Possibly, the in vivo use of clinical p

  10. 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.

  11. 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.

  12. [Tribological assessment of articular cartilage. A system for the analysis of the friction coefficient of cartilage, regenerates and tissue engineering constructs; initial results].

    PubMed

    Schwarz, M L R; Schneider-Wald, B; Krase, A; Richter, W; Reisig, G; Kreinest, M; Heute, S; Pott, P P; Brade, J; Schütte, A

    2012-10-01

    Values for the friction coefficient of articular cartilage are given in ranges of percentage and lower and are calculated as a quotient of the friction force and the perpendicular loading force acting on it. Thus, a sophisticated system has to be provided for analysing the friction coefficient under different conditions in particular when cartilage should be coupled as friction partner. It is possible to deep-freeze articular cartilage before measuring the friction coefficient as the procedure has no influence on the results. The presented tribological system was able to distinguish between altered and native cartilage. Furthermore, tissue engineered constructs for cartilage repair were differentiated from native cartilage probes by their friction coefficient. In conclusion a tribological equipment is presented to analyze the friction coefficient of articular cartilage, in vivo generated cartilage regenerates and in vitro tissue engineered constructs regarding their biomechanical properties for quality assessment.

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

    PubMed Central

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

    2010-01-01

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

  14. 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

  15. Recapitulation of physiological spatiotemporal signals promotes in vitro formation of phenotypically stable human articular cartilage

    PubMed Central

    Wei, Yiyong; Zhou, Bin; Bernhard, Jonathan; Robinson, Samuel; Burapachaisri, Aonnicha; Guo, X. Edward

    2017-01-01

    Standard isotropic culture fails to recapitulate the spatiotemporal gradients present during native development. Cartilage grown from human mesenchymal stem cells (hMSCs) is poorly organized and unstable in vivo. We report that human cartilage with physiologic organization and in vivo stability can be grown in vitro from self-assembling hMSCs by implementing spatiotemporal regulation during induction. Self-assembling hMSCs formed cartilage discs in Transwell inserts following isotropic chondrogenic induction with transforming growth factor β to set up a dual-compartment culture. Following a switch in the basal compartment to a hypertrophic regimen with thyroxine, the cartilage discs underwent progressive deep-zone hypertrophy and mineralization. Concurrent chondrogenic induction in the apical compartment enabled the maintenance of functional and hyaline cartilage. Cartilage homeostasis, chondrocyte maturation, and terminal differentiation markers were all up-regulated versus isotropic control groups. We assessed the in vivo stability of the cartilage formed under different induction regimens. Cartilage formed under spatiotemporal regulation in vitro resisted endochondral ossification, retained the expression of cartilage markers, and remained organized following s.c. implantation in immunocompromised mice. In contrast, the isotropic control groups underwent endochondral ossification. Cartilage formed from hMSCs remained stable and organized in vivo. Spatiotemporal regulation during induction in vitro recapitulated some aspects of native cartilage development, and potentiated the maturation of self-assembling hMSCs into stable and organized cartilage resembling the native articular cartilage. PMID:28228529

  16. Dependence of nanoscale friction and adhesion properties of articular cartilage on contact load.

    PubMed

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

    2011-04-29

    Boundary lubrication of articular cartilage by conformal, molecularly thin films reduces friction and adhesion between asperities at the cartilage-cartilage contact interface when the contact conditions are not conducive to fluid film lubrication. In this study, the nanoscale friction and adhesion properties of articular cartilage from typical load-bearing and non-load-bearing joint regions were studied in the boundary lubrication regime under a range of physiological contact pressures using an atomic force microscope (AFM). Adhesion of load-bearing cartilage was found to be much lower than that of non-load-bearing cartilage. In addition, load-bearing cartilage demonstrated steady and low friction coefficient through the entire load range examined, whereas non-load-bearing cartilage showed higher friction coefficient that decreased nonlinearly with increasing normal load. AFM imaging and roughness calculations indicated that the above trends in the nanotribological properties of cartilage are not due to topographical (roughness) differences. However, immunohistochemistry revealed consistently higher surface concentration of boundary lubricant at load-bearing joint regions. The results of this study suggest that under contact conditions leading to joint starvation from fluid lubrication, the higher content of boundary lubricant at load-bearing cartilage sites preserves synovial joint function by minimizing adhesion and wear at asperity microcontacts, which are precursors for tissue degeneration. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. 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).

  18. 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.

  19. Viscoelastic properties of human and bovine articular cartilage: a comparison of frequency-dependent trends.

    PubMed

    Temple, Duncan K; Cederlund, Anna A; Lawless, Bernard M; Aspden, Richard M; Espino, Daniel M

    2016-10-06

    The purpose of this study was to compare the frequency-dependent viscoelastic properties of human and bovine cartilage. Full-depth cartilage specimens were extracted from bovine and human femoral heads. Using dynamic mechanical analysis, the viscoelastic properties of eight bovine and six human specimens were measured over the frequency range 1 Hz to 88 Hz. Significant differences between bovine and human cartilage viscoelastic properties were assessed using a Mann-Whitney test (p < 0.05). Throughout the range of frequencies tested and for both species, the storage modulus was greater than the loss modulus and both were frequency-dependent. The storage and loss moduli of all human and bovine cartilage specimens presented a logarithmic relationship with respect to frequency. The mean human storage modulus ranged from 31.9 MPa to 43.3 MPa, while the mean bovine storage modulus ranged from 54.0 MPa to 80.5 MPa; bovine storage moduli were 1.7 to 1.9 times greater than the human modulus. Similarly, the loss modulus of bovine cartilage was 2.0 to 2.1 times greater than human. The mean human loss modulus ranged from 5.3 MPa to 8.5 MPa while bovine moduli ranged from 10.6 MPa to 18.1 MPa. Frequency-dependent viscoelastic trends of bovine articular cartilage were consistent with those of human articular cartilage; this includes a similar frequency dependency and high-frequency plateau. Bovine cartilage was, however, 'stiffer' than human by a factor of approximately 2. With these provisos, bovine articular cartilage may be a suitable dynamic model for human articular cartilage.

  20. 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.

  1. 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.

  2. Relationship between synovial fluid biomarkers of articular cartilage metabolism and the patient's perspective of outcome depends on the severity of articular cartilage damage following ACL trauma.

    PubMed

    Wasilko, Scott M; Tourville, Timothy W; DeSarno, Michael J; Slauterbeck, James R; Johnson, Robert J; Struglics, André; Beynnon, Bruce D

    2016-05-01

    Anterior cruciate ligament (ACL) trauma often occurs in combination with injury to the articular cartilage of the knee, this can result in earlier radiographic evidence of post traumatic osteoarthritis (OA) of the knee compared to the contralateral, ACL intact knee; however, the biomechanical and biological mechanisms associated with the onset and progression of this disease are not understood. We sought to gain insight into the mechanisms by determining the relationship between articular cartilage injury associated with ACL trauma and the expression of synovial fluid biomarkers of articular cartilage metabolism, and to evaluate the relationship between these biomarkers and the patient's perspective of the outcomes. Synovial fluid samples were acquired from 39 ACL injured subjects at an average of 10 weeks after injury, and 32 control subjects with normal knees (documented with clinical exam and MRI assessment). Subjects in the ACL-injured group were classified as low-risk for future OA if they displayed an International Cartilage Repair Society (ICRS) Grade 2 articular cartilage lesion or less and high-risk for future OA if they had an ICRS Grade 3A articular cartilage lesion. The patient's perspective of the injury was evaluated with the Knee Injury and Osteoarthritis Outcomes Score (KOOS). There were no significant differences in mean concentrations of the markers of type II collagen metabolism (CPII, C2C, and C1,2C) or the aggrecan breakdown Alanine-Arginine-Glycine-Serine (ARGS) -fragment between control subjects and the subjects in the low- and high-risk groups (p-value range: 0.80-0.43). Associations between ARGS-aggrecan concentration and KOOS subscales of symptoms and pain were significantly different between the low- and high-risk groups (p = 0.03 and p = 0.01, respectively). Likewise, there was strong evidence in support of an association between the markers of type II collagen metabolism (C1,2C and CPII concentrations) and the KOOS subscale of

  3. Hypointense signal lesions of the articular cartilage: a review of current concepts.

    PubMed

    Markhardt, B Keegan; Chang, Eric Y

    2014-01-01

    Discussion of articular cartilage disease detection by MRI usually focuses on the presence of bright signal on T2-weighted sequences, such as in Grade 1 chondromalacia and cartilage fissures containing fluid. Less emphasis has been placed on how cartilage disease may be manifested by dark signal on T2-weighted sequences. The appearance of the recently described "cartilage black line sign" of the femoral trochlea highlights these lesions and further raises the question of their etiology. We illustrate various hypointense signal lesions that are not restricted to the femoral trochlea of the knee joint and discuss the possible etiologies for these lesions. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Arthroscopic laser in intra-articular knee cartilage disorders

    NASA Astrophysics Data System (ADS)

    Nosir, Hany R.; Siebert, Werner E.

    1996-12-01

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

  5. Direct Quantification of Solute Diffusivity in Agarose and Articular Cartilage Using Correlation Spectroscopy.

    PubMed

    Shoga, Janty S; Graham, Brian T; Wang, Liyun; Price, Christopher

    2017-06-13

    Articular cartilage is an avascular tissue; diffusive transport is critical for its homeostasis. While numerous techniques have been used to quantify diffusivity within porous, hydrated tissues and tissue engineered constructs, these techniques have suffered from issues regarding invasiveness and spatial resolution. In the present study, we implemented and compared two separate correlation spectroscopy techniques, fluorescence correlation spectroscopy (FCS) and raster image correlation spectroscopy (RICS), for the direct, and minimally-invasive quantification of fluorescent solute diffusion in agarose and articular cartilage. Specifically, we quantified the diffusional properties of fluorescein and Alexa Fluor 488-conjugated dextrans (3k and 10k) in aqueous solutions, agarose gels of varying concentration (i.e. 1, 3, 5%), and in different zones of juvenile bovine articular cartilage explants (i.e. superficial, middle, and deep). In agarose, properties of solute diffusion obtained via FCS and RICS were inversely related to molecule size, gel concentration, and applied strain. In cartilage, the diffusional properties of solutes were similarly dependent upon solute size, cartilage zone, and compressive strain; findings that agree with work utilizing other quantification techniques. In conclusion, this study established the utility of FCS and RICS as simple and minimally invasive techniques for quantifying microscale solute diffusivity within agarose constructs and articular cartilage explants.

  6. 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.

  7. 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.

  8. Intravascular Ultrasound (IVUS): A Potential Arthroscopic Tool for Quantitative Assessment of Articular Cartilage.

    PubMed

    Huang, Yan-Ping; Zheng, Yong-Ping

    2009-06-26

    Conventional ultrasound examination of the articular cartilage performed externally on the body surface around the joint has limited accuracy due to the inadequacy in frequency used. In contrast to this, minimally invasive arthroscopy-based ultrasound with adequately high frequency may be a better alternative to assess the cartilage. Up to date, no special ultrasound transducer for imaging the cartilage in arthroscopic use has been designed. In this study, we introduced the intravascular ultrasound (IVUS) for this purpose. An IVUS system with a catheter-based probe (Ø approximately 1mm) was used to measure the thickness and surface acoustical reflection of the bovine patellar articular cartilage in vitro before and after degeneration induced by enzyme treatments. Similar measurement was performed using another high frequency ultrasound system (Vevo) with a probe of much larger size and the results were compared between the two systems. The thickness measured using IVUS was highly correlated (r = 0.985, p < 0.001) with that obtained by Vevo. Thickness and surface reflection amplitude measured using IVUS on the enzymatically digested articular cartilage showed changes similar to those obtained by Vevo, which were expectedly consistent with previous investigations. IVUS can be potentially used for the quantitative assessment of articular cartilage, with its ready-to-use arthroscopic feature.

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

    PubMed

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

    2015-02-01

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

  10. 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.

  11. 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

  12. Automatic segmentation of the articular cartilage in knee MRI using a hierarchical multi-class classification scheme.

    PubMed

    Folkesson, Jenny; Dam, Erik; Olsen, Ole Fogh; Pettersen, Paola; Christiansen, Claus

    2005-01-01

    Osteoarthritis is characterized by the degeneration of the articular cartilage in joints. We have developed a fully automatic method for segmenting the articular cartilage in knee MR scans based on supervised learning. A binary approximate kNN classifier first roughly separates cartilage from background voxels, then a three-class classifier assigns one of three classes to each voxel that is classified as cartilage by the binary classifier. The resulting sensitivity and specificity are 90.0% and 99.8% respectively for the medial cartilage compartments. We show that an accurate automatic cartilage segmentation is achievable using a low-field MR scanner.

  13. Correlation between apparent diffusion coefficient and viscoelasticity of articular cartilage in a porcine model.

    PubMed

    Aoki, T; Watanabe, A; Nitta, N; Numano, T; Fukushi, M; Niitsu, M

    2012-09-01

    Quantitative MR imaging techniques of degenerative cartilage have been reported as useful indicators of degenerative changes in cartilage extracellular matrix, which consists of proteoglycans, collagen, non-collagenous proteins, and water. Apparent diffusion coefficient (ADC) mapping of cartilage has been shown to correlate mainly with the water content of the cartilage. As the water content of the cartilage in turn correlates with its viscoelasticity, which directly affects the mechanical strength of articular cartilage, ADC can serve as a potentially useful indicator of the mechanical strength of cartilage. The aim of this study was to investigate the correlation between ADC and viscoelasticity as measured by indentation testing. Fresh porcine knee joints (n = 20, age 6 months) were obtained from a local abattoir. ADC of porcine knee cartilage was measured using a 3-Tesla MRI. Indentation testing was performed on an electromechanical precision-controlled system, and viscosity coefficient and relaxation time were measured as additional indicators of the viscoelasticity of cartilage. The relationship between ADC and viscosity coefficient as well as that between ADC and relaxation time were assessed. ADC was correlated with relaxation time and viscosity coefficient (R(2) = 0.75 and 0.69, respectively, p < 0.01). The mean relaxation time values in the weight-bearing and non-weight-bearing regions were 0.61 ± 0.17 ms and 0.14 ± 0.08 ms, respectively. This study found a moderate correlation between ADC and viscoelasticity in the superficial articular cartilage. Both molecular diffusion and viscoelasticity were higher in weight bearing than non-weight-bearing articular cartilage areas.

  14. 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.

  15. Noninvasive assessment of articular cartilage surface damage using reflected polarized light microscopy.

    PubMed

    Huynh, Ruby N; Nehmetallah, George; Raub, Christopher B

    2017-06-01

    Articular surface damage occurs to cartilage during normal aging, osteoarthritis, and in trauma. A noninvasive assessment of cartilage microstructural alterations is useful for studies involving cartilage explants. This study evaluates polarized reflectance microscopy as a tool to assess surface damage to cartilage explants caused by mechanical scraping and enzymatic degradation. Adult bovine articular cartilage explants were scraped, incubated in collagenase, or underwent scrape and collagenase treatments. In an additional experiment, cartilage explants were subject to scrapes at graduated levels of severity. Polarized reflectance parameters were compared with India ink surface staining, features of histological sections, changes in explant wet weight and thickness, and chondrocyte viability. The polarized reflectance signal was sensitive to surface scrape damage and revealed individual scrape features consistent with India ink marks. Following surface treatments, the reflectance contrast parameter was elevated and correlated with image area fraction of India ink. After extensive scraping, polarized reflectance contrast and chondrocyte viability were lower than that from untreated explants. As part of this work, a mathematical model was developed and confirmed the trend in the reflectance signal due to changes in surface scattering and subsurface birefringence. These results demonstrate the effectiveness of polarized reflectance microscopy to sensitively assess surface microstructural alterations in articular cartilage explants.

  16. Noninvasive assessment of articular cartilage surface damage using reflected polarized light microscopy

    NASA Astrophysics Data System (ADS)

    Huynh, Ruby N.; Nehmetallah, George; Raub, Christopher B.

    2017-06-01

    Articular surface damage occurs to cartilage during normal aging, osteoarthritis, and in trauma. A noninvasive assessment of cartilage microstructural alterations is useful for studies involving cartilage explants. This study evaluates polarized reflectance microscopy as a tool to assess surface damage to cartilage explants caused by mechanical scraping and enzymatic degradation. Adult bovine articular cartilage explants were scraped, incubated in collagenase, or underwent scrape and collagenase treatments. In an additional experiment, cartilage explants were subject to scrapes at graduated levels of severity. Polarized reflectance parameters were compared with India ink surface staining, features of histological sections, changes in explant wet weight and thickness, and chondrocyte viability. The polarized reflectance signal was sensitive to surface scrape damage and revealed individual scrape features consistent with India ink marks. Following surface treatments, the reflectance contrast parameter was elevated and correlated with image area fraction of India ink. After extensive scraping, polarized reflectance contrast and chondrocyte viability were lower than that from untreated explants. As part of this work, a mathematical model was developed and confirmed the trend in the reflectance signal due to changes in surface scattering and subsurface birefringence. These results demonstrate the effectiveness of polarized reflectance microscopy to sensitively assess surface microstructural alterations in articular cartilage explants.

  17. 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.

  18. 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.

  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. 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.

  2. 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.

  3. Gremlin 1, frizzled-related protein, and Dkk-1 are key regulators of human articular cartilage homeostasis.

    PubMed

    Leijten, J C H; Emons, J; Sticht, C; van Gool, S; Decker, E; Uitterlinden, A; Rappold, G; Hofman, A; Rivadeneira, F; Scherjon, S; Wit, J M; van Meurs, J; van Blitterswijk, C A; Karperien, M

    2012-10-01

    The development of osteoarthritis (OA) may be caused by activation of hypertrophic differentiation of articular chondrocytes. Healthy articular cartilage is highly resistant to hypertrophic differentiation, in contrast to other hyaline cartilage subtypes, such as growth plate cartilage. The purpose of this study was to elucidate the molecular mechanism responsible for the difference in the propensity of human articular cartilage and growth plate cartilage to undergo hypertrophic differentiation. Whole-genome gene-expression microarray analysis of healthy human growth plate and articular cartilage derived from the same adolescent donors was performed. Candidate genes, which were enriched in the articular cartilage, were validated at the messenger RNA (mRNA) and protein levels and examined for their potential to inhibit hypertrophic differentiation in two models. In addition, we studied a possible genetic association with OA. Pathway analysis demonstrated decreased Wnt signaling in articular cartilage as compared to growth plate cartilage. This was at least partly due to increased expression of the bone morphogenetic protein and Wnt antagonists Gremlin 1, Frizzled-related protein (FRP), and Dkk-1 at the mRNA and protein levels in articular cartilage. Supplementation of these proteins diminished terminal hypertrophic differentiation without affecting chondrogenesis in long-bone explant cultures and chondrogenically differentiating human mesenchymal stem cells. Additionally, we found that single-nucleotide polymorphism rs12593365, which is located in a genomic control region of GREM1, was significantly associated with a 20% reduced risk of radiographic hip OA in 2 population-based cohorts. Taken together, our study identified Gremlin 1, FRP, and Dkk-1 as natural brakes on hypertrophic differentiation in articular cartilage. As hypertrophic differentiation of articular cartilage may contribute to the development of OA, our findings may open new avenues for therapeutic

  4. 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.

