Li Chao, Cao Yong Ping, Guan Zhen Peng, Huang De Yong, Ge Zi Gang
Department of Biomedical Engineering, Peking University College of Engineering, Beijing 100871, China.
Beijing Da Xue Xue Bao Yi Xue Ban. 2009 Oct 18;41(5):611-2.
Osteoarthritis is mainly caused by the degenerative changes of cartilage and cartilage extracellular matrix, while Aggrecanases degradate Proteoglycans which are the major components of cartilage. This review includes three aspects: (1) We have concluded the major enzymes(ADAMTS-4 and ADAMTS-5) which regulate the metabolism of cartilage extracellular matrix. Meanwhile, we have summarized the structure of aggrecanases(ADAMTS-4 and ADAMTS-5) and introduced the function of each regional structure; (2) We have concluded the way cytokines and glycosaminoglycans regulate the metabolism of aggrecanases, and discussed the regulation and control principle of cytokines and glycosaminoglycan; (3) We have summarized the majority of inhibitors to the aggrecanases, introduced the endogenic inhibitors, and put our emphasis on the extrinsic inhibitors (chelating agents, polypeptides and so on). Through deeper research on the enzymes, it will help us further understand the pathogenesis of osteoarthritis, and open up new avenues to clinical treatment.
骨关节炎主要由软骨及软骨细胞外基质的退行性改变引起,而聚集蛋白聚糖酶可降解作为软骨主要成分的蛋白聚糖。本综述涵盖三个方面:(1)我们总结了调节软骨细胞外基质代谢的主要酶(ADAMTS - 4和ADAMTS - 5)。同时,我们概述了聚集蛋白聚糖酶(ADAMTS - 4和ADAMTS - 5)的结构,并介绍了各区域结构的功能;(2)我们总结了细胞因子和糖胺聚糖调节聚集蛋白聚糖酶代谢的方式,并讨论了细胞因子和糖胺聚糖的调控原理;(3)我们总结了大多数针对聚集蛋白聚糖酶的抑制剂,介绍了内源性抑制剂,并重点阐述了外源性抑制剂(螯合剂、多肽等)。通过对这些酶的深入研究,将有助于我们进一步了解骨关节炎的发病机制,并为临床治疗开辟新途径。