Showing papers on "Cartilage published in 1995"
TL;DR: It is demonstrated that mesenchymal precursor cells from marrow that are expanded in culture can serve as long-lasting precursors for mesenchcyal cells in bone, cartilage, and lung and suggest that cells may be particularly attractive targets for gene therapy ex vivo.
Abstract: Cells from transgenic mice expressing a human mini-gene for collagen I were used as markers to follow the fate of mesenchymal precursor cells from marrow that were partially enriched by adherence to plastic, expanded in culture, and then injected into irradiated mice. Sensitive PCR assays for the marker collagen I gene indicated that few of the donor cells were present in the recipient mice after 1 week, but 1-5 months later, the donor cells accounted for 1.5-12% of the cells in bone, cartilage, and lung in addition to marrow and spleen. A PCR in situ assay on lung indicated that the donor cells diffusely populated the parenchyma, and reverse transcription-PCR assays indicated that the marker collagen I gene was expressed in a tissue-specific manner. The results, therefore, demonstrated that mesenchymal precursor cells from marrow that are expanded in culture can serve as long-lasting precursors for mesenchymal cells in bone, cartilage, and lung. They suggest that cells may be particularly attractive targets for gene therapy ex vivo.
953 citations
TL;DR: The hypothesis that deformation of chondrocytes or a change in their volume may occur during in vivo joint loading and may have a role in the mechanical signal transduction pathway of articular cartilage is supported.
494 citations
TL;DR: The special nature of the chondrocyte is stressed in connection with its cell involvement in osteoarthritis, the most widespread disease of diarthrodial joints.
Abstract: Chondrocytes are specialised cells which produce and maintain the extracellular matrix of cartilage, a tissue that is resilient and pliant. In vivo, it has to withstand very high compressive loads, and that is explicable in terms of the physico-chemical properties of cartilage-specific macromolecules and with the movement of water and ions within the matrix. The functions of the cartilage-specific collagens, aggrecan (a hydrophilic proteoglycan) and hyaluronan are discussed within this context. The structures of cartilage collagens and proteoglycans and their genes are known and a number of informative mutations have been identified. In particular, collagen fibrillogenesis is a complex process which can be altered by mutations whose effects fit what is known about collagen molecular structural functions. In other instances, mutations have indicated new functions for particular molecular domains. As cartilage provides the template for the developing skeleton, mutations in genes for cartilage-specific proteins often produce developmental abnormalities. The search for mutations amongst such genes in heritable disorders is being actively pursued by many groups, although mutation and phenotype are not always well correlated, probably because of compensatory mechanisms. The special nature of the chondrocyte is stressed in connection with its cell involvement in osteoarthritis, the most widespread disease of diarthrodial joints.
440 citations
TL;DR: It is suggested that NO is produced primarily by CD14+ synoviocytes, chondrocytes, and endothelial cells in inflammatory joints of arthritides, and can be upregulated by cytokines present in inflamed joints.
Abstract: In this study, we have identified the source of nitric oxide (NO) produced in the human inflammatory joints by analyzing expression of inducible NO synthase. In ex vivo organ cultures, both inflammatory synovium and cartilage from patients with rheumatoid arthritis produced NO. The NO production was suppressed by NG-monomethyl-L-arginine, an inhibitor of NO synthase. The amount of NO produced by the synovium correlated with the proportion of CD14+ cells in the corresponding tissue (r = 0.8, P < 0.05). Immunohistochemical analysis as well as in situ hybridization showed that inducible NO synthase was predominantly expressed in synovial lining cells, endothelial cells, chondrocytes, and to a lesser extent, in infiltrating mononuclear cells and synovial fibroblasts. The synovial lining cells and the infiltrating cells expressing inducible NO synthase were identified where CD14+ cells were located. Together with morphological features, this suggests that they are type A synoviocytes. NO production from freshly isolated synoviocytes and chondrocytes was up-regulated by in vitro stimulation with a combination of IL-TNF-beta, TNF-alpha, and LPS. In summary, the present results suggest that NO is produced primarily by CD14+ synoviocytes, chondrocytes, and endothelial cells in inflammatory joints of arthritides. NO production can be upregulated by cytokines present in inflamed joints. The increased NO production may thus contribute to the pathological features in inflammatory arthritides.
