Recent developments in cartilage research: matrix biology of the collagen II/IX/XI heterofibril network
Recent developments in cartilage research: matrix biology of the collagen II/IX/XI heterofibril network
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DOI：
10.1042/bst0300894
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发表时间：
2002-11-01
影响因子：
3.9
通讯作者：
Weis, MA
中科院分区：
文献类型：
--
作者：
Eyre, DR;Wu, JJ;Weis, MA
随着努力发现治疗或预防骨关节炎的疾病缓解药物，对软骨的研究正在加强。软骨胶原蛋白结构的蛋白水解损伤是退行性关节病发病机制的一个关键组成部分，而且可能是早期组成部分。在这里，我们总结了关于软骨胶原原纤维独特异聚结构的最新发现，包括胶原蛋白 IX（一种共价键合的原纤维适配器分子）的关键作用。涉及所有三种成分基因产物的高度特异性的交联位点模式强烈表明，胶原蛋白 IX 已进化为原纤维间网络结合剂。遗传证据支持了这一点，即所有三种 IX 胶原蛋白基因的突变都可以产生以软骨基质完整性和早发性骨关节炎为特征的表型。根据软骨胶原杂聚物的结构，我们还预测端肽（非三螺旋）蛋白水解裂解在胶原原纤维的重塑和降解中的关键作用。
Research on cartilage is intensifying as efforts expand to discover disease-modifying drugs to treat or prevent osteoarthritis. Proteolytic damage to the collagen fabric of cartilage is a critical, and probably early, component of the pathogenesis of degenerative joint disease. Here we summarize recent findings on the unique heteromeric structure of cartilage collagen fibrils, including the key role of collagen IX, a covalently bonded fibril-adapter molecule. A highly specific pattern of cross-linking sites that involves all three component gene products strongly suggests that collagen IX has evolved to function as an interfibrillar network-bonding agent. This is supported from the genetic evidence that mutations in all three collagen IX genes can produce a phenotype in which cartilage matrix integrity and early-onset osteoarthritis are a feature. From the structure of the cartilage collagen heteropolymer we also predict a pivotal role for telopeptide (non-triple-helical) proteolytic cleavages in the remodelling and degradation of collagen fibrils.