Clinical implications of cartilage metabolism in arthritis.

S M Krane, M B Goldring
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Abstract

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)

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关节炎中软骨代谢的临床意义。
关节软骨在一生中承受重复机械负荷而磨损相对较小的能力来自细胞外基质(ECM)的特性和软骨细胞的最佳功能,这些细胞外基质负责合成并可能维持这种ECM。ECM的性质是由主要聚集、聚阴离子、带负电荷的蛋白聚糖与胶原蛋白和几种非胶原蛋白网络的强粘弹性的关系决定的。主要胶原蛋白(II型)与IX型胶原蛋白以高度特异性的方式相互作用。IX型胶原具有硫酸软骨素侧链,也可以通过碱性氨基末端结构域与聚集的蛋白聚糖结合。在炎症、损伤和可能的反复磨损中,软骨细胞的功能受到干扰,由强效细胞因子的作用介导,导致降解酶的释放和ECM合成模式的改变。鉴定关键细胞因子及其作用所导致的事件顺序,应为合理预防和治疗骨关节炎和类风湿关节炎等疾病提供基础。关节软骨具有独特的机械性能,允许在一生中重复机械载荷相对较小的磨损。这些特性源于细胞外基质(ECM)的特殊特性和负责合成并可能维持这种基质的组成细胞(软骨细胞)的最佳功能。关节软骨细胞在远离脉管系统的厌氧环境中存活并发挥这些关键功能,必须从滑液中获取营养。(摘要删节250字)
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