PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “CARTILAGE, ARTICULAR”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources

Articular cartilage cells immortalized by a temperature sensitive mutant of SV40 large T antigen survive and form cartilage tissue in articular cartilage environment.

A chondrogenic cell line, TC6, was established by using cells derived from articular cartilage of transgenic mice harboring a temperature-sensitive mutant simian virus (SV) 40 large T-antigen gene. TC6 cells express genes encoding proteins related to cartilage phenotypes such as type II collagen. To examine the in vivo behavior of the TC6 cells, these cells were implanted into cavity-shaped full-thickness defects made in the articular cartilage of the central part of the patellar grooves of mouse femora. One week after implantation, the morphology of the cells was still fibroblastic but these cells were just about to start to form a cartilage-like matrix. By 6 weeks after implantation, the cells had produced abundant cartilaginous matrix and their morphology became closer to that of authentic chondrocytes. This was in sharp contrast to the fibroblastic morphology of these cells in an in vitro environment even after long-term culture. These observations indicate that a cartilage-matrix environment provides a scaffold for the TC6 cells to form cartilage tissues. Our data show that the genetically engineered chondrocytic cell line, TC6, can form a cartilage-like matrix in vivo.

Animals↗

Expression of ADAMTS homologues in articular cartilage.

Articular chondrocytes possess the capacity to express a number of ADAM (A Disintegrin And Metalloproteinase) family members, thereby implicating a role for such proteins in the turnover of cartilage extracellular matrix molecules. Recently, the sequence for the human orthologue of an "aggrecanase" isolated from bovine nasal cartilage has been elucidated, and the recombinant protein product shown to be capable of cleaving aggrecan specifically at the relevant peptide bonds which are hydrolyzed in situ during cartilage degradation. The sequence for the human "aggrecanase" exhibits homology with that of murine ADAMTS-1, an ADAM with thrombospondin type I motifs. In the present study we have identified additional ADAMTS homologues and have examined their mRNA expression profiles in freshly excised human articular cartilage and in human cartilage explant cultures stimulated with IL-1, TNF-alpha, or retinoic acid, agents which enhance "aggrecanase" activity in vitro. Significantly, cartilage exposed to retinoic acid showed a marked increase in the release of "aggrecanase"-generated aggrecan catabolites with no concomitant increase in mRNA levels for any of the ADAMTS homologues investigated. These findings indicate that enhanced "aggrecanase" activity, which may be attributed to known ADAMTS homologues, may be predominantly regulated by post-transcriptional mechanism(s), and may raise the possiblility for the existence of other as yet unidentified "aggrecanase(s)."

Aged↗

The role of mandibular condylar cartilage in articular cartilage repair.

The articular hyaline cartilage of synovial joints has a very limited capacity for repair after injury. In contrast, the mandibular condylar cartilage of the temporomandibular joint possesses as intrinsic potential for regeneration. This study aimed to test the hypothesis that cultured allografts of mandibular condylar cartilage could be used to promote biological repair of injured orthotopic joint surfaces. Using a primate animal model, cultures of mandibular condylar cartilage cells were grafted into surgically created defects in a recipient hyaline cartilage joint surface. Articular wound healing was assessed macroscopically and histologically over a postoperative period of 52 weeks. Mandibular condylar cartilage cells scheduled for allogenous transplantation were initially characterised in vitro. Expansion of primary colonies in organ culture provided the allogenic cellular material for in vivo grafting. Grafting of osteochondral articular wounds with 5-week cultures of mandibular cartilage cells led to wound regeneration with complete reconstitution of articular surface continuity by 52 weeks. There was novel synthesis of cartilage collagens and sulphated glycosaminoglycans within the repair tissue and no evidence of immunological rejection. Healing of grafted defects was thought to occur by a combination of donor cell proliferation and ingress of host mesenchymal cells. In contrast, grafted control wounds underwent largely fibrous repair with incomplete articular regeneration. In conclusion, transplanted allografts of cultured mandibular condylar cartilage appeared to have the ability, in this primate model, to promote cartilaginous repair and regeneration of orthotopic articular wounds.

Animals↗

Mechanical regulation of mitogen-activated protein kinase signaling in articular cartilage.