412 citations
Patent•
06 Jun 1995TL;DR: In this paper, a method for the repair of articular cartilage defects in a mammal is described, where denuded chondrogenic cells are proliferated ex vivo as monolayer cultures in order to expand the pool of available chondrogensic cells.
Abstract: Provided are methods and compositions for the repair of articular cartilage defects in a mammal. Denuded chondrogenic cells are proliferated ex vivo as monolayer cultures in order to expand the pool of available chondrogenic cells. During proliferation the chondrogenic cells stop secreting the extracellular matrix components, type II collagen and sulfated proteoglycans. The proliferated cells then are seeded into a pre-shaped well having a cell contacting, cell abhesive surface. The cells cultured in the well redifferentiate and begin to secrete cartilage-specific extracellular matrix again. Accordingly, essentially unlimited amounts of synthetic cartilage may be prepared from small samples of biopsy tissue. Also provided are methods for surgically repairing articular cartilage defects in mammals using the synthetic cartilage prepared in accordance with the invention.
410 citations
TL;DR: The suppression of PG synthesis in both ZIA and AIA in mice is due to the combined local action of IL-1 (alpha + beta), and neither IL-6 nor TNF is involved.
Abstract: OBJECTIVE: To determine the involvement of interleukin-1 (IL-1), tumor necrosis factor (TNF), and IL-6 in the cartilage pathology of murine antigen-induced arthritis (AIA) and zymosan-induced arthritis (ZIA). METHODS: Arthritis was induced by intraarticular injection of zymosan in naive mice or by subcutaneous injection of methylated bovine serum albumin in sensitized animals. Mini-osmotic pumps releasing human recombinant IL-1 receptor antagonist (IL-1ra) protein were implanted intraperitoneally 2 days before arthritis induction, and neutralizing antibodies directed against murine IL-1 alpha, IL-1 beta, TNF alpha, or IL-6 were administered 1 day before. Proteoglycan (PG) synthesis and degradation were assessed in patellar cartilage. RESULTS: Murine IL-1 alpha and IL-1 beta injected intraarticularly at doses of 0.1-100 ng suppressed chondrocyte PG synthesis. The highest dose of TNF tested (100 ng) decreased PG synthesis marginally. In contrast, the maximum dose of IL-6 (1 microgram) stimulated PG synthesis 2 days after injection. Treatment of AIA with neutralizing monoclonal antibodies against either TNF alpha or IL-6 did not reduce either the PG degradation or the suppression of its synthesis. However, treatment with anti-IL-1 (alpha + beta) polyclonal antibodies totally prevented PG suppression, although the initial breakdown of PG was unaffected. This effect was confirmed when IL-1ra was administered in high doses. Moreover, treatment of ZIA with anti-IL-1 (alpha + beta), but not with anti-TNF, resulted in normal PG synthesis, confirming the key role played by IL-1 in the inhibition of PG synthesis. Treatment of AIA with anti-IL-1 did not affect inflammation during the acute phase, but a significant reduction of ongoing inflammation was noted at day 7, and there was a marked reduction in the loss of cartilage PG. CONCLUSION: The suppression of PG synthesis in both ZIA and AIA in mice is due to the combined local action of IL-1 (alpha + beta), and neither IL-6 nor TNF is involved. Moreover, the normalization of PG synthesis brought about by blocking of IL-1 ameliorates the cartilage damage associated with AIA.
391 citations
TL;DR: This paper showed that the normal differentiation and spatial organization of growth plate chondrocytes is critially dependent on the presence of type XI collagen in cartilage extracellular matrix.
352 citations
TL;DR: Results suggest that scaffolds composed of porous D,D-L,L-polylactic acid support the growth of cartilaginous repair tissue and are compatible with both in vitro and in vivo survival of chondrogenic cells.