  5. Arthroscopic Ultrasound Assessment of Articular Cartilage in the Human Knee Joint

    PubMed Central

    Kaleva, Erna; Virén, Tuomas; Saarakkala, Simo; Sahlman, Janne; Sirola, Joonas; Puhakka, Jani; Paatela, Teemu; Kröger, Heikki; Kiviranta, Ilkka; Jurvelin, Jukka S.; Töyräs, Juha

    2011-01-01

    Objective: We tested whether an intra-articular ultrasound (IAUS) method could be used to evaluate cartilage status arthroscopically in human knee joints in vivo. Design: Seven patients undergoing arthroscopic surgery of the knee were enrolled in this study. An ultrasonic examination was conducted using the same portals as in the arthroscopic surgery. A high-frequency (40-MHz) ultrasound transducer (diameter = 1 mm) was directed to the desired location on the articular surface under arthroscopic control. In addition to ultrasound data, an IAUS video and optical video through the arthroscope were recorded. Classification of cartilage injuries according to International Cartilage Repair Society, as conducted by the orthopedic surgeon, provided reference data for comparison with the IAUS. Results: The IAUS method was successful in imaging different characteristics of the articular surfaces (e.g., intact surface, surface fibrillation, and lesions of varying depth). In some cases, also the subchondral bone and abnormal internal cartilage structure were visible in the IAUS images. Specifically, using the IAUS, a local cartilage lesion of 1 patient was found to be deeper than estimated arthroscopically. Conclusions: The IAUS method provided a novel arthroscopic method for quantitative imaging of articular cartilage lesions. The IAUS provided quantitative information about the cartilage integrity and thickness, which are not available in conventional arthroscopy. The present equipment is already approved by the Food and Drug Administration for intravascular use and might be transferred to intra-articular use. The invasiveness of the IAUS method might restrict its wider clinical use but combined with arthroscopy, ultrasonic assessment may enlarge the diagnostic potential of arthroscopic surgery. PMID:26069583

  6. [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.

  7. Pregnane X Receptor Knockout Mice Display Aging-Dependent Wearing of Articular Cartilage

    PubMed Central

    Azuma, Kotaro; Casey, Stephanie C.; Urano, Tomohiko; Horie-Inoue, Kuniko; Ouchi, Yasuyoshi; Blumberg, Bruce; Inoue, Satoshi

    2015-01-01

    Steroid and xenobiotic receptor (SXR) and its murine ortholog, pregnane X receptor (PXR), are nuclear receptors that are expressed at high levels in the liver and the intestine where they function as xenobiotic sensors that induce expression of genes involved in detoxification and drug excretion. Recent evidence showed that SXR and PXR are also expressed in bone tissue where they mediate bone metabolism. Here we report that systemic deletion of PXR results in aging-dependent wearing of articular cartilage of knee joints. Histomorphometrical analysis showed remarkable reduction of width and an enlarged gap between femoral and tibial articular cartilage in PXR knockout mice. We hypothesized that genes induced by SXR in chondrocytes have a protective effect on articular cartilage and identified Fam20a (family with sequence similarity 20a) as an SXR-dependent gene induced by the known SXR ligands, rifampicin and vitamin K2. Lastly, we demonstrated the biological significance of Fam20a expression in chondrocytes by evaluating osteoarthritis-related gene expression of primary articular chondrocytes. Consistent with epidemiological findings, our results indicate that SXR/PXR protects against aging-dependent wearing of articular cartilage and that ligands for SXR/PXR have potential role in preventing osteoarthritis caused by aging. PMID:25749104

  8. Atomic force microscope investigation of the boundary-lubricant layer in articular cartilage.

    PubMed

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

    2010-07-01

    To determine the roles of superficial zone protein (SZP), hyaluronan (HA), and surface-active phospholipids (SAPL) in boundary lubrication of articular cartilage through systematic enzyme digestion using trypsin, hyaluronidase, and phospolipase-C (PLC) surface treatments. The friction coefficient of articular cartilage surfaces was measured with an atomic force microscope (AFM) before and after enzyme digestion. Surface roughness, adhesion, and stiffness of the articular surface were also measured to determine the mechanism of friction in the boundary lubrication regime. Histology and transmission electron microscopy were used to visualize the surface changes of treatment groups that showed significant friction changes after enzyme digestion. A significant increase in the friction coefficient of both load-bearing and non load-bearing regions of the joint was observed after proteolysis by trypsin. Treatment with trypsin, hyaluronidase, or PLC did not affect the surface roughness. However, trypsin treatment decreased the adhesion significantly. Results indicate that the protein component at the articular cartilage surface is the main boundary lubricant, with SZP being a primary candidate. The prevailing nanoscale deformation processes are likely plastic and/or viscoelastic in nature, suggesting that plowing is the dominant friction mechanism. The findings of this study indicate that SZP plays an intrinsic and critical role in boundary lubrication at the articular surface of cartilage, whereas the effects of HA and SAPL on the tribological behavior are marginal. Copyright 2010 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. Cartilage lesions in feline stifle joints - Associations with articular mineralizations and implications for osteoarthritis.

    PubMed

    Leijon, Alexandra; Ley, Charles J; Corin, Antonia; Ley, Cecilia

    2017-04-19

    Feline stifle osteoarthritis (OA) is common, however little is known about the early stages of the disease. Furthermore, the importance of small articular mineralizations (AMs) in feline stifle OA is controversial. This study aimed to describe microscopic articular cartilage lesions and to investigate associations between cartilage lesions and AMs, synovitis, osteochondral junction findings and subchondral bone sclerosis. Stifles of 29 cats, aged 1-23years and euthanized for reasons other than stifle disease, were examined. Osteochondral tissue and synovial membrane changes were histologically evaluated. Computed tomography and radiography were used for evaluation of AMs. Global cartilage scores (GCS, n=28) were summarized and joints assigned a histologic OA grade. Minimal to mild histologic OA was seen in 24/28 joints. In 27/29 joints tibial cartilage lesions were seen, whereas femoral lesions were only seen in two joints. Articular mineralizations were detected in 13/29 joints, 11 were small and 12 were located entirely within the medial meniscus. There was no association between GCS and presence or volumes of AMs. However, higher GCS was associated with synovitis (P=0.001) and age (P<0.0005). Presence of subchondral bone sclerosis (P<0.0005) and disruption of the calcified cartilage or tidemark (P<0.0005) were associated with cartilage lesions. We conclude that the tibial articular cartilage is a common location for histologic OA lesions in cats. Synovitis and changes in the subchondral bone and calcified cartilage may be important in the pathogenesis of feline stifle OA, whereas small AMs likely represent incidental findings. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    PubMed Central

    2014-01-01

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

  16. 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.

  17. 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

  18. PGA-associated heterotopic chondrocyte cocultures: implications of nasoseptal and auricular chondrocytes in articular cartilage repair.

    PubMed

    El Sayed, K; Marzahn, U; John, T; Hoyer, M; Zreiqat, H; Witthuhn, A; Kohl, B; Haisch, A; Schulze-Tanzil, G

    2013-01-01

    The availability of autologous articular chondrocytes remains a limiting issue in matrix assisted autologous chondrocyte transplantation. Non-articular heterotopic chondrocytes could be an alternative autologous cell source. The aims of this study were to establish heterotopic chondrocyte cocultures to analyze cell-cell compatibilities and to characterize the chondrogenic potential of nasoseptal chondrocytes compared to articular chondrocytes. Primary porcine and human nasoseptal and articular chondrocytes were investigated for extracellular cartilage matrix (ECM) expression in a monolayer culture. 3D polyglycolic acid- (PGA) associated porcine heterotopic mono- and cocultures were assessed for cell vitality, types II, I, and total collagen-, and proteoglycan content. The type II collagen, lubricin, and Sox9 gene expressions were significantly higher in articular compared with nasoseptal monolayer chondrocytes, while type IX collagen expression was lower in articular chondrocytes. Only β1-integrin gene expression was significantly inferior in humans but not in porcine nasoseptal compared with articular chondrocytes, indicating species-dependent differences. Heterotopic chondrocytes in PGA cultures revealed high vitality with proteoglycan-rich hyaline-like ECM production. Similar amounts of type II collagen deposition and type II/I collagen ratios were found in heterotopic chondrocytes cultured on PGA compared to articular chondrocytes. Quantitative analyses revealed a time-dependent increase in total collagen and proteoglycan content, whereby the differences between heterotopic and articular chondrocyte cultures were not significant. Nasoseptal and auricular chondrocytes monocultured in PGA or cocultured with articular chondrocytes revealed a comparable high chondrogenic potential in a tissue engineering setting, which created the opportunity to test them in vivo for articular cartilage repair. Copyright © 2011 John Wiley & Sons, Ltd.

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

    PubMed Central

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

    2016-01-01

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

  20. Molecular Characterization of Articular Cartilage from Young Adults with Femoroacetabular Impingement

    PubMed Central

    Hashimoto, Shingo; Rai, Muhammad Farooq; Gill, Corey S.; Zhang, Zhiqi; Sandell, Linda J.; Clohisy, John C.

    2013-01-01

    Background: Femoroacetabular impingement is a frequent cause of hip pain and may lead to secondary osteoarthritis, yet little is known about the molecular events linking mechanical hip impingement and articular cartilage degeneration. The first goal of this study was to quantify the expression of inflammatory cytokine and chemokine, matrix-degrading, and extracellular matrix genes in articular cartilage harvested from control hips and hips with femoroacetabular impingement and end-stage osteoarthritis. The second goal was to analyze the relative expression of these genes in articular cartilage harvested at various stages of osteoarthritis. Methods: Cartilage samples were obtained from thirty-two hips undergoing hip preservation surgery for femoroacetabular impingement or hip arthroplasty. Three control cartilage samples were also analyzed. Specimens were graded intraoperatively with regard to the severity of cartilage damage, the radiographic osteoarthritis grade was recorded, and quantitative RT-PCR (real-time polymerase chain reaction) was performed to determine relative gene expression. Results: Except for interleukin-1β (IL-1β) and CXCL2, the mRNA (messenger RNA) expression of all other chemokine (IL-8, CXCL1, CXCL3, CXCL6, CCL3, and CCL3L1), matrix-degrading (matrix metalloproteinase [MMP]-13 and ADAMTS-4), and structural matrix (COL2A1 [collagen, type II, alpha] and ACAN [aggregan]) genes was higher overall in cartilage from hips with femoroacetabular impingement compared with hips with osteoarthritis and normal controls. The differences reached significance (p ≤ 0.05) for seven of these ten quantified genes, with CXCL3, CXCL6, and COL2A1 being elevated in the femoroacetabular impingement group compared with only the control group and IL-8, CCL3L1, ADAMTS-4, and ACAN being elevated compared with both the osteoarthritis and control groups. When samples were grouped according to the stage of the degenerative cascade, mRNA expression was relatively higher in

  1. 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

  2. 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.

  3. Establishment of a reliable method for direct proteome characterization of human articular cartilage.

    PubMed

    Vincourt, Jean-Baptiste; Lionneton, Frédéric; Kratassiouk, Gueorgui; Guillemin, François; Netter, Patrick; Mainard, Didier; Magdalou, Jacques

    2006-10-01

    Articular cartilage consists mainly of extracellular matrix, mostly made of collagens and proteoglycans. These macromolecules have so far impaired the detailed two-dimensional electrophoresis-based proteomic analysis of articular cartilage. Here we describe a method for selective protein extraction from cartilage, which excludes proteoglycans and collagen species, thus allowing direct profiling of the protein content of cartilage by two-dimensional electrophoresis. Consistent electrophoretic patterns of more than 600 protein states were reproducibly obtained after silver staining from 500 mg of human articular cartilage from joints with diverse pathologies. The extraction yield increased when the method was applied to a chondrosarcoma sample, consistent with selective extraction of cellular components. Nearly 200 of the most intensely stained protein spots were analyzed by MALDI-TOF mass spectrometry after trypsin digestion. They represented 127 different proteins with diverse functions. Our method provides a rapid, efficient, and pertinent alternative to previously proposed approaches for proteomic characterization of cartilage phenotypes. It will be useful for detecting protein expression patterns that relate pathophysiological processes of cartilaginous tissues such as osteoarthritis and chondrosarcoma.

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

    PubMed

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

    2009-11-21

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

  5. Functional Properties of Chondrocytes and Articular Cartilage using Optical Imaging to Scanning Probe Microscopy.

    PubMed

    Xia, Yang; Darling, Eric M; Herzog, Walter

    2017-10-03

    Mature chondrocytes in adult articular cartilage vary in number, size, and shape, depending on their depth in the tissue, location in the joint, and source species. Chondrocytes are the primary structural, functional, and metabolic unit in articular cartilage, the loss of which will induce fatigue to the extracellular matrix (ECM), eventually leading to failure of the cartilage and impairment of the joint as a whole. This brief review focuses on the functional and biomechanical studies of chondrocytes and articular cartilage, using microscopic imaging from optical microscopies to scanning probe microscopy. Three topics are covered in this review, including the functional studies of chondrons by optical imaging (unpolarized and polarized light and infrared light, two-photon excitation microscopy), the probing of chondrocytes and cartilage directly using microscale measurement techniques, and different imaging approaches that can measure chondrocyte mechanics and chondrocyte biological signaling under in situ and in vivo environments. Technical advancement in chondrocyte research during recent years has enabled new ways to study the biomechanical and functional properties of these cells and cartilage. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  6. 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.

  7. 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

  8. Hyaline Articular Matrix Formed by Dynamic Self-Regenerating Cartilage and Hydrogels.

    PubMed

    Meppelink, Amanda M; Zhao, Xing; Griffin, Darvin J; Erali, Richard; Gill, Thomas J; Bonassar, Lawrence J; Redmond, Robert W; Randolph, Mark A

    2016-07-01

    Injuries to the articular cartilage surface are challenging to repair because cartilage possesses a limited capacity for self-repair. The outcomes of current clinical procedures aimed to address these injuries are inconsistent and unsatisfactory. We have developed a novel method for generating hyaline articular cartilage to improve the outcome of joint surface repair. A suspension of 10(7) swine chondrocytes was cultured under reciprocating motion for 14 days. The resulting dynamic self-regenerating cartilage (dSRC) was placed in a cartilage ring and capped with fibrin and collagen gel. A control group consisted of chondrocytes encapsulated in fibrin gel. Constructs were implanted subcutaneously in nude mice and harvested after 6 weeks. Gross, histological, immunohistochemical, biochemical, and biomechanical analyses were performed. In swine patellar groove, dSRC was implanted into osteochondral defects capped with collagen gel and compared to defects filled with osteochondral plugs, collagen gel, or left empty after 6 weeks. In mice, the fibrin- and collagen-capped dSRC constructs showed enhanced contiguous cartilage matrix formation over the control of cells encapsulated in fibrin gel. Biochemically, the fibrin and collagen gel dSRC groups were statistically improved in glycosaminoglycan and hydroxyproline content compared to the control. There was no statistical difference in the biomechanical data between the dSRC groups and the control. The swine model also showed contiguous cartilage matrix in the dSRC group but not in the collagen gel and empty defects. These data demonstrate the survivability and successful matrix formation of dSRC under the mechanical forces experienced by normal hyaline cartilage in the knee joint. The results from this study demonstrate that dSRC capped with hydrogels successfully engineers contiguous articular cartilage matrix in both nonload-bearing and load-bearing environments.

  9. 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

  10. 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.

  11. Tissue engineering of functional articular cartilage: the current status.

    PubMed

    Kock, Linda; van Donkelaar, Corrinus C; Ito, Keita

    2012-03-01

    Osteoarthritis is a degenerative joint disease characterized by pain and disability. It involves all ages and 70% of people aged >65 have some degree of osteoarthritis. Natural cartilage repair is limited because chondrocyte density and metabolism are low and cartilage has no blood supply. The results of joint-preserving treatment protocols such as debridement, mosaicplasty, perichondrium transplantation and autologous chondrocyte implantation vary largely and the average long-term result is unsatisfactory. One reason for limited clinical success is that most treatments require new cartilage to be formed at the site of a defect. However, the mechanical conditions at such sites are unfavorable for repair of the original damaged cartilage. Therefore, it is unlikely that healthy cartilage would form at these locations. The most promising method to circumvent this problem is to engineer mechanically stable cartilage ex vivo and to implant that into the damaged tissue area. This review outlines the issues related to the composition and functionality of tissue-engineered cartilage. In particular, the focus will be on the parameters cell source, signaling molecules, scaffolds and mechanical stimulation. In addition, the current status of tissue engineering of cartilage will be discussed, with the focus on extracellular matrix content, structure and its functionality.

  12. Biologic Options for Articular Cartilage Wear (Platelet-Rich Plasma, Stem Cells, Bone Marrow Aspirate Concentrate).

    PubMed

    Kraeutler, Matthew J; Chahla, Jorge; LaPrade, Robert F; Pascual-Garrido, Cecilia

    2017-07-01

    Biological treatments for articular cartilage repair have gained in popularity in the past decade. Advantages of these therapies include minimal invasiveness, improved healing time, and faster recovery. Biological therapies for cartilage repair include platelet-rich plasma, bone marrow aspirate concentrate, and cell-based therapies. These methods have the added benefit of containing growth factors and/or stem cells that aid in recovery and regeneration. The purpose of this article is to review the current cartilage treatment options and the existing literature on outcomes, complications, and safety profile of these products for use in the knee and hip joints. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Protection of the Proximal Articular Cartilage During Percutaneous Thermal Ablation of Acetabular Metastasis Using Temperature Monitoring.