Articular chondrocytes respond to mechanical forces by alterations in gene expression, proliferative status, and metabolic functions. Little is known concerning the cell signaling systems that receive, transduce, and convey mechanical information to the chondrocyte interior. Here, we show that ex vivo cartilage compression stimulates the phosphorylation of ERK1/2, p38 MAPK, and SAPK/ERK kinase-1 (SEK1) of the JNK pathway. Mechanical compression induced a phased phosphorylation of ERK consisting of a rapid induction of ERK1/2 phosphorylation at 10 min, a rapid decay, and a sustained level of ERK2 phosphorylation that persisted for at least 24 h. Mechanical compression also induced the phosphorylation of p38 MAPK in strictly a transient fashion, with maximal phosphorylation occurring at 10 min. Mechanical compression stimulated SEK1 phosphorylation, with a maximum at the relatively delayed time point of 1 h and with a higher amplitude than ERK1/2 and p38 MAPK phosphorylation. These data demonstrate that mechanical compression alone activates MAPK signaling in intact cartilage. In addition, these data demonstrate distinct temporal patterns of MAPK signaling in response to mechanical loading and to the anabolic insulin-like growth factor-I. Finally, the data indicate that compression coactivates distinct signaling pathways that may help define the nature of mechanotransduction in cartilage.

Animals↗

TGF-beta/Smad3 signals repress chondrocyte hypertrophic differentiation and are required for maintaining articular cartilage.

Endochondral ossification begins from the condensation and differentiation of mesenchymal cells into cartilage. The cartilage then goes through a program of cell proliferation, hypertrophic differentiation, calcification, apoptosis, and eventually is replaced by bone. Unlike most cartilage, articular cartilage is arrested before terminal hypertrophic differentiation. In this study, we showed that TGF-beta/Smad3 signals inhibit terminal hypertrophic differentiation of chondrocyte and are essential for maintaining articular cartilage. Mutant mice homozygous for a targeted disruption of Smad3 exon 8 (Smad3(ex8/ex8)) developed degenerative joint disease resembling human osteoarthritis, as characterized by progressive loss of articular cartilage, formation of large osteophytes, decreased production of proteoglycans, and abnormally increased number of type X collagen-expressing chondrocytes in synovial joints. Enhanced terminal differentiation of epiphyseal growth plate chondrocytes was also observed in mutant mice shortly after weaning. In an in vitro embryonic metatarsal rudiment culture system, we found that TGF-beta1 significantly inhibits chondrocyte differentiation of wild-type metatarsal rudiments. However, this inhibition is diminished in metatarsal bones isolated from Smad3(ex8/ex8) mice. These data suggest that TGF-beta/Smad3 signals are essential for repressing articular chondrocyte differentiation. Without these inhibition signals, chondrocytes break quiescent state and undergo abnormal terminal differentiation, ultimately leading to osteoarthritis.

Animals↗

Collagen II from articular cartilage and annulus fibrosus. Structural and functional implication of tissue specific posttranslational modifications of collagen molecules.

Collagen II was isolated and characterized from hyaline cartilage (articular cartilage) and fibro-cartilage (annulus fibrosus). Collagen II from the latter tissue has a substantially higher degree of hydroxylation and glycosylation than that isolated from articular cartilage. The higher degree of posttranslational modification was associated with a slower electrophoretic mobility, a greater resistance to mammalian collagenase digestion and a higher thermal stability. An increase of glycosylation accelerates the initial steps in fibril formation of collagen molecules but slows down the following lateral growth. The newly formed aggregates of collagen II from annulus fibrosus consisted of fibrils with a smaller diameter.

Amino Acid Sequence↗

Articular cartilage preservation and storage. I. Application of tissue culture techniques to the storage of viable articular cartilage.

Articular cartilage slice explants were stored under various conditions, including freezing-thawing at various rates by using dimethyl sulfoxide (DMSO) as a cryoprotective agent, incubating in standard tissue culture medium (MEM Eagle:NCTC 135:15% fetal calf serum) in 5% CO2 and air at 4 degrees, 21 degrees, and 37 degrees C, and incubating in standard tissue culture medium containing 200 micrograms/ml alpha-tocopherol (vitamin E) at 37 degrees C after first ascertaining a dose-response curve of vitamin E. Results indicated that articular cartilage slice explants did not survive freezing or storage at 4 degrees and 21 degrees C as measured by 35S uptake. When stored at 37 degrees C in standard tissue culture in 5% CO2 and air, the slice explants remained viable for up to 60 days. The addition of alpha-tocopherol to the medium resulted in significantly less release of previously incorporated 35Sin stored cartilage slices and significantly less reduction of the amount of hexosamine present in the stored explants. alpha-Tocopherol in the medium also preserved safranin O staining. Thus, the application of tissue culture techniques to the storage of articular cartilage made it possible to preserve cartilage slice explants in a viable, biochemically "normal" state.