Abstract: Efforts to expand treatment options for articular cartilage repair have increasingly focused on the implantation of cell-polymer constructs. The purpose of this study is to determine the suitability of porous D,D-L,L-polylactic acid as a carrier for delivering repair cells obtained from rib perichondrium into full-thickness articular cartilage defects. In vitro characterization of perichondrocyte-polylactic acid composite grafts was combined with in vivo assessment of the early articular cartilage repair in a clinically relevant model. Using a fluorescent double-stain protocol to visualize live and dead cells in situ, primary cells cultured from perichondrium were found to be capable of attaching to and surviving within a porous D,D-L,L-polylactic acid matrix. These perichondrocyte-polylactic acid composite grafts were then implanted within osteochondral defects drilled into the left medial femoral condyles of 16 adult New Zealand white rabbits. Experimental animals were sacrificed 6 weeks after implantation and the repair tissue was evaluated grossly, histologically, and biochemically. Grossly, 96% (15/16) of the experimental animals demonstrated repairs consisting of a smooth, firm neocartilage which appeared similar in color and texture to the surrounding articular surface. Matrix staining for cartilaginous protein was seen surrounding chondrocyte-like cells in the cartilage regions of the repair. Cellular alignment was found to be related to scaffold architecture. These results suggest that scaffolds composed of porous D,D-L,L-polylactic acid support the growth of cartilaginous repair tissue and are compatible with both in vitro and in vivo survival of chondrogenic cells.
305 citations
TL;DR: The data indicate that OA-NOS (based on immunoreactivity and molecular weight) is similar to ncNOS and that it releases nitric oxide, which may contribute to the inflammation and pathogenesis of cartilage destruction in OA.
Abstract: Classically, osteoarthritis (OA) has been considered a noninflammatory disease. However, the detection of selected inflammatory mediators in osteoarthritic fluid, in the absence of significant inflammatory cell infiltrate, is increasingly appreciated. We sought to identify the inflammatory component in human OA-affected cartilage that may be involved in cartilage damage/destruction. Using Western blot analysis and an antibody to the conserved region of nitric oxide synthase (NOS), we have observed up-regulation of NOS, one of the "key players" of inflammation, in chondrocytes of OA-affected patients. Remarkably, none of the cartilage samples examined from normal joints demonstrated detectable amounts of this NOS. Western blot analysis using the same alpha-NOS antibody indicated that this NOS from OA-affected cartilage (OA-NOS) was larger in size than (and distinct from) transfected human hepatocyte or murine inducible NOS (iNOS) (150 versus 133 kD) and similar in size to neuronal constitutive NOS (ncNOS). Antibodies specific for iNOS showed binding to murine and human iNOS but not to OA-NOS, endothelial constitutive NOS, or ncNOS. Antibodies specific for ncNOS bound to ncNOS and also to OA-NOS, but not to murine or human iNOS or endothelial constitutive NOS. Incubation of OA cartilage in serum-free medium resulted in spontaneous release, for up to 72 h, of substantial amounts of nitrite (up to approximately 80 microM/100 mg wet tissue), which could be inhibited by at least 80% with various inhibitors of iNOS, including inhibitors of protein synthesis and transcription factor NF-kappa B, but which (unlike murine macrophage iNOS) was not sensitive to hydrocortisone or TGF-beta. Exposure of OA-affected cartilage to interleukin 1 beta, tumor necrosis factor-alpha, and lipopolysaccharide resulted in approximately 20-50% augmentation of nitrite accumulation, which was also sensitive to cycloheximide and pyrrolidine dithiocarbamate. Hence, our data indicate that OA-NOS (based on immunoreactivity and molecular weight) is similar to ncNOS and that it releases nitric oxide, which may contribute to the inflammation and pathogenesis of cartilage destruction in OA.
271 citations
TL;DR: Elevated serum levels of COMP may indicate an unfavorable prognosis for rapid joint destruction, whereas elevated 846 epitope indicates a more favorable prognosis.
Abstract: Serum concentrations of specific cartilage and bone molecules reflecting tissue turnover were measured in two well-defined patient groups with early rheumatoid arthritis with distinctly different disease outcome to see if early differences in their levels are prognostic of the rate of joint destruction. Compared with a matched normal population, increased concentrations of cartilage oligomeric matrix protein (COMP) were found in all patients who developed rapid hip joint destruction. In contrast, levels of a putative marker of cartilage aggrecan synthesis, the chondroitin sulfate epitope 846, were increased only in patients with slow joint destruction. Levels of bone sialoprotein (BSP) were increased in both groups, as were levels of the C-propeptide of type II procollagen (CPII), a marker of collagen II synthesis. The increased concentrations of the 846 epitope in patients with slow joint destruction suggest increased aggrecan synthesis. The low levels of the 846 epitope in patients with rapid joint destruction, concomitant with elevated levels of CPII, suggest a selective increase in collagen synthesis. The elevated BSP levels indicate an increased bone turnover in both groups. Thus elevated serum levels of COMP may indicate an unfavorable prognosis for rapid joint destruction, whereas elevated 846 epitope indicates a more favorable prognosis.