    PubMed

    Bauones, Salem; Garnon, Julien; Chari, Basavaraj; Cazzato, Roberto L; Tsoumakidou, Georgia; Caudrelier, Jean; Koch, Guillaume; Gangi, Afshin

    2017-07-24

    To review our initial experience in acetabular cartilage protection from thermal injury with temperature monitoring during percutaneous image-guided tumor thermal ablation. Between June 2015 and December 2016, three consecutive oncologic patients (mean age 58 years; range 48-67 years) with acetabular bone metastasis underwent percutaneous image-guided thermal ablation procedures along with hip joint cartilage thermal monitoring. Due to the close proximity of the metastatic lesion to the acetabular articular cartilage, a thermosensor device was placed under CT and fluoroscopic guidance near the acetabular roof and next to the ablation zone in order to monitor the local temperature around the articular cartilage. Stand-alone thermal ablation (n = 1) and combined thermal ablation with cementoplasty (n = 2) were performed to optimize local palliation or disease control. Clinical and radiological outcomes at follow-up were assessed. Three acetabular metastatic lesions were treated with thermal ablation, and temperature monitoring of the acetabular articular cartilage was conducted during the ablation procedure. Mean size of lesions was 1.6 cm (range 1.5-2 cm). Technical success was achieved in all cases (100%) without any immediate complications. No hip cartilage damage occurred clinically and radiologically. Good palliation and local disease control were achieved in two cases, and in the other case, there was local recurrence and distant progression of hip metastatic disease after 7 months of follow-up. Temperature monitoring of the articular cartilage during percutaneous image-guided thermal ablation appears technically feasible with good short-term efficacy in a complex patient subset. Further studies are warranted to confirm these promising initial results.

  14. Effects of moving training on histology and biomarkers levels of articular cartilage.

    PubMed

    Qi, Chang; Changlin, Huang

    2006-10-01

    To study the adaptation process and extent of articular cartilage in the canine knee joint to different modes of movements and to investigate if levels of cartilage oligomeric matrix protein (COMP), matrix metalloproteinases-1 (MMP-1), matrix metalloproteinases-3 (MMP-3), and tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) in serum and synovial fluid can be used to predict effectively early sports injury and remolding degree of articular cartilage in the canine knee. Twenty adult dogs divided randomly into three groups (eight in the common training group, Training Group; eight in the intensified training group, Intensified Group; and four in the Control Group) were trained daily at different intensities. Magnetic resonance imaging (MRI) examinations were performed regularly (0, 2, 4, 6, 8, 10 weeks) to investigate changes of articular cartilage in the canine knee, while concentrations of COMP, MMP-1, MMP-3, and TIMP-1 in serum and synovial fluid were measured by ELISA assays. All of the dogs were euthanized after training for 10 weeks, and all of the knee joints were taken out to be examined histologically. We could find imaging changes of early sport injury of articular cartilage in the Training Group and Intensified Group by MRI examination after 2 weeks of training; the damage images were most severe in 4-6 weeks, and then lightened gradually. We could not find the difference of cartilage injury and repair degree in MRI images between these two groups at different time points. Elevations of levels of COMP, MMP-1, MMP-3, TIMP-1, and MMP-3/TIMP-1 in serum and synovial fluid were seen during the training period, and their levels changed remarkably at different times. Levels of MMP-1, MMP-3, and MMP-3/TIMP-1 in the Intensified Group were lower than that in the Training Group in general, and levels of COMP were higher, which hinted that the injury trend of articular cartilage in the Intensified Group was lower than that in the Training group, and the repair

  15. 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.

  16. Effects of osmotic challenges on membrane potential in human articular chondrocytes from healthy and osteoarthritic cartilage.

    PubMed

    Sánchez, Julio C; López-Zapata, Diego F

    2010-01-01

    Changes in external osmolarity arise from variations in mechanical loads on joints and may affect the homeostasis of chondrocytes, which are the only cell type responsible for matrix turnover. Accordingly, variations in membrane potential may affect cartilage production. The present study assessed the effects of variations in external osmolarity on membrane potential and the possible mechanisms responsible for this response. Membrane potential was measured by the patch clamp whole-cell technique using human articular chondrocytes freshly isolated from healthy and osteoarthritic cartilage. The membrane potential was -39±4 mV in articular human chondrocytes from healthy cartilage and -26±4 mV in those from osteoarthritic cartilage. Increasing the osmolarity produced a reversible hyperpolarization mediated by K+ efflux through BKCa channels in both groups of chondrocytes, but the response in osteoarthritic cells was significantly reduced; no other K+ pathways were involved in this effect. Alternatively, decreasing the osmolarity elicited depolarization in healthy chondrocytes but did not produce any response in chondrocytes from osteoarthritic cartilage. The depolarization was dependent on Na+ influx through Gd3+-sensitive stretch-activated cation channels and was independent of external Ca2+. The differential responses observed in chondrocytes from osteoarthritic cartilage suggest that disregulation on the responses to external osmolarity may be involved in the process that leads to the alterations in the cartilage structure observed in osteoarthritis.

  17. 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)

  18. The role of type X collagen in facilitating and regulating endochondral ossification of articular cartilage.

    PubMed

    Shen, G

    2005-02-01

    AUTHOR: Shen G Objective -This review was compiled to explore the role of type X collagen in growth, development and remodeling of articular cartilage by elucidating the linkage between the synthesis of this protein and the phenotypic changes in chondrogenesis and the onset of endochondral ossification. The current studies closely dedicated to elucidating the role of type X collagen incorporating into chondrogenesis and endochondral ossification of articular cartilage were assessed and analyzed to allow for obtaining the mainstream consensus on the bio-molecular mechanism with which type X collagen functions in articular cartilage. There are spatial and temporal correlations between synthesis of type X collagen and occurrence of endochondral ossification. The expression of type X collagen is confined within hypertrophic condrocytes and precedes the embark of endochondral bone formation. Type X collagen facilitates endochondral ossification by regulating matrix mineralization and compartmentalizing matrix components. Type X collagen is a reliable marker for new bone formation in articular cartilage. The future clinical application of this collagen in inducing or mediating endochondral ossification is perceived, e.g. the fracture healing of synovial joints and adaptive remodeling of madibular condyle.

  19. Poly(vinyl alcohol) hydrogel as a biocompatible viscoelastic mimetic for articular cartilage.

    PubMed

    Grant, Colin; Twigg, Pete; Egan, Alex; Moody, Alexandra; Smith, Annie; Eagland, Donald; Crowther, Nicholas; Britland, Steve

    2006-01-01

    The prevalence of suboptimal outcome for surgical interventions in the treatment of full-thickness articular cartilage damage suggests that there is scope for a materials-based strategy to deliver a more durable repair. Given that the superficial layer of articular cartilage creates and sustains the tribological function of synovial joints, it is logical that candidate materials should have surface viscoelastic properties that mimic native articular cartilage. The present paper describes force spectroscopy analysis by nano-indentation to measure the elastic modulus of the surface of a novel poly(vinyl alcohol) hydrogel with therapeutic potential as a joint implant. More than 1 order of magnitude decrease in the elastic modulus was detected after adsorption of a hyaluronic acid layer onto the hydrogel, bringing it very close to previously reported values for articular cartilage. Covalent derivatization of the hydrogel surface with fibronectin facilitated the adhesion and growth of cultured rat tibial condyle chondrocytes as evidenced morphologically and by the observance of metachromatic staining with toluidine blue dye. The present results indicate that hydrogel materials with potential therapeutic benefit for injured and diseased joints can be engineered with surfaces with biomechanical properties similar to those of native tissue and are accepted as such by their constituent cell type.

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

    USDA-ARS?s Scientific Manuscript database

    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...

  1. Infrared microspectroscopic determination of collagen cross-links in articular cartilage

    NASA Astrophysics Data System (ADS)

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

    2017-03-01

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

  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. Evidence to suggest that cathepsin K degrades articular cartilage in naturally occurring equine osteoarthritis.

    PubMed

    Vinardell, T; Dejica, V; Poole, A R; Mort, J S; Richard, H; Laverty, S

    2009-03-01

    The mechanisms leading to degeneration of articular cartilage in osteoarthritis (OA) are complex and not yet fully understood. Cathepsin K (CK) is a cysteine protease which can also cleave the triple helix of type II collagen. This exposes a neoepitope that can now be identified by specific antibodies. The aim of this study was to obtain evidence suggesting a role for CK in naturally occurring equine OA in both lesional and peri-lesional regions. Articular cartilages (n=12 horses; 5 healthy, 7 OA) were harvested from animals postmortem. A gross macroscopic examination, histologic (Safranin O-Fast Green and Picrosirius red staining) and immunohistochemical evaluation were performed. Samples were divided into normal appearing cartilage, peri-lesional and lesional cartilage. Cartilage degradation in the samples was graded histologically and immunohistochemically. CK and possible CK cleavage were detected immunohistochemically with specific anti-protein and anti-neoepitope antibodies, respectively. A comparison of CK neoepitope (C2K) production with the collagenase-generated neoepitope produced by matrix metalloproteinases (MMP)-1, 8 and 13 (C2C) was also assessed immunohistochemically. CK and CK cleavage were significantly more abundant in OA cartilage (both peri-lesional and lesional) when compared to remote cartilage within the sample joint or cartilage from healthy joints. The immunohistochemical pattern observed for CK degradation (C2K) was similar to that of collagenase degradation (C2C). Macroscopic cartilage changes and histologic findings were significantly correlated with immunohistochemistry results. The data generated suggests that CK may be involved in cartilage collagen degradation in naturally occurring osteoarthritis.

  7. 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

  8. 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.

  9. Enhancing Chondrogenic Phenotype for Cartilage Tissue Engineering: Monoculture and Coculture of Articular Chondrocytes and Mesenchymal Stem Cells

    PubMed Central

    Hubka, Kelsea M.; Dahlin, Rebecca L.; Meretoja, Ville V.; Kasper, F. Kurtis

    2014-01-01

    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. PMID:24834484

  10. 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.

  11. 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.

  12. 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.

  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. 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

  15. Danshen prevents articular cartilage degeneration via antioxidation in rabbits with osteoarthritis.

    PubMed

    Bai, B; Li, Y

    2016-03-01

    To evaluate the efficacy of Danshen on histological parameters and antioxidative activity in the articular cartilage of rabbits with osteoarthritis (OA). Twenty-four rabbits were randomly divided into three groups (control, OA, and Danshen OA; eight rabbits per group). Anterior cruciate ligament transection (ACLT) of the left hind knees was performed in all rabbits in the OA and Danshen OA group for induction of OA. The rabbits in the control group underwent a sham operation. After surgery, 3 g/kg body weight of Danshen granules dissolved in 5 mL distilled water was administered by gastric intubation once per day and over a 6-week period to the Danshen OA group. The same volume of distilled water was administered to the OA and control groups. After 6 weeks, the medial femoral condyles and synoviums of the left hind knees in all three groups were harvested and used for histological and biochemical analyses. Severe articular cartilage degeneration as well as lower proteoglycan (PG) content were noted in the OA group compared to the Danshen OA group (P < 0.05). The glutathione (GSH) levels in the synovium and articular cartilage of the rabbits in the Danshen OA group were significantly higher compared to the OA group (P < 0.001). The malondialdehyde (MDA) levels of the synovium and articular cartilage in the Danshen OA group was markedly depleted compared to the OA group (P < 0.001). Danshen can prevent articular cartilage degeneration in OA through the defense against oxidative stress. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  16. 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

  17. 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.

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

    PubMed Central

    Ateshian, Gerard A.

    2009-01-01

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

  19. Characterization of auricular chondrocytes and auricular/articular chondrocyte co-cultures in terms of an application in articular cartilage repair.

    PubMed

    Kuhne, Maren; John, Thilo; El-Sayed, Karym; Marzahn, Ulrike; Aue, Annekatrin; Kohl, Benjamin; Stoelzel, Katharina; Ertel, Wolfgang; Blottner, Dieter; Haisch, Andreas; Schulze-Tanzil, Gundula

    2010-05-01

    Cartilage injury remains a challenge in orthopedic surgery as articular cartilage only has a limited capacity for intrinsic healing. Autologous chondrocyte transplantation (ACT) is a suitable technique for cartilage repair, but requires articular cartilage biopsies for autologous chondrocyte expansion. The use of heterotopic chondrocytes derived from non-articular cartilage sources such as auricular chondrocytes may be a novel approach for ACT. The aim of the study is to evaluate whether co-cultured articular/auricular chondrocytes exhibit characteristics comparable to articular chondrocytes. Analysis of the proliferation rate, extracellular cartilage matrix (ECM) gene and protein expression (type II and I collagen, elastin, lubricin), beta1-integrins and the chondrogenic transcription factor sox9 in articular/auricular chondrocytes was performed using RTD-PCR, flow cytometry, immunofluorescence microscopy and Western blot analysis. Additionally, three-dimensional (3D) chondrocyte mono- and co-cultures were established. The proliferative activity and elastin gene expression were lower and that of type II collagen and lubricin was higher in articular compared with auricular chondrocytes. The species generally did not influence the chondrocyte characteristics, with the exception of type I collagen and sox9 expression, which was higher in porcine but not in human articular chondrocytes compared with both types of auricular chondrocytes. beta1-integrin gene expression did not differ significantly between the chondrocyte types. The type II collagen gene and protein expression was higher in articular chondrocyte monocultures and was slightly higher in co-cultures compared with monocultured auricular chondrocytes. Both chondrocyte types survived in co-culture. Despite their differing expression profiles, co-cultures revealed some adjustment in the ECM expression of both chondrocyte types.

  20. 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

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

    PubMed Central

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

    2014-01-01

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

  2. 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.

  3. Load distribution of articular cartilage from MR-images by neural nets.

    PubMed

    Seidel, Peter; Hanke, Göran; Gründer, Wilfried

    2005-01-01

    Artificial neural nets were used to determine the Young's modulus and spatial load distribution in articular cartilage by means of T2-weighted MR imaging. MR images were obtained in vitro (ex vivo?) from the joints of sheep of different ages (3 months, 9 months, 15 months, 1.5 years, 5 years, 5.5 years) and pigs (4 and 6 months) with a Bruker AMX 300 (7 T) spectrometer equipped with a micro-imaging unit. The knee of a 29-year-old male volunteer was studied in vivo under mechanical load using a clinical Siemens Vision MRT (1.5 T). The load of the cartilage is understood as a non-linear image transformation of loaded versus unloaded images. The artificial neural net was used to recognize given reference pixels of the unloaded cartilage within the image of the loaded cartilage. The Young's modulus was calculated from the local strain and the external pressure using the Hooke's law. With this method, the average Young's modulus was obtained in relationship to the biological age of the cartilage. The investigated age interval showed a progressive increase of 0.5 +/- 0.3 MPa per year. These results are consistent with published results. As shown in this pilot study, the method of neural nets allows the visualization of the spatial load distribution within the articular cartilage.

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

    PubMed

    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; Guilak, Farshid; Liedtke, Wolfgang B

    2014-11-25

    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 Ca(2+) signals and electrical currents compared with single-Piezo expression. In primary articular chondrocytes, mechanically evoked Ca(2+) 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.

  5. 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

  6. 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

  7. 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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. 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

  9. 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.

  10. Histomorphometric analysis of adult articular calcified cartilage zone.

    PubMed

    Wang, Fuyou; Ying, Zhang; Duan, Xiaojun; Tan, Hongbo; Yang, Bin; Guo, Lin; Chen, Guangxing; Dai, Gang; Ma, Zhe; Yang, Liu

    2009-12-01

    The aim of this study was to carry out a histomorphometric analysis of calcified cartilage zone (CCZ) and its interfaces between hyaline cartilage and subchondral bone. The study used 40 donated normal human femoral condyles, from which paraffin-embedded sections were prepared after fixation and decalcification. The histomorphology of the CCZ were qualitatively and quantitatively observed by staining, scanning electron microscopy (SEM) and three-dimensional (3D) reconstruction. The hyaline cartilage and CCZ were stained red with Safranin-O, and the subchondral bone was stained blue with Fast green. CCZ was stained black after von Kossa staining. The hyaline cartilage was interlocked tightly in the manner of "ravine-engomphosis" by the CCZ. The surface roughnesses of tidemark and cement line were 1.14+/-0.04 and 1.99+/-0.38. The maximum, minimum and mean thicknesses of CCZ were 277.12+/-8.6, 9.83+/-6.72 and 104.162+/-0.87 microm, respectively. The cell density of CCZ (51.25+/-21.26 cells/mm(2)) was significantly lower than that of the hyaline cartilage (152.54+/-35.77 cells/mm(2)) (P<0.05). The subchondral bone was anchored tightly in the manner of a "comb-anchor" by the CCZ in our 3D reconstruction model. Thus, we discovered two junctional interfaces of CCZ using different histomorphometric methods. The upper interface of CCZ is a "ravine-engomphosis" shape, while its lower interface is a "comb-anchor" shape.

  11. 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.

  12. 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.

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

    PubMed

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

    2016-04-01

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

  14. 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.

  15. 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.

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

    NASA Astrophysics Data System (ADS)

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

    1992-06-01

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

  17. 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

  18. 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.

  19. Registration of Magnetic Resonance Image Series for Knee Articular Cartilage Analysis

    PubMed Central

    Urish, Kenneth L.; Williams, Ashley A.; Durkin, John R.

    2013-01-01

    Objective: Although conventional radiography is used to assess osteoarthritis in a clinical setting, it has limitations, including an inability to stage early cartilage degeneration. There is a growing interest in using quantitative magnetic resonance imaging to identify degenerative changes in articular cartilage, including the large multicentered study, the Osteoarthritis Initiative (OAI). There is a demand for suitable image registration and segmentation software to complete this analysis. The objective of this study was to develop and validate the open source software, ImageK, that registers 3 T MRI T2 mapping and double echo steady state (DESS) knee MRI sequences acquired in the OAI protocol. Methods: A C++ library, the insight toolkit, was used to develop open source software to register DESS and T2 mapping image MRI sequences using Mattes’s Multimodality Mutual information metric. Results: Registration was assessed using three separate methods. A checkerboard layout demonstrated acceptable visual alignment. Fiducial markers placed in cadaveric knees measured a registration error of 0.85 voxels. Measuring the local variation in Mattes’s Mutual Information metric in the local area of the registered solution showed precision within 1 pixel. In this group, the registered solution required a transform of 56 voxels in translation and 1 degree of rotation. Conclusion: The software we have developed, ImageK, provides free, open source image analysis software that registers DESS and T2 mapping sequences of knee articular cartilage within 1 voxel accuracy. This image registration software facilitates quantitative MRI analyses of knee articular cartilage. PMID:23997865

  20. 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.

  1. 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.