Animals↗

Immunohistochemical detection and immunochemical analysis of type II collagen degradation in human normal, rheumatoid, and osteoarthritic articular cartilages and in explants of bovine articular cartilage cultured with interleukin 1.

Articular cartilage destruction and loss of function in arthritic diseases involves proteolytic degradation of the connective tissue matrix. We have investigated the degradation of cartilage collagen by developing immunochemical methods that permit the identification and analysis of type II collagen degradation in situ. Previously, a technique to specifically identify type II collagen degradation in situ in articular cartilage did not exist. These methods utilize a polyclonal antiserum (R181) that specifically reacts with unwound alpha-chains and CNBr-derived peptides, alpha 1(II)CB11 and alpha 1(II)CB8, of human and bovine type II collagens. The experimental approach is based on the fact that when fibrillar collagens are cleaved the helical collagen molecule unwinds, exposing hidden epitopes. Here we demonstrate the use of R181 in studying type II collagen degradation in bovine articular cartilage that has been cultured with or without IL-1 and in human normal, rheumatoid, and osteoarthritic articular cartilages. Compared to cartilages either freshly isolated or cultured without IL-1, bovine cartilage cultured with IL-1 for 3-5 d showed an increase in both pericellular and intercellular immunohistochemical staining. Extracts of these cartilages contained type II collagen alpha chains that were increased in amount after culture with IL-1 for 11 d. In addition, culture with IL-1 resulted in the appearance of alpha chain fragments of lower molecular weight. All human arthritic tissues examined showed areas of pronounced pericellular and territorial staining for collagen degradation as compared with non-diseased tissues, indicating that chondrocytes are responsible in part for this degradation as compared with non-diseased tissues. In most cases rheumatoid cartilage was stained most intensely at the articular surface and in the deep and mid-zones, whereas osteoarthritic cartilage usually stained more in the superficial and mid-zones, but less intensely. Distinct patterns of sites of collagen degradation reflect differences in collagen destruction in these diseases, suggesting possible different sources of chondrocyte activation. These experiments demonstrate the application of immunological methods to detect collagen degradation and demonstrate an increase of collagen degradation in human arthritides and in IL-1-treated viable bovine cartilage.

Animals↗

[Glucosamine: its importance for the metabolism of articular cartilage. 2. Studies on articular cartilage].

In healthy individuals there exists a balance between cartilage proteoglycan synthesis and degradation. In arthrotic cartilage this metabolic balance is deteriorated in spite of a sometimes enhanced proteoglycan synthesis, since the catabolic rate exceeds the anabolic rate corresponding to the severity of the disease. The extracellular organic matrix of the cartilage is destroyed. With different experimental models it could be demonstrated, that the non steroidal anti-inflammatory drugs commonly used in the treatment of arthrosis inhibit the synthesis of mucopolysaccharides, intensify the already existing metabolic disorder, prevent a normalization of cartilage composition and thus impair the function of the cartilage. Glucosamine on the other hand increases in a dose-dependent way the ability of cartilage to synthesize both sulfated mucopolysaccharides and protein, thus restoring the catabolic-anabolic balance of the cartilage.

Animals↗

Experimental studies on half-joint transplantation. Antigenicity of fresh allografted articular cartilage and changes in the articular cartilage.

This study was undertaken to examine the fate of articular cartilage in isogenic half-joint grafts implanted after storage by two-stage freezing. The antigenicity was evaluated quantitatively with regard to humoral and cellular immunological responses: none was seen in allogenic cartilage grafts. In the half-joint transplantations, the antigenicity of the cartilage need not be considered; only the antigenicity of cortical and cancellous bone must be reduced. Histologically, half-joint grafts stored at -196 degrees C were superior to fresh allografts. Two-stage freezing, therefore, appears to be useful for the storage of articular cartilage.

Animals↗

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

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.

Animals↗

Influence of pregnancy on gene expression in rabbit articular cartilage.