251 citations
TL;DR: The results demonstrate that a well-organized cartilage matrix is required as a primary tissue for development of some components of the vertebrate skeleton, but it is not essential for others.
Abstract: Homologous recombination in embryonic stem cells was used to prepare transgenic mice with an inactivated Col2a1 gene for collagen II, the major protein component of the extracellular matrix of cartilage. Heterozygous mice had a minimal phenotype. Homozygous mice developed into fetuses that were delivered vaginally but died either just before or shortly after birth. The cartilage in the mice consisted of highly disorganized chondrocytes with a complete lack of extracellular fibrils discernible by electron microscopy. There was no endochondrial bone or epiphyseal growth plate in long bones. However, many skeletal structures such as the cranium and ribs were normally developed and mineralized. The results demonstrate that a well-organized cartilage matrix is required as a primary tissue for development of some components of the vertebrate skeleton, but it is not essential for others.
TL;DR: Observations indicated that the spheroids formed are of a cartilaginous nature, and that multipotential C3H10T1/2 cells can be induced to undergo cellular differentiation towards chondrogenesis in vitro through culture in a favorable environment.
TL;DR: An impact load was applied to full-depth circular samples of articular cartilage in vitro and the effects of impact energy and velocity on matrix integrity and chondrocyte viability were studied.
TL;DR: Findings indicate the involvement of Hoxa-13 in determining homophilic cell-to-cell adhesiveness that is supposed to be crucial for the cartilage pattern formation.
Abstract: During chick limb development, the Abd-B subfamily of genes in the HoxA cluster are expressed in a region-specific manner along the proximodistal axis. To elucidate the function of Hoxa-13 that is expressed in the autopod during normal limb development, Hoxa-13 was misexpressed in the entire limb bud with a replication-competent retroviral system. Misexpression of Hoxa-13 resulted in a remarkable size reduction of the zeugopodal cartilages as a result of the arrest of cartilage cell growth and differentiation restricted in the zeugopod. This size reduction seems to be attributable to homeotic transformation of the cartilages in the zeugopod to the more distal cartilage, that of the carpus/tarsus. This transformation was specific to Hoxa-13 and was not observed by overexpression of other Hox genes. These results indicate that Hoxa-13 is responsible for switching the genetic code from long bone formation to short bone formation during normal development. When the limb mesenchymal cells were dissociated and cultured in vitro, Hoxa-13-expressing limb mesenchymal cells reassociated and were sorted out from nonexpressing cells. Forced expression of Hoxa-13 at the stage that endogenous Hoxa-13 was not expressed as of yet altered the homophilic cell adhesive property. These findings indicate the involvement of Hoxa-13 in determining homophilic cell-to-cell adhesiveness that is supposed to be crucial for the cartilage pattern formation.
TL;DR: The demonstration of extracellular transglutaminase activity in differentiating cartilage, i.e., cross-linking of osteonectin in situ, shows that tissue transglUTaminase-catalyzed cross- linking is a physiological mechanism for cartilage matrix stabilization.
Abstract: The expression of tissue transglutaminase in skeletal tissues is strictly regulated and correlates with chondrocyte differentiation and cartilage calcification in endochondral bone formation and in maturation of tracheal cartilage (Aeschlimann, D., A. Wetterwald, H. Fleisch, and M. Paulsson. 1993. J. Cell Biol. 120:1461-1470). We now demonstrate the transglutaminase reaction product, the gamma-glutamyl-epsilon-lysine cross-link, in the matrix of hypertrophic cartilage using a novel cross-link specific antibody. Incorporation of the synthetic transglutaminase substrate monodansylcadaverine (amine donor) in cultured tracheal explants reveals enzyme activity in the pericellular matrix of hypertrophic chondrocytes in the central, calcifying areas of the horseshoe-shaped cartilages. One predominant glutaminyl substrate (amine acceptor) in the chondrocyte matrix is osteonectin as revealed by incorporation of the dansyl label in culture. Indeed, nonreducible osteonectin-containing complexes of approximately 65, 90, and 175 kD can be extracted from mature tracheal cartilage. In vitro cross-linking of osteonectin by tissue transglutaminase gives similar products of approximately 90 and 175 kD, indicating that the complexes in cartilage represent osteonectin oligomers. The demonstration of extracellular transglutaminase activity in differentiating cartilage, i.e., cross-linking of osteonectin in situ, shows that tissue transglutaminase-catalyzed cross-linking is a physiological mechanism for cartilage matrix stabilization.
