Proteolysis of the collagen fibril in osteoarthritis
Proteolysis of the collagen fibril in osteoarthritis
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DOI：
10.1042/bss0700115
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发表时间：
2003-01-01
期刊：
影响因子：
--
通讯作者：
Billinghurst, RC
中科院分区：
文献类型：
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作者：
Poole, AR;Nelson, F;Billinghurst, RC
骨关节炎软骨病理的发展涉及对胶原纤维网络的过度损伤，这似乎主要由软骨细胞产生的细胞因子白介素-1和肿瘤坏死因子(x)以及胶原酶基质金属蛋白酶-1 （MMP-1）和MMP-13介导。这些和其他MMPs对基质造成的损伤可导致产生足够的降解产物，这些降解产物本身可引起进一步降解，导致软骨细胞分化，最终导致基质矿化和细胞死亡。了解这些MMPs、细胞受体和细胞因子通路，以及通过选择性阻断功能选择性拮抗它们的能力，可能为骨关节炎和其他涉及软骨吸收的关节疾病（如类风湿关节炎）的治疗提供宝贵的治疗机会。检测这些降解事件释放到患者体液中的产物的能力可能使我们能够监测疾病活动，预测疾病进展并更快地确定新治疗剂的疗效。
The development of cartilage pathology in osteoarthritis involves excessive damage to the collagen fibrillar network, which appears to be mediated primarily by the chondrocyte-generated cytokines interleukin-1 and tumour necrosis factor (x and the collagenases matrix metalloproteinase-1 (MMP-1) and MMP-13. The damage to matrix caused by these and other MMPs can result in the production of sufficient degradation products that can themselves elicit further degradation, leading to chondrocyte differentiation and eventually matrix mineralization and cell death. Knowledge of these MMPs, cellular receptors and cytokine pathways, and the ability to selectively antagonize them by selective blockade of function, may provide valuable therapeutic opportunities in the treatment of osteoarthritis and other Joint diseases involving cartilage resorption, such as rheumatoid arthritis. The ability to detect the products of these degradative events released into body fluids of patients may enable us to monitor disease activity, predict disease progression and determine more rapidly the efficacy of new therapeutic agents.