OBJECTIVE: Articular cartilage is known to be influenced by estrogen and the pregnancy-associated hormone, relaxin, in vitro. Such observations have raised the possibility that articular cartilage in females may be subjected to unique regulatory influences by such hormones in vivo. The purpose of this study was to evaluate mRNA levels for several relevant molecules in the articular cartilage of pregnant and non-pregnant rabbits. DESIGN: Total RNA was extracted from New Zealand White rabbit knee articular cartilage using the TRIspin method. The total RNA was reverse transcribed and analysed by the sensitive molecular technique of semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) using rabbit specific primer sets. RESULTS: Total RNA yield from articular cartilage from primigravida rabbits was reduced to 65% of age-matched control values (P = 0.0003); however the yield from multiparous animals was not significantly depressed. In both cases, DNA yields were not affected by pregnancy. There was a general tendency for depressed mRNA levels for most genes investigated in cartilage from pregnant animals. Articular cartilage from multiparous rabbits showed a significant decrease in mRNA levels for relevant molecules such as type II collagen, biglycan, collagenase and tissue inhibitors of metalloproteinases (TIMP)-1, as well as necrosis factor-alpha (TNF-alpha), inducible nitric oxide synthase (iNOS) and cyclo-oxygenase 2 (COX-2). Transcripts for collagenase and lumican were significantly lower in cartilage from primigravida rabbits. Transforming growth factor beta 1 (TGF-beta 1) transcript levels were significantly decreased in both pregnant groups. In contrast, basic fibroblast growth factor (bFGF) and insulin-like growth factor-2 (IGF-2) mRNA levels were significantly decreased in cartilage from primigravida rabbits, whereas transcripts for these molecules were upregulated in the cartilage of multiparous rabbits. CONCLUSIONS: The present study demonstrates that regulation of RNA levels in articular cartilage during pregnancy is complex and is influenced by the parity and/or the skeletal maturity of the animals.

Animals↗

Repair of large full-thickness articular cartilage defects with allograft articular chondrocytes embedded in a collagen gel.

Full-thickness articular cartilage defects are a major clinical problem; however, presently there is no treatment available to regeneratively repair these lesions. The current therapeutic approach is to drill the base of the defect to expose the subchondral bone with its cells and growth factors. This usually results in a repair tissue of fibrocartilage that functions poorly in the loaded joint environment. The use of phenotypically appropriate chondrocytes embedded in a collagen gel delivery vehicle may provide a method that could be used to repair full-thickness articular cartilage defects with functionally satisfactory hyaline cartilage. Allograft articular chondrocytes embedded in a type I collagen gel were transplanted into large (6 x 3 x 3 mm), full-thickness articular cartilage defects in condylar and patellar weight-bearing surfaces to develop clinically applicable methods to repair articular cartilage defects. Chondrocytes were isolated from the articular cartilage of 4-week-old New Zealand rabbits and embedded in type I collagen gels. This composite was transplanted into a full-thickness defect on the medial femoral condyle and patellar groove of adolescent host rabbits. The repair cartilage was assessed histologically by a semiquantitative scoring system and biomechanically with a microindentation technique of specimens 4-48 weeks after chondrocyte transplantation. Defects in both locations were repaired with histologically apparent hyaline cartilage observed from as early as 4 weeks until 48 weeks after transplantation. The repair cartilage in the medial femoral condyle was more irregular than in the patellar groove, but in all other respects was similar. The grafted tissue did not remodel and differentiate into the morphological zones seen in normal articular cartilage. No tidemark or subchondral bony plate formed even 48 weeks after transplantation. Biomechanically, the repaired cartilage demonstrated indentation values similar to normal articular cartilage 12 weeks after transplantation and remained the same 48 weeks after transplantation. By contrast, the control (i.e., empty) defects healed with tissue that exhibited very poor metachromatic staining and exhibited very high indentation values. Incomplete bonding of the repair tissue to the normal cartilage was seen, and the surface was significantly irregular with major discontinuities. These observations provide the basis for considering the use of allograft articular chondrocytes to repair articular cartilage defects in the weight-bearing regions of the knee.

Animals↗

New developments in the pathogenesis of articular cartilage calcification.

Articular cartilage, unlike growth plate cartilage, is specialized to not undergo matrix calcification. However, articular cartilage mineralization, in the form of CPPD (chondrocalcinosis) and hydroxyapatite crystals, frequently accompanies and complicates osteoarthritis and aging. Recent work has demonstrated that certain features of growth cartilage development and mineralization are shared in degenerative cartilage. These include chondrocyte proliferation, hypertrophy and increased apoptosis. Moreover, parathyroid hormone related protein (PTHrP), one of the central mediators of endochondral development, is abundant in osteoarthritic cartilage. Cartilage PPi elaboration and cytosolic transglutaminase activity are markedly increased with aging. Only recently have the molecular identities been defined for the chondrocyte inorganic pyrophosphate (PPi)-generating isozymes of the phosphodiesterase nucleotide pyrophosphatase (PDNP) family (including PC-1 and B10), and for transglutaminase in articular cartilage. This review focuses on the evolving understanding of the potential roles, in articular cartilage calcification, of PTHrP, PDNP family enzymes, PPi metabolism, and transglutaminase activity.