TL;DR: The modulation of beta 1 integrin expression noted in vitro and in situ indicates that chondrocytes are capable of regulated expression of Beta 1 integrins and suggests that beta 1integrins may play an important role in mediating chONDrocyte-extracellular matrix interactions in cartilage.
TL;DR: It is indicated that PDGF is expressed during normal human fracture repair, and the in vitro data suggest thatPDGF is likely to be an important local regulator in this process.
TL;DR: A small size indentation instrument is developed for the quantification of cartilage stiffness under arthroscopic control and the correlation between two repeated measurements at the measurement sites, used to evaluate the reproducibility, was linear.
TL;DR: It is demonstrated that transplantation of transduced chondrocytes onto the articular surface protects cartilage from IL-1-induced extracellular matrix degradation and is resistant to IL1- induced proteoglycan degradation over 10 d of sustained organ culture.
Abstract: Gene therapy used in the context of delivering a therapeutic gene(s) to chondrocytes offers a new approach for treating chondrocyte-mediated cartilage degradation associated with various human arthropathies including osteoarthritis. In this study, gene delivery to human osteoarthritis chondrocytes in monolayer culture was demonstrated using two adenoviral vectors (Ad.CMVlacZ and Ad.RSVntlacZ) carrying the Escherichia coli fi-galactosidase marker gene, and a third vector (Ad.RSV hL-ira) containing the cDNA for human interleukin-1 receptor antagonist. At an moi of 103 plaque-forming units/chondrocyte, > 90% of the infected cells stained positive for E. coli j3-galactosidase activity, indicating a high efficiency of transduction. Genetically modified chondrocytes were then transplanted onto the articular surface ofosteoarthritic cartilage organ cultures with and without the underlying subchondral bone. Both in situ staining ofthe cartilage organ cultures forE. coli P-galactosidase activity and examination by scanning electron microscopy indicated that the transplanted chondrocytes adhered and integrated into the articular surface and continued to express transgenic protein. Chondrocytes transduced with Ad.RSV hIL-ira and seeded onto the surface of osteoarthritic cartilage secreted high levels of biologically active IL-1 receptor antagonist. The Ad.RSV hIL-ira-treated cartilage samples were resistant to ILl-induced proteoglycan degradation over 10 d of sustained organ culture. These data demonstrate that transplantation of transduced chondrocytes onto the articular surface protects cartilage from IL-i-induced extracellular matrix degradation. (J. Clin. Invest. 1995. 96:2454-2460.) Key words: arthritis * gene therapy * interleukin-1 receptor antagonist adenovirus
TL;DR: Chondrocyte-collagen grafts were arthroscopically implanted and resulted in improved cartilage healing in extensive defects, however, the structural organization of the surface layers was inadequate and suggested poor long-term durability.
TL;DR: A detailed analysis of M‐twist expression patterns from day 7 post coitum (p.c.) to day 18 p.c. indicates a more general function of the Drosophila twist gene, suggesting additional tissue specific functions.
Abstract: The murine homologue of the Drosophila twist gene has been shown to be essential for head mesenchyme formation and to act as an inhibitor of muscle differentiation. This paper presents a detailed analysis of M-twist expression patterns from day 7 post coitum (p.c.) to day 18 p.c., indicating a more general function of the M-twist gene. At day 7 p.c., M-twist is expressed in the mesoderm outside the primitive streak. Later M-twist message is predominantly found in the somites, the head mesenchyme, the branchial arches, the limbs, and in the mesenchyme underneath the epidermis. Beginning at day 8 p.c., M-twist is mainly expressed in undifferentiated cells committed to muscle and cartilage development: this expression is consistent with a suggested role of M-twist in inhibiting overt muscle and cartilage differentiation. However, during organogenesis, M-twist is expressed in several areas of mesenchyme-epithelia interactions, suggesting additional tissue specific functions.