  2. The role of viscoelasticity of collagen fibers in articular cartilage: theory and numerical formulation.

    PubMed

    Li, L P; Herzog, W

    2004-01-01

    The relative importance of fluid-dependent and fluid-independent transient mechanical behavior in articular cartilage was examined for tensile and unconfined compression testing using a fibril reinforced model. The collagen matrix of articular cartilage was modeled as viscoelastic using a quasi-linear viscoelastic formulation with strain-dependent elastic modulus, while the proteoglycan matrix was considered as linearly elastic. The collagen viscoelastic properties were obtained by fitting experimental data from a tensile test. These properties were used to investigate unconfined compression testing, and the sensitivity of the properties was also explored. It was predicted that the stress relaxation observed in tensile tests was not caused by fluid pressurization at the macroscopic level. A multi-step tensile stress relaxation test could be approximated using a hereditary integral in which the elastic fibrillar modulus was taken to be a linear function of the fibrillar strain. Applying the same formulation to the radial fibers in unconfined compression, stress relaxation could not be simulated if fluid pressurization were absent. Collagen viscoelasticity was found to slightly weaken fluid pressurization in unconfined compression, and this effect was relatively more significant at moderate strain rates. Therefore, collagen viscoelasticity appears to play an import role in articular cartilage in tensile testing, while fluid pressurization dominates the transient mechanical behavior in compression. Collagen viscoelasticity plays a minor role in the mechanical response of cartilage in unconfined compression if significant fluid flow is present.

  3. Magnetic resonance imaging (MRI) of articular cartilage in knee osteoarthritis (OA): morphological assessment.

    PubMed

    Eckstein, F; Cicuttini, F; Raynauld, J-P; Waterton, J C; Peterfy, C

    2006-01-01

    Magnetic resonance imaging (MRI) is a three-dimensional imaging technique with unparalleled ability to evaluate articular cartilage. This report reviews the current status of morphological assessment of cartilage with quantitative MRI (qMRI), and its relevance for identifying disease status, and monitoring progression and treatment response in knee osteoarthritis (OA). An international panel of experts in MRI of knee OA, with direct experience in the analysis of cartilage morphology with qMRI, reviewed the existing published and unpublished data on the subject, and debated the findings at the OMERACT-OARSI Workshop on Imaging technologies (December 2002, Bethesda, MA) with scientists and clinicians from academia, the pharmaceutical industry and the regulatory agencies. This report reviews (1) MRI pulse sequence considerations for morphological analysis of articular cartilage; (2) techniques for segmenting cartilage; (3) semi-quantitative scoring of cartilage status; and (4) technical validity (accuracy), precision (reproducibility) and sensitivity to change of quantitative measures of cartilage morphology. Semi-quantitative scores of cartilage status have been shown to display adequate reliability, specificity and sensitivity, and to detect lesion progression at reasonable observation periods (1-2 years). Quantitative assessment of cartilage morphology (qMRI), with fat-suppressed gradient echo sequences, and appropriate image analysis techniques, displays high accuracy and adequate precision (e.g., root-mean-square standard deviation medial tibia=61 microl) for cross-sectional and longitudinal studies in OA patients. Longitudinal studies suggest that changes of cartilage volume of the order of -4% to -6% occur per annum in OA in most knee compartments (e.g., -90 microl in medial tibia). Annual changes in cartilage volume exceed the precision errors and appear to be associated with clinical symptoms as well as with time to knee arthroplasty. MRI provides reliable

  4. Site-specific ultrasound reflection properties and superficial collagen content of bovine knee articular cartilage

    NASA Astrophysics Data System (ADS)

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

    2005-07-01

    Previous quantitative 2D-ultrasound imaging studies have demonstrated that the ultrasound reflection measurement of articular cartilage surface sensitively detects degradation of the collagen network, whereas digestion of cartilage proteoglycans has no significant effect on the ultrasound reflection. In this study, the first aim was to characterize the ability of quantitative 2D-ultrasound imaging to detect site-specific differences in ultrasound reflection and backscattering properties of cartilage surface and cartilage-bone interface at visually healthy bovine knee (n = 30). As a second aim, we studied factors controlling ultrasound reflection properties of an intact cartilage surface. The ultrasound reflection coefficient was determined in time (R) and frequency domains (IRC) at medial femoral condyle, lateral patello-femoral groove, medial tibial plateau and patella using a 20 MHz ultrasound imaging instrument. Furthermore, cartilage surface roughness was quantified by calculating the ultrasound roughness index (URI). The superficial collagen content of the cartilage was determined using a FT-IRIS-technique. A significant site-dependent variation was shown in cartilage thickness, ultrasound reflection parameters, URI and superficial collagen content. As compared to R and IRC, URI was a more sensitive parameter in detecting differences between the measurement sites. Ultrasound reflection parameters were not significantly related to superficial collagen content, whereas the correlation between R and URI was high. Ultrasound reflection at the cartilage-bone interface showed insignificant site-dependent variation. The current results suggest that ultrasound reflection from the intact cartilage surface is mainly dependent on the cartilage surface roughness and the collagen content has a less significant role.

  5. 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.

  6. 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

  7. 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.

  8. 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

  9. Loss of Extracellular Matrix from Articular Cartilage is Mediated by the Synovium and Ligament after Anterior Cruciate Ligament Injury

    PubMed Central

    Haslauer, Carla M.; Elsaid, Khaled A.; Fleming, Braden C.; Proffen, Benedikt L.; Johnson, Victor M.; Murray, Martha M.

    2014-01-01

    Objective Post-traumatic osteoarthritis (PTOA) occurs after anterior cruciate ligament (ACL) injury. PTOA may be initiated by early expression of proteolytic enzymes capable of causing degradation of the articular cartilage at time of injury. This study investigated the production of three of these key proteases in multiple joint tissues after ACL injury and subsequent markers of cartilage turnover. Design ACL transection was performed in adolescent minipigs. Collagenase (MMP-1 and MMP-13) and aggrecanase (ADAMTS-4) gene expression changes were quantified in the articular cartilage, synovium, injured ligament, and the provisional scaffold at days 1, 5, 9, and 14 post-injury. Markers of collagen degradation (C2C), synthesis (CPII) and aggrecan synthesis (CS846) were quantified in the serum and synovial fluid. Histologic assessment of the cartilage integrity (OARSI scoring) was also performed. Results MMP-1 gene expression was upregulated in the articular cartilage, synovium and ligament after ACL injury. MMP-13 expression was suppressed in the articular cartilage, but upregulated 100fold in the synovium and ligament. ADAMTS-4 was upregulated in the synovium and ligament but not in the articular cartilage. The concentration of collagen degradation fragments (C2C) in the synovial joint fluid nearly doubled in the first five days after injury. Conclusion We conclude that upregulation of genes coding for proteins capable of degrading cartilage ECM is seen within the first few days after ACL injury, and this response is seen not only in chondrocytes, but also in cells in the synovium, ligament and provisional scaffold. PMID:24036379

  10. Strain-rate-dependent non-linear tensile properties of the superficial zone of articular cartilage.

    PubMed

    Ahsanizadeh, Sahand; Li, LePing

    2015-11-01

    The tensile properties of articular cartilage play an important role in the compressive behavior and integrity of the tissue. The stress-strain relationship of cartilage in compression was observed previously to depend on the strain-rate. This strain-rate dependence has been thought to originate mainly from fluid pressurization. However, it was not clear to what extent the tensile properties of cartilage contribute to the strain-rate dependence in compressive behavior of cartilage. The aim of the present study was to quantify the strain-rate dependent stress-strain relationship and hysteresis of articular cartilage in tension. Uniaxial tensile tests were performed to examine the strain-rate dependent non-linear tensile properties of the superficial zone of bovine knee cartilage. Tensile specimens were oriented in the fiber direction indicated by the India ink method. Seven strain-rates were used in the measurement ranging from 0.1 to 80%/s, which corresponded to nearly static to impact joint loadings. The experimental data showed substantial strain-rate and strain-magnitude dependent load response: for a given strain-magnitude, the tensile stress could vary by a factor of 1.95 while the modulus by a factor of 1.58 with strain-rate; for a given strain-rate, the modulus at 15% strain could be over four times the initial modulus at no strain. The energy loss in cartilage tension upon unloading exhibited a complex variation with the strain-rate. The strain-rate dependence of cartilage in tension observed from the present study is relatively weaker than that in compression observed previously, but is considerable to contribute to the strain-rate dependent load response in compression.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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. © 2012 The Authors Journal of Microscopy © 2012 Royal Microscopical Society.

  16. 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.

  17. 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.

  18. 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.

  19. Machine learning classification of OARSI-scored human articular cartilage using magnetic resonance imaging

    PubMed Central

    Ashinsky, Beth G.; Coletta, Christopher E.; Bouhrara, Mustapha; Lukas, Vanessa A.; Boyle, Julianne M.; Reiter, David A.; Neu, Corey P.; Goldberg, Ilya G.; Spencer, Richard G.

    2015-01-01

    Objective The purpose of this study is to evaluate the ability of machine learning to discriminate between magnetic resonance images (MRI) of normal and pathological human articular cartilage obtained under standard clinical conditions. Method An approach to MRI classification of cartilage degradation is proposed using pattern recognition and multivariable regression in which image features from MRIs of histologically scored human articular cartilage plugs were computed using weighted neighbor distance using compound hierarchy of algorithms representing morphology (WND-CHRM). The WND-CHRM method was first applied to several clinically available MRI scan types to perform binary classification of normal and osteoarthritic osteochondral plugs based on the OARSI histological system. In addition, the image features computed from WND-CHRM were used to develop a multiple linear least-squares regression model for classification and prediction of an OARSI score for each cartilage plug. Results The binary classification of normal and osteoarthritic plugs yielded results of limited quality with accuracies between 36% and 70%. However, multiple linear least-squares regression successfully predicted OARSI scores and classified plugs with accuracies as high as 86%. The present results improve upon the previously-reported accuracy of classification using average MRI signal intensities and parameter values. Conclusion MRI features detected by WND-CHRM reflect cartilage degradation status as assessed by OARSI histologic grading. WND-CHRM is therefore of potential use in the clinical detection and grading of osteoarthritis. PMID:26067517

  20. Effects of enrofloxacin and magnesium deficiency on matrix metabolism in equine articular cartilage.

    PubMed

    Davenport, C L; Boston, R C; Richardson, D W

    2001-02-01

    To investigate the effects of enrofloxacin and magnesium deficiency on explants of equine articular cartilage. Articular cartilage explants and cultured chondrocytes obtained from adult and neonatal horses. Full-thickness explants and cultured chondrocytes were incubated in complete or magnesium-deficient media containing enrofloxacin at concentrations of 0, 1, 5, 25, 100, and 500 microg/ml. Incorporation and release of sulfate 35S over 24 hours were used to assess glycosaminoglycan (GAG) synthesis and degradation. An assay that measured binding of dimethylmethylene blue dye was used to compare total GAG content between groups. Northern blots of RNA from cultured chondrocytes were probed with equine cDNA of aggrecan, type-II collagen, biglycan, decorin, link protein, matrix metalloproteinases 1, 3, and 13, and tissue inhibitor of metalloproteinase 1. A dose-dependent suppression of 35S incorporation was observed. In cartilage of neonates, 35S incorporation was substantially decreased at enrofloxacin concentrations of 25 mg/ml. In cartilage of adult horses, 35S incorporation was decreased only at enrofloxacin concentrations of > or =100 microg/ml. Magnesium deficiency caused suppression of 35S incorporation. Enrofloxacin or magnesium deficiency did not affect GAG degradation or endogenous GAG content. Specific effects of enrofloxacin on steady-state mRNA for the various genes were not observed. Enrofloxacin may have a detrimental effect on cartilage metabolism in horses, especially in neonates.

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

    PubMed Central

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

    2007-01-01

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

  2. 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. Analysis of in-vivo articular cartilage contact surface of the knee during a step-up motion.

    PubMed

    Yin, Peng; Li, Jing-Sheng; Kernkamp, Willem A; Tsai, Tsung-Yuan; Baek, Seung-Hoon; Hosseini, Ali; Lin, Lin; Tang, Peifu; Li, Guoan

    2017-09-08

    Numerous studies have reported on the tibiofemoral articular cartilage contact kinematics, however, no data has been reported on the articular cartilage geometry at the contact area. This study investigated the in-vivo tibiofemoral articular cartilage contact biomechanics during a dynamic step-up motion. Ten healthy subjects were imaged using a validated magnetic resonance and dual fluoroscopic imaging technique during a step-up motion. Three-dimensional bone and cartilage models were constructed from the magnetic resonance images. The cartilage contact along the motion path was analyzed, including cartilage contact location and the cartilage surface geometry at the contact area. The cartilage contact excursions were similar in anteroposterior and mediolateral directions in the medial and lateral compartments of the tibia plateau (P>0.05). Both medial and lateral compartments were under convex (femur) to convex (tibia) contact in the sagittal plane, and under convex (femur) to concave (tibia) contact in the coronal plane. The medial tibial articular contact radius was larger than the lateral side in the sagittal plane along the motion path (P<0.001). These data revealed that both the medial and lateral compartments of the knee experienced convex (femur) to convex (tibia) contact in sagittal plane (or anteroposterior direction) during the dynamic step-up motion. These data could provide new insight into the in-vivo cartilage contact biomechanics research, and may provide guidelines for development of anatomical total knee arthroplasties that are aimed to reproduce normal knee joint kinematics. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. The distribution of cartilage oligomeric matrix protein (COMP) in equine carpal articular cartilage and its variation with exercise and cartilage deterioration.

    PubMed

    Murray, R C; Smith, R K; Henson, F M; Goodship, A

    2001-09-01

    Based on previous studies where tendons receiving the most load have been shown to have the highest levels of cartilage oligomeric matrix protein (COMP), we hypothesized that COMP distribution in articular cartilage may be influenced by mechanical loading. This investigation aimed (a) to describe the pattern of COMP immunoreactivity in middle carpal joint cartilage of two-year-old Thoroughbred horses; (b) to determine topographical variations; (c) to compare high (group 1) and low (group 2) intensity training and (d) to describe COMP immunoreactivity at sites with early osteoarthritis. Group 1 (n =6) underwent a 19 week high-intensity treadmill training programme and group 2 (n =6) were given daily walking until euthanasia. Dorsal and palmar sites on radial and third carpal articular surfaces were prepared. Immunohistochemistry was performed with polyclonal rabbit anti-equine COMP antiserum using a biotin-streptavidin/peroxidase method. Results showed: (a) intracellular immunoreactivity was present in all cartilage zones, but the distribution of COMP staining within the matrix varied between cartilage zones; (b) differences in distribution between sites were not observed, but total COMP levels in exercised horses (n =2) did vary between sites with dorsal sites containing less COMP than palmar sites on the radial, intermediate and third carpal lateral facet; (c) group 1 cartilage showed marked interterritorial distribution in the deep layer compared to group 2 where staining was more generalized throughout the matrix and (d) fibrillated cartilage showed increased local immunoreactivity in the matrix. These findings demonstrate zonal variations in equine COMP distribution which may be influenced by loading. Copyright 2001 Harcourt Publishers Ltd.

  5. Subchondral bone changes and the impacts on joint pain and articular cartilage degeneration in osteoarthritis.

    PubMed

    Yu, Degang; Xu, Jiawei; Liu, Fengxiang; Wang, Xiaoqing; Mao, Yuanqing; Zhu, Zhenan

    2016-01-01

    Subchondral bone has received increasing attention in both basic and clinical research on osteoarthritis (OA). Subchondral bone in OA presents abnormalities in structure, biochemical composition, biomechanics and cellular function. Overall, subchondral bone mainly shows bone resorption in early OA and bone formation in late OA. More and more evidence suggests that abnormalities in subchondral bone of OA promote joint pain generation and articular cartilage degeneration. Inhibition or amelioration of subchondral bone abnormalities can reduce joint pain and can delay cartilage degeneration; thus, subchondral bone-targeted treatment promises to be a new treatment approach for OA. The pathological changes and the role of subchondral bone in OA still require further investigation.

  6. Streaming potentials: a sensitive index of enzymatic degradation in articular cartilage.

    PubMed

    Frank, E H; Grodzinsky, A J; Koob, T J; Eyre, D R

    1987-01-01

    Under physiological conditions, the extracellular matrix of articular cartilage contains a high fixed-charge density, associated with its ionized proteoglycan (PG) molecules. Compression of the highly charged cartilage matrix within the physiologic range leads to the production of electrical streaming potentials. We observed significant changes in the potential response due to chemical modifications of the matrix, such as extraction of PG and glycosaminoglycan (GAG) moieties using chondroitinase-ABC adn trypsin. The streaming potential was a sensitive index of the degradative loss of these matrix constituents and of the kinetics of the enzymatic degradative process.

  7. 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.

  8. 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

  9. Computational biomechanics of articular cartilage of human knee joint: effect of osteochondral defects.

    PubMed

    Shirazi, R; Shirazi-Adl, A

    2009-11-13

    Articular cartilage and its supporting bone functional conditions are tightly coupled as injuries of either adversely affects joint mechanical environment. The objective of this study was set to quantitatively investigate the extent of alterations in the mechanical environment of cartilage and knee joint in presence of commonly observed osteochondral defects. An existing validated finite element model of a knee joint was used to construct a refined model of the tibial lateral compartment including proximal tibial bony structures. The response was computed under compression forces up to 2000 N while simulating localized bone damage, cartilage-bone horizontal split, bone overgrowth and absence of deep vertical collagen fibrils. Localized tibial bone damage increased overall joint compliance and substantially altered pattern and magnitude of contact pressures and cartilage strains in both tibia and femur. These alterations were further exacerbated when bone damage was combined with base cartilage split and absence of deep vertical collagen fibrils. Local bone boss markedly changed contact pressures and strain patterns in neighbouring cartilage. Bone bruise/fracture and overgrowth adversely perturbed the homeostatic balance in the mechanical environment of articulate cartilage surrounding and opposing the lesion as well as the joint compliance. As such, they potentially contribute to the initiation and development of post-traumatic osteoarthritis.

  10. 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.

  11. A Biomechanical Triphasic Approach to the Transport of Nondilute Solutions in Articular Cartilage

    PubMed Central

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

    2009-01-01

    Abstract 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. PMID:20006942

  12. Effect of articular cartilage proteoglycan depletion on high frequency ultrasound backscatter.

    PubMed

    Pellaumail, B; Watrin, A; Loeuille, D; Netter, P; Berger, G; Laugier, P; Saïed, A

    2002-07-01

    To study the effect of variations of articular cartilage proteoglycans (PG) on high-frequency ultrasound backscatter. The study was performed on patellar cartilages of immature and mature rats (N=36). The variation of PG content was induced by enzyme digestion. Control and treated cartilages were explored in vitro using a 55MHz scanning acoustic microscopy, then assessed by histology for the fibrillar collagen organization analysis. The variations of proteoglycan and collagen content were evaluated. Thickness measurements performed on both B-scan images and histologic sections were compared. Ultrasonic radio-frequency signals reflected by the cartilage surface and backscattered from its internal matrix were processed to estimate the integrated reflection coefficient (IRC) and apparent integrated backscatter (AIB). Although hyaluronidase treatment of immature and mature cartilages removed approximately 50% of the proteoglycans, the echogenicity level of ultrasound images of degraded cartilages was similar to that of controls. IRC and AIB parameters did not significantly vary. Histologic sections of degraded cartilage displayed no change in collagen fiber organization. The thickness mean values measured by ultrasound in PG-depleted groups were significantly higher than in controls, whereas no significant difference in thickness was detected by histological measurement. The increase in cartilage thickness may potentially be explained by a decrease of speed of sound in PG-depleted cartilages that is more likely subsequent to an increase of water content. Current results indicate that PG depletion has no significant effect on high frequency ultrasound backscattered from rat patellar cartilage. Ultrasound may provide information about variations of PG content via speed of sound measurement. Copyright 2002 OsteoArthritis Research Society International. Published by Elsevier Science Ltd. All rights reserved.