Age Factors↗

Surgical alternatives for treatment of articular cartilage lesions.

Articular cartilage injuries in the knee are common; fortunately, full-thickness articular cartilage defects constitute only a small portion of this group. These lesions may be incidentally encountered during ligament or meniscal surgery, having been silent or asymptomatic for an unknown period of time. However, when they are large and symptomatic, the surgeon may choose from a wide array of techniques available for treatment. The relatively small number of natural history studies regarding full-thickness articular surface lesions complicates the decision-making process. Accurate evaluation and classification of the anatomic defect aids in the development of a clinical algorithm for treatment. Surgical techniques are either reparative or restorative in nature. Reparative techniques fall short of complete reestablishment of the articular cartilage; however, the resultant repairs may remain quite functional for varying periods of time. Restorative techniques attempt to reestablish the native articular surface. To date, no peer-reviewed, prospective, randomized, controlled studies of operative versus nonoperative treatment for full-thickness articular cartilage lesions have been published. Even though the long-term results of surgical treatment for full-thickness articular surface lesions remain unknown, the early results are encouraging.

Adult↗

Developmental distribution of collagen type XII in cartilage: association with articular cartilage and the growth plate.

Collagen type XII is a member of the fibril-associated collagens and is characterized by a short triple-helical domain with three extended noncollagenous NC3 domains. Previous studies suggested that collagen XII is a component of cartilage but little is known about its spatial-temporal distribution. This study uses a polyclonal antibody to the purified NC3 domain to investigate its developmental distribution in rat forelimb. Collagen XII was present at the joint interzone on embryonic day 16 (E16d) and restricted to the presumptive articular cartilage by E18d. Labeling of the articular surface intensified as development progressed postnatally (day 1 [1d] to 28d) and extended approximately six cell diameters deep. In juvenile rats, collagen XII antibodies also labeled the longitudinal and transverse septa of stacked chondrocytes in the growth plate. However, collagen XII was not associated at any developmental stage with the cartilaginous secondary ossification center and was only weakly expressed in epiphyseal cartilage. Ultrastructural localization of the NC3 domain epitope showed labeling of the surface of collagen II fibrils both in tissue and in isolated fibrils. The results presented provide further evidence that articular cartilage differs substantially from the underlying epiphyseal cartilage and that different chondrocytic developmental fates are reflected in the composition of their extracellular matrix starting early in development. In addition, collagen XII was distributed in areas of cartilage with more organized fibril orientation and may have a role in promoting alignment or stabilizing such an organization, thereby creating a matrix capable of withstanding load-bearing forces.

Animals↗

Functional replacement of oxygen by other oxidants in articular cartilage.

OBJECTIVE: Articular cartilage chondrocytes consume remarkably little O(2) in comparison with most other animal cells; glycolysis forms the principal source of ATP in this cartilage. Although not lethal for many days, imposition of anoxia immediately lowers intracellular ATP, inhibits rates of glycolysis, and prevents articular chondrocytes from producing extracellular matrix macromolecules. This study was undertaken to investigate the role of O(2) in articular chondrocyte metabolism. METHODS: We examined the effects of oxygen and of several other classes of exogenous oxidants, i.e., 1) the dyes methylene blue and 2,6-dichlorophenol-indophenol, 2) the iron (III) complex ferricyanide, and 3) the keto-acids oxaloacetate and pyruvate (and phosphoenolpyruvate, a metabolic precursor of pyruvate), on rates of glycolysis and of sulfate incorporation by bovine articular cartilage in vitro. RESULTS: Lactate production was lowest under conditions of anoxia and was stimulated severalfold by addition of O(2) (air-saturated medium). Under strict anoxia, other oxidants restored lactate production to rates at least comparable with those seen in aerobic controls; under aerobic conditions, they had little effect. Oxygen and all of the other oxidants examined stimulated sulfate incorporation more strongly than lactate production. The compounds that promoted glycolysis and hence sulfate incorporation in cartilage under anoxia were themselves reduced; that is, they functioned as oxidants in lieu of O(2). CONCLUSION: For normal function, articular cartilage appears to require exogenous oxidants to stimulate glycolysis and produce ATP and extracellular matrix. Under physiologic conditions, oxygen acts as this oxidant, but its role can be adequately assumed by other agents.

Adenosine Triphosphate↗