TL;DR: The diffusion chamber is validated as an experimental system to study human osteogenesis using appropriately primed cell populations based on the results of this study on human osteoprogenitor cell populations derived from trabecular bone explants or marrow suspensions.
Patent•
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TL;DR: In this article, the process of producing BMP-9 proteins and the processes for producing them are described and discussed. The proteins may be used in the treatment of bone and cartilage defects and in wound healing and related tissue repair, and in hepatic growth and function.
Abstract: Purified BMP-9 proteins and processes for producing them are disclosed. The proteins may be used in the treatment of bone and cartilage defects and in wound healing and related tissue repair, and in hepatic growth and function.
Journal Article•
TL;DR: High frequency ultrasonic images obtained in vitro provide highly accurate and reproducible measurements of the thickness and subsurface characteristics of normal and OA articular cartilage.
Abstract: OBJECTIVE Osteoarthritis (OA) is characterized by progressive loss of articular cartilage in the involved joint. Accurate, reproducible measurement of the thickness of the cartilage in vivo, however, is difficult. Because development of an ultrasonic imaging device for intraarticular use is feasible and would permit acquisition of information that could complement the assessment of articular cartilage made at arthroscopy, we evaluated the efficacy of high frequency ultrasound in assessing the thickness and subsurface characteristics of normal and OA cartilage. METHODS Blocks of human femoral cartilage and subchondral bone and chips of cartilage alone were examined in vitro with an experimental 25 MHz pulse-echo ultrasound scanner that portrayed cross sections of the cartilage as B-mode images. The gross and histologic appearance of the articular surface was used to identify specimens of unblemished, normal cartilage and OA cartilage. The speed of sound in cartilage, determined from measurements of cartilage thickness and sound transmission, was related to its biochemical composition. RESULTS The speed of sound in normal cartilage (1658 +/- 185 m/s, n = 27) was greater than that in OA cartilage (1581 +/- 148 m/s, n = 40, p = 0.06), but was not related to the cartilage water content or the concentration of uronic acid or hydroxyproline. Images of normal cartilage showed a smooth echo band at the tissue surface with a hypoechoic matrix; in scans of fibrillated cartilage the width of this band was proportional to the depth of fibrillation (r = 0.78). Ultrasonic and histologic measurements of OA cartilage thickness were closely correlated (r = 0.87) and the mean coefficient of variation for repeated measurements was 2%. CONCLUSION High frequency ultrasonic images obtained in vitro provide highly accurate and reproducible measurements of the thickness and subsurface characteristics of normal and OA articular cartilage.
TL;DR: Exposure of intact cartilage to SLN caused specific, molecular-level degradation of matrix molecules, which resulted in changes in the swelling behavior and marked deterioration of functional physical properties of the tissue.
Abstract: Objective. To determine the effects of stromelysin treatment on biochemical, histologic, and swelling characteristics of intact cartilage explants and to correlate these effects with changes in the functional physical properties of the tissue.
Methods. Bovine articular cartilage explants were cultured for up to 3 days in the presence or absence of recombinant human stromelysin (SLN). Damage to matrix proteoglycans and collagens was assessed and characterized by N-terminal sequencing and Western blot analysis, respectively. Explants were mechanically tested to assess the ability of the tissue to withstand cyclic and static compressive loads.
Results. Treatment with SLN resulted in a time-and dose-dependent loss of proteoglycans from cartilage explants, with significant loss seen after 3 days of exposure to 20 nM SLN. Histology indicated that initial loss of proteoglycans occurred in regions near the tissue surface and proceeded inward with increasing time of SLN exposure. SLN treatment resulted in degradation of matrix collagen types IX and II, and a concomitant increase in tissue swelling. This matrix degradation resulted in severe alterations in functional physical properties of the tissue, including compressive stiffness. The initial, focal loss of proteoglycans that resulted from SLN treatment was most accurately detected with highfrequency streaming potential measurements.
Conclusion. Exposure of intact cartilage to SLN caused specific, molecular-level degradation of matrix molecules, which resulted in changes in the swelling behavior and marked deterioration of functional physical properties of the tissue.
Journal Article•
TL;DR: In vivo, lifelong moderate and probably even strenuous joint use does not cause cartilage degeneration in normal animal joints, i.e., joints with normal articular surfaces, alignment, stability, innervation, and muscle control, but static loading or the absence of loading causes matrix degradation and eventually loss of joint function.