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

    PubMed Central

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

    2017-01-01

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

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

    PubMed

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

    2017-06-28

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

  15. 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.

  16. Articular Cartilage Repair Through Muscle Cell-Based Tissue Engineering

    DTIC Science & Technology

    2010-03-01

    Histologic scores were compared using the Kruskal- Wallis test. P values less than 0.05 were considered significant. RESULTS Macroscopic and histologic findings...2005;20: 2017 –27. 29. Pritzker KP, Gay S, Jimenez SA, Ostergaard K, Pelletier JP, Revell PA, et al. Osteoarthritis cartilage histopathology: grading and...analysis of variance except for comparisons of histologic scores, which were per- formed by Kruskal- Wallis analysis. Post hoc analysis was performed with

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

    NASA Astrophysics Data System (ADS)

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

    1996-12-01

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

  18. Viscoelasticity of articular cartilage: Analysing the effect of induced stress and the restraint of bone in a dynamic environment.

    PubMed

    Lawless, Bernard M; Sadeghi, Hamid; Temple, Duncan K; Dhaliwal, Hemeth; Espino, Daniel M; Hukins, David W L

    2017-07-27

    The aim of this study was to determine the effect of the induced stress and restraint provided by the underlying bone on the frequency-dependent storage and loss stiffness (for bone restraint) or modulus (for induced stress) of articular cartilage, which characterise its viscoelasticity. Dynamic mechanical analysis has been used to determine the frequency-dependent viscoelastic properties of bovine femoral and humeral head articular cartilage. A sinusoidal load was applied to the specimens and out-of-phase displacement response was measured to determine the phase angle, the storage and loss stiffness or modulus. As induced stress increased, the storage modulus significantly increased (p < 0.05). The phase angle decreased significantly (p < 0.05) as the induced stress increased; reducing from 13.1° to 3.5°. The median storage stiffness ranged from 548N/mm to 707N/mm for cartilage tested on-bone and 544N/mm to 732N/mm for cartilage tested off-bone. On-bone articular cartilage loss stiffness was frequency independent (p > 0.05); however, off-bone, articular cartilage loss stiffness demonstrated a logarithmic frequency-dependency (p < 0.05). In conclusion, the frequency-dependent trends of storage and loss moduli of articular cartilage are dependent on the induced stress, while the restraint provided by the underlying bone removes the frequency-dependency of the loss stiffness. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  19. 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

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

    PubMed Central

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

    2016-01-01

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

  1. 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.

  2. 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

  3. Bone turnover and articular cartilage differences localized to subchondral cysts in knees with advanced osteoarthritis.

    PubMed

    Chen, Y; Wang, T; Guan, M; Zhao, W; Leung, F-K-L; Pan, H; Cao, X; Guo, X E; Lu, W W

    2015-12-01

    To investigate changes in bone structure, turnover, and articular cartilage localized in subchondral bone cyst (SBC) regions associated with knee osteoarthritis (OA). Tibial plateaus (n = 97) were collected from knee OA patients during total knee arthroplasty (TKA). SBCs were identified using micro-computed tomography, and the specimens were divided into non-cyst (n = 25) and bone cyst (n = 72) groups. Microstructure of subchondral bone was assessed using bone volume fraction (BV/TV), trabecular number (Tb.N), structure model index (SMI) and bone mineral density (BMD). In bone cyst group, the cyst subregion, which contained at least one cyst, and the peri-cyst subregion, which contained no cysts, were further selected for microstructure analysis. Articular cartilage damage was estimated using the Osteoarthritis Research Society International (OARSI) score. The numbers of TRAP(+) osteoclasts, Osterix(+) osteoprogenitors, Osteocalcin(+) osteoblasts and expression of SOX9 were evaluated by immunohistochemistry. Bone cyst group presented higher BV/TV, Tb.N and SMI at subchondral bone than non-cyst group. Furthermore, cyst subregion displayed increased BV/TV and Tb.N but lower BMD and SMI than peri-cyst subregion. Histology revealed a higher OARSI score in bone cyst group. SBC exhibited a weak relationship with BV/TV, etc. The numbers of TRAP(+) osteoclasts, Osterix(+) osteoprogenitors, Osteocalcin(+) osteoblasts and expression of SOX9, were higher in bone cyst group. SBCs within knee OA are characterized by focally increased bone turnover, altered bone structure and more severe articular cartilage damage. The increased bone turnover possibly contributes to altered bone structure localized in SBC areas, and thus aggravates articular cartilage degeneration. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  4. Ultrasound elastomicroscopy using water jet and osmosis loading: potentials for assessment for articular cartilage.

    PubMed

    Zheng, Yong-Ping; Lu, Min-Hua; Wang, Qing

    2006-12-22

    Research in elasticity imaging typically relies on 1-10 MHz ultrasound. Elasticity imaging at these frequencies can provide strain maps with a resolution in the order of millimeters, but this is not sufficient for applications to skin, articular cartilage, or other fine structures. In this paper, we introduced two methods of ultrasound elastomicroscopy using water jet and osmosis loading for imaging the elasticity of biological soft tissues with high resolutions. In the first system, the specimens were compressed using water jet compression. A water jet was used to couple a focused 20 MHz ultrasound beam into the specimen and meanwhile served as a "soft" indenter. Because there was no additional attenuation when propagating from the ultrasound transducer to the specimen, the ultrasound signal with high signal-to-noise ratio could be collected from the specimens simultaneously with compressing process. The compression was achieved by adjusting the water flow. The pressure measured inside the water pipe and that on the specimen surface was calibrated. This system was easily to apply C-scan over sample surfaces. Experiments on the phantoms showed that this water jet indentation method was reliable to map the tissue stiffness distribution. Results of 1D and 2D scanning on phantoms with different stiffness are reported. In the second system, we used osmotic pressure caused by the ion concentration change in the bathing solutions for the articular cartilage to deform them. When bovine articular cartilage specimens were immerged in solutions with different salt concentration, a 50 MHz focused ultrasound beam was used to monitor the dynamic swelling or shrinkage process. Results showed that the system could reliably map the strain distribution induced by the osmotic loading. We extract intrinsic layered material parameters of the articular cartilage using a triphasic model. In addition to biological tissues, these systems have potential applications for the assessment of

  5. Effect of highly purified capsaicin on articular cartilage and rotator cuff tendon healing: An in vivo rabbit study.

    PubMed

    Friel, Nicole A; McNickle, Allison G; DeFranco, Michael J; Wang, FanChia; Shewman, Elizabeth F; Verma, Nikhil N; Cole, Brian J; Bach, Bernard R; Chubinskaya, Susan; Kramer, Susan M; Wang, Vincent M

    2015-12-01

    Highly purified capsaicin has emerged as a promising injectable compound capable of providing sustained pain relief following a single localized treatment during orthopedic surgical procedures. To further assess its reliability for clinical use, the potential effect of highly purified capsaicin on articular cartilage metabolism as well as tendon structure and function warrants clarification. In the current study, rabbits received unilateral supraspinatus transection and repair with a single 1 ml injection of capsaicin (R+C), PEG-only placebo (R+P), or saline (R+S) into the glenohumeral joint (GHJ). An additional group received 1 ml capsaicin onto an intact rotator cuff (I+C). At 18 weeks post-op, cartilage proteoglycan (PG) synthesis and content as well as cell viability were similar (p>0.05) across treatment groups. Biomechanical testing revealed no differences (p>0.05) among tendon repair treatment groups. Similarly, histologic features of both cartilage and repaired tendons showed minimal differences across groups. Hence, in this rabbit model, a single injection of highly purified capsaicin into the GHJ does not induce a deleterious response with regard to cartilage matrix metabolism and cell viability, or rotator cuff healing. These data provide further evidence supporting the use of injectable, highly purified capsaicin as a safe alternative for management of postoperative pain following GHJ surgery. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  6. Iron oxide labelling of human mesenchymal stem cells in collagen hydrogels for articular cartilage repair.

    PubMed

    Heymer, Andrea; Haddad, Daniel; Weber, Meike; Gbureck, Uwe; Jakob, Peter M; Eulert, Jochen; Nöth, Ulrich

    2008-04-01

    For the development of new therapeutical cell-based strategies for articular cartilage repair, a reliable cell monitoring technique is required to track the cells in vivo non-invasively and repeatedly. We present a systematic and detailed study on the performance and biological impact of a simple and efficient labelling protocol for human mesenchymal stem cells (hMSCs). Commercially available very small superparamagnetic iron oxide particles (VSOPs) were used as magnetic resonance (MR) contrast agent. Iron uptake via endocytosis was confirmed histologically with prussian blue staining and quantified by mass spectrometry. Compared with unlabelled cells, VSOP-labelling did neither influence the viability nor the proliferation potential of hMSCs. Furthermore, iron incorporation did not affect hMSCs in undergoing adipogenic, osteogenic or chondrogenic differentiation, as demonstrated histologically and by gene expression analyses. The efficiency of the labelling protocol was assessed with high-resolution MR imaging at 11.7T. VSOP-labelled hMSCs were visualised in a collagen type I hydrogel, which is in clinical use for matrix-based articular cartilage repair. The presence of VSOP-labelled hMSCs was indicated by distinct hypointense spots in the MR images, as a result of iron specific loss of signal intensity. In summary, this labelling technique has great potential to visualise hMSCs and track their migration after transplantation for articular cartilage repair with MR imaging.

  7. [An automatic subregion delineation method for T2 measurement of articular cartilage in the knee].

    PubMed

    Zhong, Zhihui; Yu, Taihui; Wang, Lei; Yang, Wei; Feng, Meiyan; Lu, Zhentai; Chen, Wufan; Feng, Yanqiu

    2013-06-01

    To propose a new method for automatic segmentation of manually determined knee articular cartilage into 9 subregions for T2 measurement. The middle line and normal line were automatically obtained based on the outline of articular cartilage manually drawn by experienced radiologists. The region of articular cartilage was then equidistantly divided into 3 layers along the direction of the normal line, and each layer was further equidistantly divided into 3 segments along the direction of the middle line. Finally the mean T2 value of each subregion was calculated. Bland-Altman analysis was used to evaluate the agreement between the proposed and manual subregion segmentation methods. The 95% limits of agreement of manual and automatic methods ranged from -3.04 to 3.20 ms, demonstrating a narrow 95% limits of agreement (less than half of the minimum average). The coefficient of variation between the manual and proposed subregion methods was 4.04%. The proposed subregion segmentation method shows a good agreement with the manual segmentation method and minimizes potential subjectivity of the manual method.

  8. 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

  9. 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.

  10. The potential of human allogeneic juvenile chondrocytes for restoration of articular cartilage.

    PubMed

    Adkisson, H Davis; Martin, James A; Amendola, Richard L; Milliman, Curt; Mauch, Kelsey A; Katwal, Arbindra B; Seyedin, Mitchell; Amendola, Annuziato; Streeter, Philip R; Buckwalter, Joseph A

    2010-07-01

    Donor-site morbidity, limited numbers of cells, loss of phenotype during ex vivo expansion, and age-related decline in chondrogenic activity present critical obstacles to the use of autologous chondrocyte implantation for cartilage repair. Chondrocytes from juvenile cadaveric donors may represent an alternative to autologous cells. Hypothesis/ The authors hypothesized that juvenile chondrocyte would show stronger and more stable chondrogenic activity than adult cells in vitro and that juvenile cells pose little risk of immunologic incompatibility in adult hosts. Controlled laboratory study. Cartilage samples were from juvenile (<13 years old) and adult (>13 years old) donors. The chondrogenic activity of freshly isolated human articular chondrocytes and of expanded cells after monolayer culture was measured by proteoglycan assay, gene expression analysis, and histology. Lymphocyte proliferation assays were used to assess immunogenic activity. Proteoglycan content in neocartilage produced by juvenile chondrocytes was 100-fold higher than in neocartilage produced by adult cells. Collagen type II and type IX mRNA in fresh juvenile chondrocytes were 100- and 700-fold higher, respectively, than in adult chondrocytes. The distributions of collagens II and IX were similar in native juvenile cartilage and in neocartilage made by juvenile cells. Juvenile cells grew significantly faster in monolayer cultures than adult cells (P = .002) and proteoglycan levels produced in agarose culture was significantly higher in juvenile cells than in adult cells after multiple passages (P < .001). Juvenile chondrocytes did not stimulate lymphocyte proliferation. These results document a dramatic age-related decline in human chondrocyte chondrogenic potential and show that allogeneic juvenile chondrocytes do not stimulate an immunologic response in vivo. Juvenile human chondrocytes have greater potential to restore articular cartilage than adult cells, and may be transplanted without the

  11. THE POTENTIAL OF HUMAN ALLOGENEIC JUVENILE CHONDROCYTES FOR RESTORATION OF ARTICULAR CARTILAGE

    PubMed Central

    Adkisson, H. Davis; Martin, James A.; Amendola, Richard L.; Milliman, Curt; Mauch, Kelsey A.; Katwal, Arbindra B.; Seyedin, Mitchell; Amendola, Annuziato; Streeter, Philip R.; Buckwalter, Joseph A.

    2013-01-01

    Background Donor site morbidity, limited numbers of cells, loss of phenotype during ex vivo expansion, and age-related decline in chondrogenic activity present critical obstacles to the use of autologous chondrocyte implantation for cartilage repair. Chondrocytes from juvenile cadaveric donors may represent an alternative to autologous cells. Hypothesis/Purpose The authors hypothesized that juvenile chondrocyte would show stronger and more stable chondrogenic activity than adult cells in vitro and that juvenile cells pose little risk of immunologic incompatibility in adult hosts. Study Design Controlled laboratory study. Methods Cartilage samples were from juvenile (<13 years old) and adult (> 13 years old) donors. The chondrogenic activity of freshly isolated human articular chondrocytes and of expanded cells after monolayer culture was measured by proteoglycan assay, gene expression analysis, and histology. Lymphocyte proliferation assays were used to assess immunogenic activity. Results Proteoglycan content in neocartilage produced by juvenile chondrocytes was 100-fold higher than in neocartilage produced by adult cells. Collagen type II and type IX mRNAs in fresh juvenile chondrocytes were 100- and 700-fold higher, respectively, than in adult chondrocytes. The distributions of collagens II and IX were similar in native juvenile cartilage and in neocartilage made by juvenile cells. Juvenile cells grew significantly faster in monolayer cultures than adult cells (p = 0.002) and proteoglycan levels produced in agarose culture was significantly higher in juvenile cells than in adult cells after multiple passages (p < 0.001). Juvenile chondrocytes did not stimulate lymphocyte proliferation. Conclusions These results document a dramatic age related decline in human chondrocyte chondrogenic potential and show that allogeneic juvenile chondrocytes do not stimulate an immunologic response in vivo. Clinical Relevance Juvenile human chondrocytes have greater potential to

  12. Cytotoxicity of local anesthetics to rats' articular cartilage: an experimental study.

    PubMed

    Beyzadeoğlu, Tahsin; Torun Köse, Gamze; Ekinci, Işın D; Bekler, Halil; Yilmaz, Cemil

    2012-01-01

    The aim of this study was to evaluate the effects of both in vivo and in vitro bupivacaine, levobupivacaine and tramadol on articular cartilage and chondrocytes in experimental rat models. Thirty mature Sprague Dawley rats weighing 230-300 g were randomized into 3 groups. Bupivacaine (Group 1), levobupivacaine (Group 2) and tramadol (Group 3) were injected into the right knee joints and a physiological 0.9% saline into the left. From each group, 5 rats were executed 48 hours following drug administration after 5 and 10 days. The specimens were fixed, decalcified and stained with hematoxylin & eosin and toluidine blue. All samples were histopathologically evaluated according to the recommendation of ICRS' osteoarthritis and cartilage histopathology grading and staging system. Articular cartilage cells of the rats were cultured and seeded into cell culture flasks. Cartilage cell seeded samples (104 cells/ml) were incubated in three different anesthetic agents (0.5%); bupivacaine, levobupivacaine, and tramadol, respectively. CellTiter 96(®) Non-Radioactive Cell Proliferation (MTS) assay was used to determine the cell density on the samples. Statistically significant higher OARSI grades and OA stage and scores were detected when comparing the group injected with levobupivacaine and executed after 10 days with the levobupivacaine injected group killed after 48 hours (p<0.01 [p=0.008]). Although, statistical analysis could not be done due to insufficient number of samples in the in vitro part of the experiment, it can be concluded that tramadol is cytotoxic to rat chondrocyte in vitro after 30 min of exposure. Additionally, cell numbers in both the bupivacaine and levobupivacaine treated wells showed decrease throughout 15, 30 and 60 minute exposures. Although chondrotoxicity of bupivacaine was less harmful than levobupivacaine and tramadol, these findings suggest that local anesthetics may negatively affect articular cartilage and chondrocytes.

  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. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. Autologous nasal chondrocytes delivered by injectable hydrogel for in vivo articular cartilage regeneration.

    PubMed

    Chen, Wenliang; Li, Changhua; Peng, Maoxiu; Xie, Bingju; Zhang, Lei; Tang, Xiaojun

    2017-08-16

    Cell based tissue engineering serves as a promising strategy for articular cartilage repair, which remains a challenge both for researchers and clinicians. The aim of this research was to assess the potential of autologous nasal chondrocytes (NCs) combined with alginate hydrogel as injectable constructs for rabbit articular cartilage repair. Autologous nasal chondrocytes were isolated from rabbit nasal septum, expanded either on monolayer or in 3D alginate hydrogel. In vitro, DNA quantification revealed that NCs can proliferate stable in 3D alginate matrix, but slower than that cultured in monolayer. Further, a higher synthesis rate of glycosaminoglycans (GAGs) was detected by GAG measurement in 3D alginate culture. Gene expression analysis at different time point (day 1, 7, 14) showed that 3D culture of NCs in alginate up-regulated chondrogenic markers (Col2A1, ACAN SOX9), meanwhile down-regulated dedifferentiation related gene (Col1A1). In vivo, autologous nasal chondrocytes combined with alginate hydrogel were used for repairing rabbit knee osteochondral defect (Alg + NC group). Histological staining indicated that Alg + NC group obtained superior and more hyaline-like repaired tissue both at 3 and 6 months after surgery. Mechanical analysis showed that the repaired tissue in the Alg + NC group possessed similar mechanical properties to the native cartilage. In conclusion, nasal chondrocytes appeared to be a very promising seed cell source for cartilage tissue engineering, and alginate hydrogel can serve as suitable delivery system.

