Clinical implications of cartilage metabolism in arthritis.
The ability of articular cartilage to withstand repeated mechanical loading with relatively little wear over a lifetime results from the properties of the extracellular matrix (ECM) and the optimal function of the chondrocytes which are responsible for the synthesis and presumably maintenance of this ECM. The properties of the ECM are accounted for by the relationship of the major aggregating, polyanionic, negatively charged proteoglycans with their potent viscoelastic properties to the network of collagens and several noncollagenous proteins. The major collagen (type II) interacts with type IX collagen in a highly specific manner. Type IX collagen has a chondroitin sulfate side chain and can also bind to the aggregating proteoglycans through a basic amino terminal domain. In inflammation, injury and probably repeated wear, function of the chondrocytes is disturbed, mediated by the action of potent cytokines, which results in release of degradative enzymes and alterations in the pattern of synthesis of the ECM. Identification of the critical cytokines and the sequence of events that result from their action should provide the basis for rational prophylaxis and therapy of disorders such as osteoarthritis and rheumatoid arthritis. Articular cartilage has unique mechanical properties which permit repeated mechanical loading with relatively little wear over a lifetime. These properties result from the special character of the extracellular matrix (ECM) and optimal functioning of the component cells (chondrocytes) which are responsible for the synthesis and presumably, maintenance of this matrix. Articular chondrocytes survive and perform these critical functions in an anaerobic environment remote from the vasculature and must derive their nutrition from the synovial fluid.(ABSTRACT TRUNCATED AT 250 WORDS)
Krane
S M
SM
Department of Medicine, Harvard Medical School, Massachusetts General Hospital, Boston 02114.
Goldring
M B
MB
D000818:Animals; D001168:Arthritis / Q000378:metabolism*; D002358:Cartilage, Articular / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D011506:Proteins / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism
D011506:Proteins; D011509:Proteoglycans; D003094:Collagen