Abstract: Recent investigations have distinguished 3 different patterns of articular cartilage use that have different consequences: normal use, marked decrease use (disuse), and use that damages the tissue (abuse). In vitro cyclic loading of cartilage in the physiologic range stimulates matrix synthesis. In vivo, lifelong moderate and probably even strenuous joint use does not cause cartilage degeneration in normal animal joints, i.e., joints with normal articular surfaces, alignment, stability, innervation, and muscle control. In contrast, static loading or the absence of loading causes matrix degradation and eventually loss of joint function. Abuse of normal joints by single or repetitive impact loads can lead to progressive degeneration of the articular surface. Normal use of abnormal joints, in particular joints with incongruous articular surfaces, malalignment, instability, or disturbances of joint or muscle innervation may also increase the risk of degenerative joint disease.
TL;DR: Immunolocalization studies indicate that perlecan, once thought to be a unique component of the basement membranes, is more widely distributed and is an important components of the cartilage matrix, where it may provide for cell adhesion to the matrix.
Abstract: Aggrecan, a chondroitin/keratan sulfate-containing proteoglycan, is a major component of cartilaginous tissues. Immunolocalization studies, using antibodies directed to perlecan, a heparan sulfate proteoglycan first detected in basement membranes, and laminin (another major component of basement membranes), indicate that perlecan and laminin are also present in the matrices of hyaline cartilage in the nasal septum, the articular surface of the bone and the growth plate of the developing bone. Consequently, we used antibodies to both aggrecan and perlecan to characterize their synthesis and secretion by primary cultures of chondrocytes derived from the rat chondrosarcoma. Chondrocytes were pulsed for 20 minutes with [35S]methionine and then chased for up to six hours. The radiolabeled perlecan and aggrecan were immunoprecipitated and analyzed by SDS-PAGE. The results show that chondrocytes synthesize precursor proteins to both proteoglycans, but that only the aggrecan precursor protein is secreted as a proteoglycan. Perlecan was also secreted but with less posttranslational modifications than aggrecan. Northern blot analyses of the RNAs from immortalized rat chondrocytes indicated that the major mRNA encoding for perlecan was approximately 13 kb in length, similar in size to that expressed by other cell types, which synthesize 400 kDa core protein perlecan. Analyses of the proteoglycan fractions from the extracts of bovine articular surface indicated that perlecan in this tissue contains both chondroitin and heparan sulfate side-chains. Purified perlecan and laminin were found to promote attachment of immortalized rat chondrocytes in vitro. These studies indicated that perlecan, once thought to be a unique component of the basement membranes, is more widely distributed and is an important component of the cartilage matrix, where it may provide for cell adhesion to the matrix.
TL;DR: The observed changes in material properties demonstrate that relatively short periods of joint instability result in significant changes in the flow‐independent viscoelastic behavior of articular cartilage, as well as in the intrinsic stiffnesses in compression and shear.
TL;DR: The baboon represents the most appropriate animal model of normal human hip articular cartilage because it exhibits significant topographical variations in the femoral head and acetabulum, and between these two bone structures.
Abstract: The material properties of normal adult articular cartilage were determined in the femoral head and acetabulum of baboons, dogs, and bovines, and were compared with those of normal human hip cartilage. In situ creep and recovery indentation experiments were performed using an automated creep indentation apparatus. To curvefit the entire creep curve, a numerical algorithm based on biphasic finite element methods and nonlinear optimization was developed. This effort represents the first successful use of 100% of the creep indentation curve to obtain the mechanical properties of normal articular cartilage. The results show that material properties of articular cartilage exhibit significant topographical variations in the femoral head and acetabulum, and between these two bone structures. Furthermore, significant differences exist in the mechanical properties of hip cartilage among the 4 species. Specifically, in all species the smallest aggregate modulus is found in the inferior aspect of the femoral head. Among all species, human hip cartilage is the stiffest in all test sites; bovine tissue is the softest. Human tissue has the smallest Poisson's ratio and permeability in all test sites. The aggregate modulus of human hip cartilage is closely resembled by that of baboon hip cartilage. Anatomically, canine and baboon hips exhibit similar characteristics to the human hip joint; the bovine hip joint is distinctly different. Based on this study's data, the baboon represents the most appropriate animal model of normal human hip articular cartilage.