  1. 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.

  2. The use of active shape models for making thickness measurements of articular cartilage from MR images.

    PubMed

    Solloway, S; Hutchinson, C E; Waterton, J C; Taylor, C J

    1997-06-01

    Previously reported studied to quantify articular cartilage have used labor-intensive manual or semi-automatic data-driven techniques, demonstrating high accuracy and precision. However, none has been able to automate the segmentation process. This paper describes a fast, automatic, model-based approach to segmentation and thickness measurement of the femoral cartilage in 3D T1-weighted images using active shape models (ASMs). Systematic experiments were performed to assess the accuracy and precision of the technique with in vivo images of both normal and abnormal knees. Segmentation accuracy was determined by comparing the results of the segmentation with the boundaries delineated by a radiologist. The mean error in locating the boundary was 0.57 pixels. To assess the precision of the measurement technique, the mean thickness of the femoral cartilage was calculated for repeated scans of five healthy volunteers. A mean coefficient of variation (CV) of 2.8% was obtained for the thickness measurements.

  3. A feasibility study for evaluation of mechanical properties of articular cartilage with a two-electrode electrical impedance method.

    PubMed

    Morita, Yusuke; Kondo, Hideo; Tomita, Naohide; Suzuki, Shigehiko

    2012-05-01

    Since articular cartilage has important mechanical properties such as load-bearing, shock absorption and lubrication for activities in daily life, it is important to evaluate the mechanical properties of repaired cartilage in terms of whether those properties are the same as those of natural cartilage. The purpose of this study was to investigate the effectiveness of an electrical impedance method for quantitatively measuring the mechanical properties of cartilage. Cartilage specimens were harvested from porcine knee joint, and two kinds of enzyme-treated cartilages were prepared to investigate the correlation between mechanical and electrical properties resulting from changes in the structure of the extracellular matrix. Collagenase solution and hyaluronidase solution were used to digest the collagen fibril and proteoglycan, respectively. Electrical impedance measurement, indentation test and biochemical analysis were carried out for the enzyme-treated cartilages. The water content increased with enzyme treatment time, and the permeability of the treated cartilages increased with decreasing glycosaminoglycan content for both types of enzyme-treated cartilages. The aggregate modulus and the electrical resistivity for both types of enzyme-treated cartilages decreased with increasing permeability after 12-h treatment. The aggregate modulus and the electrical resistivity for both types of treated cartilages decreased with increasing water content and permeability after 24-h treatment. The electrical resistivity and the aggregate modulus of articular cartilage depended not only on the water content, but also on the permeability, and the electrical resistivity for both types of enzyme-treated cartilages was found to be significantly linearly correlated with the aggregate modulus. These results showed that the aggregate modulus of articular cartilage can be estimated by measuring its electrical impedance.

  4. 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

  5. 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

  6. 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.

  7. Effect of biomechanical stress on endogenous antioxidant networks in bovine articular cartilage.

    PubMed

    Issa, Rita; Boeving, Michael; Kinter, Michael; Griffin, Timothy M

    2017-09-11

    Mechanosensitve pathways in chondrocytes are essential for maintaining articular cartilage homeostasis. Traumatic loading increases cartilage oxidation and causes cell death and osteoarthritis. However, sub-lethal doses of the pro-oxidant molecule tert-Butyl hydroperoxide (tBHP) protects against loading-induced chondrocyte death. We hypothesized that compressive cyclic loading at moderate strains (<20%) causes sub-lethal cartilage oxidation that induces an adaptive increase in the endogenous antioxidant defense network. We tested this hypothesis by subjecting healthy bovine articular cartilage explants to in vitro static or cyclic (1 Hz) compressive loading at 50kPa (15% strain, "physiologic") versus 300kPa (40% strain, "hyper-physiologic") for 12 hours per day for 2 days. We also treated unloaded explants with 100µM tBHP for 12 hours per day for 2 days to differentiate between biomechanical and chemical pro-oxidant stimulation. All loading conditions induced glutathione oxidation relative to unloaded controls, but only the 50kPa cyclic loading condition increased total glutathione content (2-fold). This increase was associated with a greater expression of glutamate-cysteine ligase, the rate-limiting step in glutathione synthesis, compared to 300kPa cyclic loading. 50kPa cyclic loading also increased the expression of superoxide dismutase-1 and peroxiredoxin-3. Like 50kPa loading, tBHP treatment also increased total glutathione content. However, tBHP treatment and 50kPa cyclic loading differed in their effect on the expression of genes regulating antioxidant defense and cartilage matrix synthesis and degradation. These findings suggest that glutathione metabolism is a mechanosensitive antioxidant defense pathway in chondrocytes and that intermittent pro-oxidant treatment alone is insufficient to account for all changes in mediators of cartilage homeostasis associated with cyclic loading. This article is protected by copyright. All rights reserved. This article

  8. An injectable cellulose-based hydrogel for the transfer of autologous nasal chondrocytes in articular cartilage defects.

    PubMed

    Vinatier, C; Gauthier, O; Fatimi, A; Merceron, C; Masson, M; Moreau, A; Moreau, F; Fellah, B; Weiss, P; Guicheux, J

    2009-03-01

    Articular cartilage has a low capacity for spontaneous repair. To promote the repair of this tissue, the transfer of autologous chondrocytes using a three-dimensional matrix appears promising. In this context, the aim of the present work was to investigate the potential use of autologous rabbit nasal chondrocytes (RNC) associated with an injectable self-setting cellulose-based hydrogel (Si-HPMC). Firstly, the influence of Si-HPMC on chondrocytic phenotype was investigated by real-time PCR for specific chondrocyte markers (type II collagen and aggrecan) and type I collagen. Thereafter, autologous RNC were amplified in vitro for 4 weeks before transplantation with Si-HPMC into a rabbit articular cartilage defect followed by analysis 6 weeks later. Implants were histologically characterized for the presence of sulfated GAG and type II collagen. Transcripts analysis indicated that dedifferentiated RNC recovered expression of the main chondrocytic markers after in vitro three-dimensional culture within Si-HPMC. Histological analysis of autologous RNC transplanted in an articular cartilage defect revealed the formation of repair tissue with a histological organization similar to that of healthy articular cartilage. In addition, immunohistological analysis of type II collagen suggested that the repair tissue was a hyaline-like cartilage. Si-HPMC hydrogel associated with nasal chondrocytes therefore appears a promising injectable tissue engineering device for the repair of articular cartilage.

  9. 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

  10. 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.

  11. Cartilage biomarkers in hemodialysis patients and the effect of beta2-microglobulin on articular chondrocytes.

    PubMed

    Sunk, I-G; Demetriou, D; Szendroedi, J; Amoyo, L; Raffetseder, A; Hörl, W H; Sunder-Plassmann, G; Smolen, J S; Bobacz, K

    2008-11-01

    Dialysis-related amyloidosis (DRA) is a severe complication of maintenance hemodialysis (HD). Given the predominant deposition of beta(2)-microglobulin (beta2m) fibrils on articular cartilage in early DRA, we investigated the significance of beta2m and its relationship to distinct cartilage biomarkers in early DRA diagnosis in HD patients. Furthermore, we assessed the effects of beta2m on articular chondrocytes in vitro. Serum samples from 133 patients were collected before and after HD. Type II collagen cleavage product (C2C), procollagen II c-propeptide (CPII), aggrecan chondroitin sulfate 846 epitope (CS-486) and cartilage oligomeric matrix protein (COMP) levels were determined by enzyme-linked immunosorbent assay. Primary bovine articular chondrocytes were cultured as monolayers and incubated with beta2m at 1.5mg/l and 20mg/l. Cartilage glucosaminoglycan synthesis was measured by [(35)S]sulfate incorporation. mRNA expression of interleukin (IL)-1beta, matrix metalloproteinases (MMPs)-3 and -9 was measured by reverse-transcriptase polymerase chain reaction (RT-PCR). Incubation with beta2m at 20mg/l significantly decreased matrix biosynthesis. PCR analysis revealed an increase of IL-1beta, as well as MMPs-3 and -9 on the mRNA level. C2C/CPII, CS-486 and COMP levels were increased only in a subset of patients without a significant correlation with beta2m concentrations. A subgroup analysis elucidated an increase in type II collagen degradation during the first years of HD, as shown by the elevation of C2C/CPII ratio. beta2m exerted anti-anabolic effects on articular chondrocytes in vitro and might be involved in cartilage degradation in HD patients. beta2m serum levels, however, did not reflect cartilage degradation in DRA. The assessment of C2C/CPII, CS-486 or COMP concentrations apparently has minor relevance in DRA diagnosis in HD patients. However, the increased type II collagen breakdown within 5 years after HD onset possibly mirrors the early stages of DRA

  12. Symptoms and function in patients with articular cartilage lesions in 1,000 knee arthroscopies.

    PubMed

    Solheim, Eirik; Krokeide, Arne Magnus; Melteig, Peder; Larsen, Allan; Strand, Torbjørn; Brittberg, Mats

    2016-05-01

    Focal chondral lesions of the knee are commonly occurring. A lot is known about their frequency, size and localisation in arthroscopic series, but less about the symptoms they elicit and little about how the arthroscopic findings and symptoms correlate. The purposes of the present study included to investigate the relationship between articular cartilage lesion factors and patient factors, and to compare the symptoms and function of cartilage lesion patients to those of patients with a deficient ACL. A prospective registration was conducted of preoperative data including Lysholm knee score and perioperative findings in 1,000 consecutive patients undergoing an arthroscopic procedure of the knee-including microfracture of articular cartilage defects and ACL reconstructions. Chondral or osteochondral lesions were found in 57 % of the arthroscopies. The mean Lysholm score in this subgroup was 55. The mean Lysholm score was significantly lower in women (50, SD 19) compared to men (59, SD 18, p < 0.001). Among the chondral lesion factors, only kissing (vs. non-kissing) lesions and multiple (vs. single) lesions influenced symptoms and function to a more than negligible degree. Microfracture in one or two articular cartilage defects was performed in 187 patients. The microfracture group had a significant lower mean Lysholm score (54, SD 18) than a group of patients (N = 71) undergoing ACL reconstruction group (67, SD 17, p < 0.001). The study confirms that articular cartilage lesions are both common and cumbersome. Women seem to have more problems than men, whereas chondral lesion factors-such as localisation and size-seem to influence symptoms and function to a small degree. These aspects should be addressed when designing outcome studies, and should also be of interest to the orthopaedic surgeon-in the day-by-day clinical work. When treating these patients, our prime focus need to be on knee function rather than the cartilage defect as the relationship between the

  13. 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.

  14. 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.

  15. Assessment of rat articular cartilage maturation using 50-MHz quantitative ultrasonography.

    PubMed

    Chérin, E; Saïed, A; Pellaumail, B; Loeuille, D; Laugier, P; Gillet, P; Netter, P; Berger, G

    2001-02-01

    The objective was to assess the relationship between maturation-related structural changes of articular cartilage and variations of acoustic parameters estimated using high frequency ultrasonography. Patellae taken from 48 immature Wistar male rats and divided into six age groups (from five to 11 weeks old) were explored in vitro using 50-MHz scanning acoustic microscopy, then assessed by histology for the analysis of the cartilage cell distribution and fibrillar collagen organization. The variation of cartilage proteoglycan and collagen content with age was evaluated. Thickness measurements performed on both B-scan images and histologic sections were compared. Ultrasonic radiofrequency signals reflected by the cartilage surface and backscattered from its internal matrix were processed to estimate the integrated reflection coefficient (IRC) and apparent integrated backscatter (AIB). One-way ANOVA indicated that acoustic parameters and thickness change significantly (P < 0.05) as the animal matures because of age-related changes in cartilage composition and morphology. A moderate correlation was found between IRC and the animal age. The parameter decreased slightly but significantly over time. However, a good correlation was observed between the rat age and the AIB, which decreased significantly over time. The parameter variation was mostly related to the changes in collagen fiber orientation, and/or to a change in cell size, density and organization. Current results indicate that acoustic properties of cartilage are affected by maturation-related cartilage changes. This suggests that high frequency ultrasonography may serve as a useful means for the investigation of cartilage matrix structural changes occurring under various clinical circumstances, like those observed during osteoarthritis, and for the evaluation of the efficacy of specific therapeutics. Copyright 2001

  16. 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

  17. 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.

  18. 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.

  19. Intra-articular injection of dexketoprofen in rat knee joint : Histopathologic assessment of cartilage & synovium

    PubMed Central

    Ekici, Aycan Guner; Akyol, Onat; Ekici, Murat; Sitilci, Tolga; Topacoglu, Hakan; Ozyuvaci, Emine

    2014-01-01

    Background & objectives: Effective pain control following outpatient surgical procedures is an important aspect of patient discharge. This study was carried out with an aim to investigate the histopathological effects of intra-articular dexketoprofen trometamol injection in knee joint on synovium and cartilage in an experimental rat model. Methods: In each of 40 rats, the right knee was designated as the study group and the left knee as the control group (NS group). Under aseptic conditions, 35 rats received an injection of 0.25 ml (6.25 mg) dexketoprofen trometamol into the right knee joint and an injection of 0.25 ml 0.9 per cent normal saline solution into the left knee joint. On the 1st, 2nd, 7th, 14th, and 21st days after intra-articular injection, rats in specified groups were sacrificed by intraperitoneal injection of 120 mg/kg sodium thiopental. Knee joints were separated and sectioned for histopathological examination. Inflammatory changes in the joints were recorded according to a grade scale. Results: No significant difference in terms of pathological changes both in synovium and cartilage was observed between the NS group and the study group on days 1, 2, 7, 14 and 21 after intra-articular injection of dexketoprofen or saline in the knee joint. Interpretation & conclusions: The findings showed no evidence of significant histopathological damage to the cartilage and synovia for a period up to 21 days following intra-articular administration of dexketoprofen trometamol in the knee joints of rats. PMID:25297355

  20. Direct Visualisation of the Depth-Dependent Mechanical Properties of Full-Thickness Articular Cartilage

    PubMed Central

    Szarko, Matthew; Xia, Yang

    2013-01-01

    Objective The structural anisotropy of articular cartilage controls its deformation response. As proteoglycans and collagen vary with depth, simple uniaxial compression results in inhomogeneous deformation with distinct depth-dependent mechanical properties. Investigations into depth-dependent mechanical properties of articular cartilage have previously required tissue modification after specimen isolation. Such modifications include histological processes, freezing, subchondral bone removal, and fluorescent staining that may alter the tissue, limiting in vivo applicability. Design Using a custom tissue-sectioning device, 0.1 mm thick unfixed, unstained, osetochondral samples were obtained. A customized apparatus loaded samples to 12.5, 24, and 29% compression in under a microscope with 10× magnification. Equilibrium load was measured after stress relaxation. Intra-tissue displacement was measured by tracing groups of cells between the different compression levels using a digital imaging program. Cell distance from the subchondral bone was measured to identify intra-tissue displacement and calculate strain. Results The results reveal that stress levels and intra-tissue displacement increased with greater tissue compression (p <0.05). Intra-tissue displacement decreased as depth from the articular surface increased (p<0.01). This occurred for each level of tissue compression. Overall compressive resistance is seen to increase with depth from the articular surface. Conclusions The current study identifies a method directly visualising and assessing the depth-dependent structural response to compression. The ability to avoid tissue modification after specimen isolation, allows this procedure to more closely approximate in vivo conditions and may provide an important method for analyzing the coordinated changes in cartilage composition and function due to ageing and disease. PMID:24416657

  1. A theoretical solution for the frictionless rolling contact of cylindrical biphasic articular cartilage layers.

    PubMed

    Ateshian, G A; Wang, H

    1995-11-01

    Previous studies have shown that interstitial fluid pressurization plays an important role in the load support mechanism of articular cartilage under normal step loading. These studies have demonstrated that interstitial fluid pressurization decreases with time if the applied load is maintained constant. In the present study, a theoretical solution is obtained for another common loading of articular cartilage, namely the contact of surfaces in rolling motion. Pure rolling of symmetrical frictionless cylindrical cartilage layers is analyzed under steady state. The linear biphasic model of Mow et al. [J. Biomech. Engng 102, 73-84 (1980)] is used to describe the mechanical response of articular cartilage. The solution of this contact problem reduces to simultaneously solving a set of four integral equations, akin to the dual integral problem of elastic contact. It is found that the solution is dependent on four non-dimensional parameters: Rh = Vb/HAk, W/2 mu b, R/b, and v, where V is the surface velocity, b the cartilage thickness, HA the aggregate modulus, mu the shear modulus, v Poisson's ratio, k the permeability, R the radius of cylindrical surfaces, and W the applied load per unit cylinder length. For Rh < 1, interstitial fluid pressurization is found to be negligible, and all the applied load is supported by the solid collagen-proteoglycan phase of the tissue, thus causing significant cartilage deformation. As Rh increases to a physiological level (Rh approximately 10(4)), interstitial fluid pressurization may support more than 90% of the total applied load, shielding the solid matrix from high effective stresses and reducing matrix strains and deformation. The protective effect of interstitial fluid pressurization is observed to increase with increasing joint congruence (R/b); similarly, as the applied load (W/2 mu b) is increased, a greater proportion of it is supported by the fluid. In degenerative cartilage, Rh may drop by one or more orders of magnitude

  2. Correlation of preoperative MRI and MRA with arthroscopically proven articular cartilage lesions of the elbow.

    PubMed

    Theodoropoulos, John S; Dwyer, Tim; Wolin, Preston M

    2012-09-01

    The purpose of this study was to evaluate the usefulness of magnetic resonance imaging (MRI) in detecting elbow articular cartilage injuries through comparison of preoperative MRI and magnetic resonance arthrography (MRA) with arthroscopic findings. Retrospective case analysis. Tertiary care orthopedic private practice. Consecutive series of 31 patients presenting with elbow pain and diagnosed at arthroscopy with articular cartilage defects of the elbow. All patients had a preoperative MRI or MRA using a 1.5 T magnet. Each patient had a systematic elbow arthroscopy, with careful inspection and recording of chondral injuries in 4 anatomical regions: capitellum, radius, trochlea, and ulna. Each MRI/MRA was then independently reviewed by 2 radiologists blinded to the arthroscopic findings. The sensitivity, specificity, negative predictive value, positive predictive value, and accuracy were calculated for MRI and MRI compared with arthroscopy as the gold standard, for each of the anatomical regions. The accuracy of MRI was 45% for chondral injuries of the radius, 65% for the capitellum, 20% for the ulna, and 30% for the trochlea. The accuracy of MRA was 45% for chondral injuries of the radius, 64% for the capitellum, 18% for the ulna, and 27% for the trochlea. We conclude that the ability of MRI and MRA using a 1.5 T magnet to detect articular cartilage lesions is limited. Neither MRI nor MRA demonstrates the intraarticular surface as accurately as direct visualization with the arthroscopy. This may be improved with the use of 3 T MRI. This study demonstrates that MRI and MRA with a 1.5 T magnet, as used in community practice, have limited ability to detect cartilage lesions of the elbow.

