骨关节炎中的 ADAMTS 和 ADAM 金属蛋白酶——超越“通常的嫌疑人”,Osteoarthritis and Cartilage

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骨关节炎中的 ADAMTS 和 ADAM 金属蛋白酶——超越“通常的嫌疑人”
Osteoarthritis and Cartilage ( IF 7.2 ) Pub Date : 2017-07-01 , DOI: 10.1016/j.joca.2017.02.791
C-Y Yang ₁ , A Chanalaris ₁ , L Troeberg ₁

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总结介绍基质金属蛋白酶 (MMP) 和“聚集蛋白聚糖酶”是一种解聚素和具有血小板反应蛋白基序的金属蛋白酶 (ADAMTS)，它们通过降解细胞外基质 (ECM) II 型胶原蛋白和蛋白聚糖在骨关节炎 (OA) 中发挥关键作用，因此OA 治疗的潜在目标。目的本文旨在全面综述其他鲜为人知的 ADAMTS 和相关的阿达马溶素（或解整合素和金属蛋白酶 (ADAM)）在软骨中的表达和潜在作用，以期确定软骨中潜在的保护性或稳态金属蛋白酶。联合和通知随后的选择性抑制剂设计。设计使用 PubMed 术语“骨关节炎”和“ADAMTS”或“ADAM”进行了全面的文献检索。结果几种ADAMTS和ADAM被鉴定为据报道在OA中表达增加。这些包括可能在软骨基质合成代谢中发挥作用的酶（例如前胶原 N-蛋白酶 ADAMTS-2、ADAMTS-3 和 ADAMTS-14）、软骨细胞分化和增殖（例如 ADAM9、ADAM10、ADAM12），以及酶促进软骨分解代谢（例如，软骨寡聚蛋白 (COMP) 降解 ADAMTS-7 和 ADAMTS-12）。结论除了充分表征的 MMP、ADAMTS-4 和 ADAMTS-5，许多其他 ADAMTS 和 ADAM 在软骨中表达，并且一些在 OA 中显示出显着改变的表达。

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ADAMTS and ADAM metalloproteinases in osteoarthritis – looking beyond the ‘usual suspects’

Summary Introduction Matrix metalloproteinases (MMPs) and ‘aggrecanase’ a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs) are well established to play key roles in osteoarthritis (OA) through degradation of extracellular matrix (ECM) type II collagen and aggrecan, and are thus potential targets for development of OA therapies. Objective This paper aims to provide a comprehensive review of the expression and potential roles of other, lesser-known ADAMTSs and related adamalysins (or a disintegrin and metalloproteinases (ADAMs)) in cartilage, with a view to identifying potentially protective or homeostatic metalloproteinases in the joint and informing consequent selective inhibitor design. Design A comprehensive literature search was performed using PubMed terms ‘osteoarthritis’ and ‘ADAMTS’ or ‘ADAM’. Results Several ADAMTSs and ADAMs were identified as having reportedly increased expression in OA. These include enzymes likely to play roles in cartilage matrix anabolism (e.g., the procollagen N-proteinases ADAMTS-2, ADAMTS-3 and ADAMTS-14), chondrocyte differentiation and proliferation (e.g., ADAM9, ADAM10, ADAM12), as well as enzymes contributing to cartilage catabolism (e.g., Cartilage oligomeric protein (COMP)-degrading ADAMTS-7 and ADAMTS-12). Conclusions In addition to the well-characterised MMPs, ADAMTS-4 and ADAMTS-5, many other ADAMTSs and ADAMs are expressed in cartilage and several show significantly altered expression in OA. Studies aimed at elucidating the pathophysiological roles of these enzymes in cartilage will contribute to our understanding of OA pathogenesis and enable design of targeted inhibitors that effectively target metalloproteinase-mediated cartilage degradation while sparing cartilage repair pathways.

更新日期：2017-07-01

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