  3. Correlation between polarization sensitive optical coherence tomography and SHG microscopy in articular cartilage

    NASA Astrophysics Data System (ADS)

    Zhou, Xin; Ju, Myeong Jin; Huang, Lin; Tang, Shuo

    2017-02-01

    Polarization-sensitive optical coherence tomography (PS-OCT) and second harmonic generation (SHG) microscopy are two imaging modalities with different resolutions, field-of-views (FOV), and contrasts, while they both have the capability of imaging collagen fibers in biological tissues. PS-OCT can measure the tissue birefringence which is induced by highly organized fibers while SHG can image the collagen fiber organization with high resolution. Articular cartilage, with abundant structural collagen fibers, is a suitable sample to study the correlation between PS-OCT and SHG microscopy. Qualitative conjecture has been made that the phase retardation measured by PS-OCT is affected by the relationship between the collagen fiber orientation and the illumination direction. Anatomical studies show that the multilayered architecture of articular cartilage can be divided into four zones from its natural surface to the subchondral bone: the superficial zone, the middle zone, the deep zone, and the calcified zone. The different zones have different collagen fiber orientations, which can be studied by the different slopes in the cumulative phase retardation in PS-OCT. An algorithm is developed based on the quantitative analysis of PS-OCT phase retardation images to analyze the microstructural features in swine articular cartilage tissues. This algorithm utilizes the depth-dependent slope changing of phase retardation A-lines to segment structural layers. The results show good consistency with the knowledge of cartilage morphology and correlation with the SHG images measured at selected depth locations. The correlation between PS-OCT and SHG microscopy shows that PS-OCT has the potential to analyze both the macro and micro characteristics of biological tissues with abundant collagen fibers and other materials that may cause birefringence.

  4. Vulnerability of the superficial zone of immature articular cartilage to compressive injury

    PubMed Central

    Rolauffs, Bernd; Muehleman, Carol; Li, Jun; Kurz, Bodo; Kuettner, Klaus E.; Frank, Eliot; Grodzinsky, Alan J.

    2010-01-01

    Objective The zonal composition and functioning of adult articular cartilage causes depth-dependent responses to compressive injury. In immature cartilage, shear and compressive modulus, collagen and glycosaminoglycan (GAG) content also vary with depth. However, there is little understanding of depth-dependent damage caused by injury. Since injury to immature knee joints most often causes articular cartilage lesions, our objectives were to characterize the zonal dependence of biomechanical, biochemical and matrix-associated changes cause by injury. Methods Superficial and deeper zones disks from bovine calves were biomechanically characterized, injured (50% compression, 100%/sec) and re-characterized. Tissue compaction upon injury, GAG-density, GAG loss and biosynthesis were measured. Collagen-fiber-orientation and matrix damage was assessed using histology, Diffraction-Enhanced-X-Ray-Imaging, and texture analysis. Results Injured superficial disks showed surface disruption, compaction by 20.3±4.3%, and immediate biomechanical impairment: dynamic stiffness decreased to 7.1±3.3% of its initial value and equilibrium modulus was below detection. Tissue areas apparently intact by histology showed clear textural alterations. Injured deeper zones disks showed collagen crimping but remained undamaged and biomechanically intact. Superficial zone disks did not lose GAG immediately after injury but lost 17.8±1.4% by 48h; deeper zones disks lost only 2.8±0.3% GAG. Biomechanical impairment was primarily associated with structural damage. Conclusion The soft superficial zone of immature cartilage is vulnerable to compressive injury causing superficial matrix disruption, extensive compaction, and textural alteration, and resulting in immediate loss of biomechanical function. In conjunction with delayed superficial GAG loss, these changes may predispose the articular surface to further softening, damage, and increased risk of developing secondary OA. PMID:20556809

  5. Estimation of articular cartilage properties using multivariate analysis of optical coherence tomography signal.

    PubMed

    Puhakka, P H; Te Moller, N C R; Afara, I O; Mäkelä, J T A; Tiitu, V; Korhonen, R K; Brommer, H; Virén, T; Jurvelin, J S; Töyräs, J

    2015-12-01

    The aim was to investigate the applicability of multivariate analysis of optical coherence tomography (OCT) information for determining structural integrity, composition and mechanical properties of articular cartilage. Equine osteochondral samples (N = 65) were imaged with OCT, and their total attenuation and backscattering coefficients (μt and μb) were measured. Subsequently, the Mankin score, optical density (OD) describing the fixed charge density, light absorbance in amide I region (Aamide), collagen orientation, permeability, fibril network modulus (Ef) and non-fibrillar matrix modulus (Em) of the samples were determined. Partial least squares (PLS) regression model was calculated to predict tissue properties from the OCT signals of the samples. Significant correlations between the measured and predicted mean collagen orientation (R(2) = 0.75, P < 0.0001), permeability (R(2) = 0.74, P < 0.0001), mean OD (R(2) = 0.73, P < 0.0001), Mankin scores (R(2) = 0.70, P < 0.0001), Em (R(2) = 0.50, P < 0.0001), Ef (R(2) = 0.42, P < 0.0001), and Aamide (R(2) = 0.43, P < 0.0001) were obtained. Significant correlation was also found between μb and Ef (ρ = 0.280, P = 0.03), but not between μt and any of the determined properties of articular cartilage (P > 0.05). Multivariate analysis of OCT signal provided good estimates for tissue structure, composition and mechanical properties. This technique may significantly enhance OCT evaluation of articular cartilage integrity, and could be applied, for example, in delineation of degenerated areas around cartilage injuries during arthroscopic repair surgery. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  6. Effects of resveratrol on collagen type II protein in the superficial and middle zone chondrocytes of porcine articular cartilage.

    PubMed

    Maepa, Makwese; Razwinani, Mapula; Motaung, Shirley

    2016-02-03

    Resveratrol (RSV) was first isolated in 1940 from the roots of white hellebore (Veratrum grandiflorum (Maxim. ex Miq) O. Loes) and in 1963 from the roots of Japanese knotweed (Polygonum cuspidatum Siebold & Zucc.). These species have been used traditionally to treat arthritis, gout or inflammation. RSV (3,5,4-trihydroxystilbene) is a polyphenolic phytoalexin compound found in various plants, such as grape vines, berries, peanuts, seeds and roots; the highest concentration is in the skin of red grapes. This component of red wine has potent anti-inflammatory properties and may reduce the side effects of non-steroidal anti-inflammatory drugs that are currently used for pain amelioration in osteoarthritis (OA). In early degeneration of articular cartilage, which may lead to OA there is a loss of the tensile properties, indicative of damage to the fibrillar network. Damage to this fibrillar meshwork, made up of primarily collagen type II (90-95%), may be a critical event in the pathology of many arthritides, due in part to the very slow rate of collagen turnover within the cartilage. Collagen type II is the pre-dominant protein of the cartilage middle zone matrix mainly responsible for tensile strength of articular cartilage. The aim of the study was to investigate the effects of RSV on the expression of collagen type II from the superficial and middle zone chondrocytes of porcine articular cartilage. Porcine articular chondrocytes were isolated from the superficial and middle zone of articular cartilage, cultured as monolayers in serum-free chemically defined medium for four days. Effects of RSV on porcine articular chondrocytes were studied by assessing expression of collagen type II mRNA by RT-PCR and protein levels of collagen type II by ELISA; as well as localisation of collagen type II on cartilage tissue sections using immunohistochemistry. RSV significantly stimulated the expression of collagen type II at the mRNA and protein levels in the superficial and middle

  7. Biochemical magnetic resonance imaging of knee articular cartilage: T1rho and T2 mapping as cartilage degeneration biomarkers.

    PubMed

    Le, Jenna; Peng, Qi; Sperling, Karen

    2016-11-01

    Osteoarthritis (OA) is a disease whose hallmark is the degeneration of articular cartilage. There is a worsening epidemic of OA in the United States today, with considerable economic costs. In order to develop more effective treatments for OA, noninvasive biomarkers that permit early diagnosis and treatment monitoring are necessary. T1rho and T2 mapping are two magnetic resonance imaging techniques that have shown great promise as noninvasive biomarkers of cartilage degeneration. Each of the two techniques is endowed with advantages and disadvantages: T1rho can discern earlier biochemical changes of OA than T2 mapping, while T2 mapping is more widely available and can be incorporated into existing imaging protocols in a more time-efficient manner than T1rho. Both techniques have been applied in numerous instances to study how cartilage is affected by OA risk factors, such as age and exercise. Additionally, both techniques have been repeatedly applied to the study of posttraumatic OA in patients with torn anterior cruciate ligaments. © 2016 New York Academy of Sciences.

  8. 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).

  9. 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.

  10. Strain-Dependent Oxidant Release in Articular Cartilage Originates from Mitochondria

    PubMed Central

    J, Brouillette M; S, Ramakrishnan P; M, Wagner V; E, Sauter E; J, Journot B; O, McKinley T; A, Martin J

    2013-01-01

    Mechanical loading is essential for articular cartilage homeostasis and plays a central role in the cartilage pathology, yet the mechanotransduction processes that underlie these effects remain unclear. Previously we showed that lethal amounts of reactive oxygen species (ROS) were liberated from the mitochondria in response to mechanical insult, and that chondrocyte deformation may be a source of ROS. To this end, we hypothesized that mechanically-induced mitochondrial ROS is related to the magnitude of cartilage deformation. To test this, we measured axial tissue strains in cartilage explants subjected to semi-confined compressive stresses of 0, 0.05, 0.1, 0.25, 0.5, or 1.0 MPa. The presence of ROS was then determined by confocal imaging with dihydroethidium (DHE), an oxidant sensitive fluorescent probe. Our results indicated that ROS levels increased linearly relative to the magnitude of axial strains (r2 = 0.83, p < 0.05), and significant cell death was observed at strains > 40%. By contrast, hydrostatic stress, which causes minimal tissue strain, had no significant effect. Cell permeable superoxide dismutase mimetic Mn(III)tetrakis (1-methyl-4-pyridyl) porphyrin pentachloride (MnTMPyP) significantly decreased ROS levels at 0.5 and 0.25 MPa. Electron transport chain inhibitor, rotenone, and cytoskeletal inhibitor, cytochalasin B, significantly decreased ROS levels at 0.25 MPa. Our findings strongly suggest that ROS and mitochondrial oxidants contribute to cartilage mechanobiology. PMID:23896937

  11. 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

  12. 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.

  13. [The effect of intra-articular levobupivacaine on shoulder cartilage at different doses-experimental study].

    PubMed

    Özcan, Mustafa Soner; Kalem, Mahmut; Özçelik, Menekşe; Şahin, Ercan; Çakar, Sanem; Hayırlı, Nazlı; Evirgen, Oya; Ökten, Feyhan

    In this study it was aimed to examine the histological and morphometric effects on cartilage structure of intra-articular application of levobupivacaine to the shoulder joint. In twenty New Zealand adult male rabbits, 35 shoulders were used for the study and prepared in 5 groups of 7. These groups were defined as Groups L1, L2, L3 and L4 which were right shoulders administered with 0.25% and 0.5% levobupivacaine, Group C which were left shoulders as the control group and Groups S1 and S2 which were left shoulders administered with 0.9% saline. On the 2nd and 15th days the animals were killed, the glenohumeral joints were evaluated macroscopically then cartilage samples were taken. These samples were evaluated with Mankin score, and histomorphometrically by measuring the thickness of the cartilage between the superficial cartilage layer and the tidemark and the thickness of calcified cartilage between the tidemark and the subchondral bone. Macroscopically, on the 15th day the joint fluid was seen to have reduced in all the groups. After microscopic evaluation, the highest Mankin score (mean: 3.14±2.1/14) was in the L4 group (15th day 0.5% levobupivacaine) and was found to be statistically significant (p<0.05). No statistically significant difference was determined between the other groups. Histologically, as the highest Mankin score was in the L4 group, this indicates that in a single intra-articular injection of levobupivacaine a low concentration should be selected. Level 5, animal study. Copyright © 2016 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  14. 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

  15. 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

  16. Increased Hydraulic Conductance of Human Articular Cartilage and Subchondral Bone Plate with Progression of Osteoarthritis

    PubMed Central

    Hwang, Jennifer; Bae, Won C.; Shieu, Wendy; Lewis, Chad W.; Bugbee, William D.; Sah, Robert L.

    2008-01-01

    Objective Osteoarthritis (OA) is characterized by progressive degeneration of articular cartilage and remodeling of the subchondral bone plate (ScBP), comprised of calcified cartilage (CC) and underlying subchondral bone (ScB). CC remodeling due to upward invasion by vascular canals or to CC erosion may contribute to biomechanical alteration of the osteochondral (OC) tissue and its ScBP component. The study hypothesis was that hydraulic conductance of OC tissue and ScBP increases with structural changes indicative of increasing stages of OA. Methods OC cores were harvested from knees of cadaveric tissue donors and from discarded fragments of OA knee surgery patients. Tissue donor cores were macroscopically normal, and OA cores had partial- or full-thickness erosion to bone. Cores were perfusion-tested to determine the hydraulic conductance, or ease of fluid flow, in their native state and after enzymatic removal of cartilage. Adjacent portions were analyzed by 3-D histology for CC, ScB, and ScBP thickness and vascular canal density. Results The hydraulic conductances of native OC tissue and ScBP were higher (2700- and 3-fold) in fully eroded samples than normal samples. The CC layer was thicker (1.5-fold) in partially eroded samples than normal samples, but thinner and incomplete in fully eroded samples. ScBP vascularity was altered with increasing stages of OA. Conclusion During joint loading, increased hydraulic conductance of the OC tissue and ScBP could have deleterious biomechanical consequences for cartilage. Increased fluid exudation from overlying and opposing cartilage, increased fluid depressurization, and increased cartilage tissue strains could lead to chondrocyte death and cartilage damage. PMID:19035476

  17. The effect of recombinant human fibroblast growth factor-18 on articular cartilage following single impact load.

    PubMed

    Barr, Lynne; Getgood, Alan; Guehring, Hans; Rushton, Neil; Henson, Frances M D

    2014-07-01

    The aim of this in vitro study was to ascertain the effect of recombinant human Fibroblast Growth Factor-18 (rhFGF18) on the repair response of mechanically damaged articular cartilage. Articular cartilage discs were harvested from healthy mature horses (n = 4) and subjected to single impact load (SIL). The impacted explants, together with unimpacted controls were cultured in modified DMEM ± 200 ng/ml rhFGF18 for up to 30 days. Glycosaminoglycan (GAG) release into the media was measured using the dimethylmethylene blue (DMMB) assay. Aggrecan neopepitope CS846, collagen type II synthesis (CPII) and cleavage (C2C) were measured by ELISA. Histological analysis and TUNEL staining were used to assess repair cell number and cell death. Impacted explants treated with rhFGF18 showed significantly more GAG and CS846 release into the media (p < 0.05), there was also a significant decrease in C2C levels at Day 20. Loaded sections treated with rhFGF18 had more repair cells and significantly less cell death (p < 0.001) at Day 30 in culture. In an in vitro damage/repair model, rhFGF18 increases the proteoglycan synthesis, the repair cell number and prevents apoptosis at Day 30. This suggests that rhFGF18 may be a good candidate for enhancement of cartilage repair following mechanical damage. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  18. Assessment of common hyperelastic constitutive equations for describing normal and osteoarthritic articular cartilage.

    PubMed

    Brown, C P; Nguyen, T C; Moody, H R; Crawford, R W; Oloyede, A

    2009-08-01

    With the aim of providing information for modelling joint and limb systems, widely available constitutive hyperelastic laws are evaluated in this paper for their ability to predict the mechanical responses of normal and osteoarthritic articular cartilage. Load-displacement data from mechanical indentation were obtained for normal and osteoarthritic cartilage at 0.1 s(-1) and 0.025 s(-1) and converted to the stress-stretch ratio. The data were then fitted to the Arruda-Boyce, Mooney-Rivlin, neo-Hookean, Ogden, polynomial, and Yeoh hyperelastic laws in the MATLAB environment. Although each of the hyperelastic laws performed satisfactorily at the higher rate of loading, their ability to fit experimental data at the lower loading rate varied considerably. For the preferred models, coefficients were provided for stiff, soft, and average tissues to represent normal and degraded tissue at high and low loading rates. The present authors recommend the use of the Mooney-Rivlin or the Yeoh models for describing both normal and degraded articular cartilage, with the Mooney-Rivlin model providing the best compromise between accuracy and required computational power.

  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. 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.

  2. 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

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

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

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

  4. Stimulation of the Superficial Zone Protein and Lubrication in the Articular Cartilage by Human Platelet-Rich Plasma

    PubMed Central

    Sakata, Ryosuke; McNary, Sean M.; Miyatake, Kazumasa; Lee, Cassandra A.; Van den Bogaerde, James M.; Marder, Richard A.; Reddi, A. Hari

    2016-01-01

    Background Platelet-rich plasma (PRP) contains high concentrations of autologous growth factors that originate from platelets. Intra-articular injections of PRP have the potential to ameliorate the symptoms of osteoarthritis in the knee. Superficial zone protein (SZP) is a boundary lubricant in articular cartilage and plays an important role in reducing friction and wear and therefore is critical in cartilage homeostasis. Purpose To determine if PRP influences the production of SZP from human joint-derived cells and to evaluate the lubricating properties of PRP on normal bovine articular cartilage. Study Design Controlled laboratory study. Methods Cells were isolated from articular cartilage, synovium, and the anterior cruciate ligament (ACL) from 12 patients undergoing ACL reconstruction. The concentrations of SZP in PRP and culture media were measured by enzyme-linked immunosorbent assay. Cellular proliferation was quantified by determination of cell numbers. The lubrication properties of PRP from healthy volunteers on bovine articular cartilage were investigated using a pin-on-disk tribometer. Results In general, PRP stimulated proliferation in cells derived from articular cartilage, synovium, and ACL. It also significantly enhanced SZP secretion from synovium- and cartilage-derived cells. An unexpected finding was the presence of SZP in PRP (2.89 ± 1.23 µg/mL before activation and 3.02 ± 1.32 µg/mL after activation). In addition, under boundary mode conditions consisting of high loads and low sliding speeds, nonactivated and thrombin-activated PRP decreased the friction coefficient (μ = 0.012 and μ = 0.015, respectively) compared with saline (μ = 0.047, P < 0.004) and high molecular weight hyaluronan (μ = 0.080, P < 0.006). The friction coefficient of the cartilage with PRP was on par with that of synovial fluid. Conclusion PRP significantly stimulates cell proliferation and SZP secretion by articular cartilage and synovium of the human knee joint

  5. Immunohistochemical localization of fibroblast growth factor-2 in normal and brachymorphic mouse tibial growth plate and articular cartilage.

    PubMed

    Wezeman, F H; Bollnow, M R

    1997-06-01

    Epiphyses of the proximal tibiae of 7-week-old normal and homozygous recessive brachymorphic mice (bm/bm) were immunostained using a monoclonal antibody to basic fibroblast growth factor to determine its expression in growth plate cartilage, osteoblasts on the surfaces of the primary spongiosa and articular cartilage. In the normal growth plate the immunoreactive factor was present in chondrocytes of the proliferating and upper hypertrophic zones but absent from lower hypertrophic chondrocytes. Immunostaining was present only in the territorial extracellular matrix immediately adjacent to the chondrocytes of the proliferating and upper hypertrophic zones. Osteoblasts of the primary spongiosa stained heavily in normal mice. Strong staining was observed in intermediate zone articular chondrocytes. Cells in the superficial layer of articular cartilage were unstained. The extracellular matrix of the articular cartilage was completely free of immunostaining. In contrast, the reduced size of bm/bm growth plates was accompanied by significantly reduced staining intensity in proliferating and upper hypertrophic chondrocytes, and staining was absent from the territorial extracellular matrix of all zones of the bm/bm growth plate. Osteoblasts of the primary spongiosa of bm/bm mice stained less than those of normal mice. Articular cartilage chondrocytes in the intermediate zone stained with less intensity in bm/bm mice, and the cells of the superficial layer were unstained. The extracellular matrix of bm/bm articular cartilage was completely free of staining. Brachymorphic epiphyseal growth plate and articular chondrocytes, and osteoblasts in the primary spongiosa, express reduced amounts of immunoreactive fibroblast growth factor-2. This phenotypical characteristic may be associated with abnormal endochondral ossification and development of bone in brachymorphic mice.

  6. 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

  7. 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

  8. T2* mapping and delayed gadolinium-enhanced magnetic resonance imaging in cartilage (dGEMRIC) of humeral articular cartilage--a histologically controlled study.

    PubMed

    Bittersohl, Bernd; Kircher, Jörn; Miese, Falk R; Dekkers, Christin; Habermeyer, Peter; Fröbel, Julia; Antoch, Gerald; Krauspe, Rüdiger; Zilkens, Christoph

    2015-10-01

    Cartilage biochemical imaging modalities that include the magnetic resonance imaging (MRI) techniques of T2* mapping (sensitive to water content and collagen fiber network) and delayed gadolinium-enhanced MRI of cartilage (dGEMRIC, sensitive to the glycosaminoglycan content) can be effective instruments for early diagnosis and reliable follow-up of cartilage damage. The purpose of this study was to provide T2* mapping and dGEMRIC values in various histologic grades of cartilage degeneration in humeral articular cartilage. A histologically controlled in vitro study was conducted that included human humeral head cartilage specimens with various histologic grades of cartilage degeneration. High-resolution, 3-dimensional (3D) T2* mapping and dGEMRIC were performed that enabled the correlation of MRI and histology data. Cartilage degeneration was graded according to the Mankin score, which evaluates surface morphology, cellularity, toluidine blue staining, and tidemark integrity. SPSS software was used for statistical analyses. Both MRI mapping values decreased significantly (P < .001) with increasing cartilage degeneration. Spearman rank analysis revealed a significant correlation (correlation coefficients ranging from -0.315 to 0.784; P < .001) between the various histologic parameters and the T2* and T1Gd mapping values. This study demonstrates the feasibility of 3D T2* and dGEMRIC to identify various histologic grades of cartilage damage of humeral articular cartilage. With regard to the advantages of these mapping techniques with high image resolution and the ability to accomplish a 3D biochemically sensitive imaging, we consider that these imaging techniques can make a positive contribution to the currently evolving science and practice of cartilage biochemical imaging. Copyright © 2015 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

  9. Glenohumeral articular cartilage lesions: prospective comparison of non-contrast magnetic resonance imaging and findings at arthroscopy.

    PubMed

    Spencer, Brian A; Dolinskas, Carol A; Seymour, Peter A; Thomas, Stephen J; Abboud, Joseph A

    2013-09-01

    The purpose of this study was to assess the diagnostic sensitivity, specificity, accuracy, negative predictive value (NPV), positive predictive value (PPV), and test-retest reliability of magnetic resonance imaging (MRI) for detecting cartilage abnormalities of the glenohumeral joint in comparison with the gold standard of diagnostic arthroscopy. Forty-four patients with a preoperative non-contrast MRI study of their affected shoulder underwent arthroscopy by one surgeon for rotator cuff tendinopathy from 2009 to 2010. Articular cartilage defects were prospectively recorded and graded according to the International Cartilage Repair Society classification system at the time of arthroscopy. One year after surgery, the preoperative MRI were reviewed by a board-certified radiologist and the treating surgeon for articular cartilage defects of both the humeral head and the glenoid. Sensitivity, specificity, accuracy, and test-retest reliability were calculated. At arthroscopy, 43% of the shoulders were found to have articular cartilage defects. When the readers' findings were combined, the sensitivity of detecting humeral lesions on MRI was 32%; specificity, 80%; accuracy, 63%; PPV, 57%; and NPV, 66%. The sensitivity of detecting glenoid lesions was 31%; specificity, 86%; accuracy, 76%; PPV, 33%; and NPV, 85%. This study finds that the overall accuracy of MRI in detecting articular cartilage damage in patients with the clinical diagnosis of subacromial pathology is moderate. Level II, development of diagnostic criteria based on consecutive patients with universally applied reference "gold" standard. Copyright © 2013 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

  10. Loss of extracellular matrix from articular cartilage is mediated by the synovium and ligament after anterior cruciate ligament injury.

    PubMed

    Haslauer, C M; Elsaid, K A; Fleming, B C; Proffen, B L; Johnson, V M; Murray, M M

    2013-12-01

    Post-traumatic osteoarthritis (PTOA) occurs after anterior cruciate ligament (ACL) injury. PTOA may be initiated by early expression of proteolytic enzymes capable of causing degradation of the articular cartilage at time of injury. This study investigated the production of three of these key proteases in multiple joint tissues after ACL injury and subsequent markers of cartilage turnover. ACL transection was performed in adolescent minipigs. Collagenase (MMP-1 and MMP-13) and aggrecanase (ADAMTS-4) gene expression changes were quantified in the articular cartilage, synovium, injured ligament, and the provisional scaffold at days 1, 5, 9, and 14 post-injury. Markers of collagen degradation (C2C), synthesis (CPII) and aggrecan synthesis (CS 846) were quantified in the serum and synovial fluid. Histologic assessment of the cartilage integrity (OARSI scoring) was also performed. MMP-1 gene expression was upregulated in the articular cartilage, synovium and ligament after ACL injury. MMP-13 expression was suppressed in the articular cartilage, but upregulated 100-fold in the synovium and ligament. ADAMTS-4 was upregulated in the synovium and ligament but not in the articular cartilage. The concentration of collagen degradation fragments (C2C) in the synovial joint fluid nearly doubled in the first five days after injury. We conclude that upregulation of genes coding for proteins capable of degrading cartilage ECM is seen within the first few days after ACL injury, and this response is seen not only in chondrocytes, but also in cells in the synovium, ligament and provisional scaffold. Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  11. 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

  12. 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.

  13. The impact of forced joint exercise on lubricin biosynthesis from articular cartilage following ACL transection and intra-articular lubricin's effect in exercised joints following ACL transection.

    PubMed

    Elsaid, K A; Zhang, L; Waller, K; Tofte, J; Teeple, E; Fleming, B C; Jay, G D

    2012-08-01

    To evaluate the impact of forced joint exercise following acute knee injury on lubricin metabolism and its relationship to cartilage degeneration and to assess chondroprotection of a single-dose purified human lubricin injection in exercised injured joints. Anterior cruciate ligament transection (ACLT) was performed in rats with six experimental groups; 3-week post-ACLT, 3-week post-ACLT + exercise, 5-week post-ACLT, 5-week post-ACLT + exercise, and 5-week post-ACLT + exercise treated with intra-articular phosphate buffered saline (PBS) or lubricin. Joint exercise was achieved using a rotating cylinder at a speed of 6 rpm for 30 min daily, 5 days a week starting 1 week following surgery. Cartilage lubricin expression in injured joints was determined. Histological analyses included Safranin O/Fast Green, activated caspase-3, and lubricin mRNA in-situ hybridization. Assessment of cartilage damage was performed by osteoarthritis research society international (OARSI) modified Mankin scoring and urinary CTXII (uCTXII) levels. At 3 weeks, lubricin expression in exercised ACLT joints was significantly (P < 0.001) lower compared to ACLT joints. The OARSI scores were significantly (P < 0.001) higher in the ACLT + exercise animals compared to ACLT animals at 5 weeks. Compared to 3-week ACLT, 3-week ACLT + exercise cartilage showed increased caspase-3 staining. Compared to ACLT + exercise and PBS-treated ACLT + exercise, lubricin intra-articular treatment resulted in a significant increase (P < 0.001) in cartilage lubricin gene expression and a reduction (P < 0.05) in uCTXII levels. Joint exercise resulted in decreased lubricin cartilage expression, increased cartilage degeneration and reduced superficial zone chondrocyte viability in the ACLT joint. Intra-articular lubricin administration ameliorated cartilage damage due to exercise and preserved superficial zone chondrocytes' viability. Copyright © 2012 Osteoarthritis Research Society International. Published by Elsevier

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

    PubMed Central

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

    2014-01-01

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

  15. 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. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

    PubMed

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

    2014-10-01

    High density mineralised protrusions (HDMP) from the tidemark mineralising front into hyaline articular cartilage (HAC) were first described in Thoroughbred racehorse fetlock joints and later in Icelandic horse hock joints. We now report them in human material. Whole femoral heads removed at operation for joint replacement or from dissection room cadavers were imaged using magnetic resonance imaging (MRI) dual echo steady state at 0.23 mm resolution, then 26-μm resolution high contrast X-ray microtomography, sectioned and embedded in polymethylmethacrylate, blocks cut and polished and re-imaged with 6-μm resolution X-ray microtomography. Tissue mineralisation density was imaged using backscattered electron SEM (BSE SEM) at 20 kV with uncoated samples. HAC histology was studied by BSE SEM after staining block faces with ammonium triiodide solution. HDMP arise via the extrusion of an unknown mineralisable matrix into clefts in HAC, a process of acellular dystrophic calcification. Their formation may be an extension of a crack self-healing mechanism found in bone and articular calcified cartilage. Mineral concentration exceeds that of articular calcified cartilage and is not uniform. It is probable that they have not been reported previously because they are removed by decalcification with standard protocols. Mineral phase morphology frequently shows the agglomeration of many fine particles into larger concretions. HDMP are surrounded by HAC, are brittle, and show fault lines within them. Dense fragments found within damaged HAC could make a significant contribution to joint destruction. At least larger HDMP can be detected with the best MRI imaging ex vivo. © 2014 Anatomical Society.

  17. Using Costal Chondrocytes to Engineer Articular Cartilage with Applications of Passive Axial Compression and Bioactive Stimuli.

    PubMed

    Huwe, Le W; Sullan, Gurdeep K; Hu, Jerry C; Athanasiou, Kyriacos A

    2017-08-14

    Generating neocartilage with suitable mechanical integrity from a cell source that can circumvent chondrocyte scarcity is indispensable for articular cartilage regeneration strategies. Costal chondrocytes of the rib eliminate donor site morbidity in the articular joint, but it remains unclear how neocartilage formed from these cells responds to mechanical loading, especially if the intent is to use it in a load-bearing joint. In a series of three experiments, this study sought to determine efficacious parameters of passive axial compressive stimulation that would enable costal chondrocytes to synthesize mechanically robust cartilage. Experiment 1 determined a suitable time window for stimulation by its application during either the matrix synthesis phase, the maturation phase, or during both phases of the self-assembling process. The results showed that compressive stimulation at either time was effective in increasing instantaneous moduli by 92% and 87% in the synthesis and maturation phases, respectively. Compressive stimulation during both phases did not further improve properties beyond a one-time stimulation. The magnitude of passive axial compression was examined in Experiment 2 by applying 0, 3.3, 5.0, or 6.7 kPa stresses to the neocartilage. Unlike 6.7 kPa, both 3.3 and 5.0 kPa significantly increased neocartilage compressive properties by 42% and 48% over untreated controls, respectively. Experiment 3 examined how the passive axial compression regimen developed from the previous phases interacted with a bioactive regimen (transforming growth factor [TGF]-β1, chondroitinase ABC, and lysyl oxidase-like 2). Passive axial compression significantly improved the relaxation modulus compared with bioactive treatment alone. Furthermore, a combined treatment of compressive and bioactive stimulation improved the tensile properties of neocartilage 2.6-fold compared with untreated control. The ability to create robust articular cartilage from passaged costal

  18. Direct gene transfer into rat articular cartilage by in vivo electroporation.

    PubMed

    Grossin, Laurent; Cournil-Henrionnet, Christel; Mir, Lluis M; Liagre, Bertrand; Dumas, Dominique; Etienne, Stéphanie; Guingamp, Corinne; Netter, Patrick; Gillet, Pierre

    2003-05-01

    To establish a system for efficient direct in vivo gene targeting into rat joint, we have evaluated a strategy of gene transfer by means of the delivery of external electric pulses (EP) to the knee after intra-articular injection of a reporter gene (GFP). Rats were killed at various times after the electro gene-therapy to analyze GFP gene expression by immunohistochemistry. GFP staining was detected in the superficial, middle, and deep zones of the patellar cartilage at days 2 and 9, and thereafter only in the deep zone (months 1 and 2). The average percentage of GFP-positive cells was estimated at 30% both one and 2 months after the gene transfer. Moreover, no pathologic change caused by the EP was detected in the cartilage. The level and stability of the long-term GFP expression found in this study demonstrate the feasibility of a treatment of joint disorders (inflammatory or degenerative, focal or diffuse) using electric gene transfer.

  19. 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.

  20. Elastoviscous Transitions of Articular Cartilage Reveal a Mechanism of Synergy between Lubricin and Hyaluronic Acid

    PubMed Central

    Bonnevie, Edward D.; Galesso, Devis; Secchieri, Cynthia; Cohen, Itai; Bonassar, Lawrence J.

    2015-01-01

    When lubricated by synovial fluid, articular cartilage provides some of the lowest friction coefficients found in nature. While it is known that macromolecular constituents of synovial fluid provide it with its lubricating ability, it is not fully understood how two of the main molecules, lubricin and hyaluronic acid, lubricate and interact with one another. Here, we develop a novel framework for cartilage lubrication based on the elastoviscous transition to show that lubricin and hyaluronic acid lubricate by distinct mechanisms. Such analysis revealed nonspecific interactions between these molecules in which lubricin acts to concentrate hyaluronic acid near the tissue surface and promotes a transition to a low friction regime consistent with the theory of viscous boundary lubrication. Understanding the mechanics of synovial fluid not only provides insight into the progression of diseases such as arthritis, but also may be applicable to the development of new biomimetic lubricants. PMID:26599797

  1. 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

  2. An Experimental and Finite Element Protocol to Investigate the Transport of Neutral and Charged Solutes across Articular Cartilage.

    PubMed

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

    2017-04-23

    Osteoarthritis (OA) is a debilitating disease that is associated with degeneration of articular cartilage and subchondral bone. Degeneration of articular cartilage impairs its load-bearing function substantially as it experiences tremendous chemical degradation, i.e. proteoglycan loss and collagen fibril disruption. One promising way to investigate chemical damage mechanisms during OA is to expose the cartilage specimens to an external solute and monitor the diffusion of the molecules. The degree of cartilage damage (i.e. concentration and configuration of essential macromolecules) is associated with collisional energy loss of external solutes while moving across articular cartilage creates different diffusion characteristics compared to healthy cartilage. In this study, we introduce a protocol, which consists of several steps and is based on previously developed experimental micro-Computed Tomography (micro-CT) and finite element modeling. The transport of charged and uncharged iodinated molecules is first recorded using micro-CT, which is followed by applying biphasic-solute and multiphasic finite element models to obtain diffusion coefficients and fixed charge densities across cartilage zones.

  3. 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.

  4. 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

  5. Study on nano-structured hydroxyapatite/zirconia stabilized yttria on healing of articular cartilage defect in rabbit.

    PubMed

    Sotoudeh, Amir; Jahanshahi, Amirali; Takhtfooladi, Mohammad Ashrafzadeh; Bazazan, Ali; Ganjali, Amin; Harati, Maryam Pourramezani

    2013-05-01

    Articular Cartilage has limited potential for self-repair and tissue engineering approaches attempt to repair articular cartilage by scaffolds. We hypothesized that the combined hydroxyapatite and zirconia stabilized yttria would enhance the quality of cartilage healing. In ten New Zealand white rabbits bilateral full-thickness osteochondral defect, 4 mm in diameter and 3 mm depth, was created on the articular cartilage of the patellar groove of the distal femur. In group I the scaffold was implanted into the right stifle and the same defect was created in the left stifle without any transplant (group II). Specimens were harvested at 12 weeks after implantation, examined histologically for morphologic features, and stained immunohistochemically for type-II collagen. In group I the defect was filled with a white translucent cartilage tissue In contrast, the defects in the group II remained almost empty. In the group I, the defects were mostly filled with hyaline-like cartilage evidenced but defects in group II were filled with fibrous tissue with surface irregularities. Positive immunohistochemical staining of type-II collagen was observed in group I and it was absent in the control group. The hydroxyapatite/yttria stabilized zirconia scaffold would be an effective scaffold for cartilage tissue engineering.

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. Chronic changes in the articular cartilage and meniscus following traumatic impact to the lapine knee.

    PubMed

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

    2015-01-21

    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 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 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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. 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.

  13. 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

  14. Microfracture technique versus carbon fibre rod implantation for treatment of knee articular cartilage lesions.

    PubMed

    Dasar, U; Gursoy, S; Akkaya, M; Algin, O; Isik, C; Bozkurt, M

    2016-08-01

    To compare the microfracture technique with carbon fibre rod implantation for treatment of knee articular cartilage lesions. 10 m