Santamaria Salvatore
Centre for Haematology, London, UK.
Int J Exp Pathol. 2020 Feb;101(1-2):4-20. doi: 10.1111/iep.12344. Epub 2020 Mar 27.
A Disintegrin And Metalloproteinase with ThromboSpondin motif (ADAMTS)-5 was identified in 1999 as one of the enzymes responsible for cleaving aggrecan, the major proteoglycan in articular cartilage. Studies in vitro, ex vivo and in vivo have validated ADAMTS-5 as a target in osteoarthritis (OA), a disease characterized by extensive degradation of aggrecan. For this reason, it attracted the interest of many research groups aiming to develop a therapeutic treatment for OA patients. However, ADAMTS-5 proteoglycanase activity is not only involved in the dysregulated aggrecan proteolysis, which occurs in OA, but also in the physiological turnover of other related proteoglycans. In particular, versican, a major ADAMTS-5 substrate, plays an important structural role in heart and blood vessels and its proteolytic processing by ADAMTS-5 must be tightly regulated. On the occasion of the 20th anniversary of the discovery of ADAMTS-5, this review looks at the evidence for its detrimental role in OA, as well as its physiological turnover of cardiovascular proteoglycans. Moreover, the other potential functions of this enzyme are highlighted. Finally, challenges and emerging trends in ADAMTS-5 research are discussed.
1999年，一种具有血小板反应蛋白基序的解聚素和金属蛋白酶（ADAMTS）-5被确定为负责切割聚集蛋白聚糖（关节软骨中的主要蛋白聚糖）的酶之一。体外、离体和体内研究均已证实ADAMTS-5是骨关节炎（OA）的一个治疗靶点，OA是一种以聚集蛋白聚糖广泛降解为特征的疾病。因此，它引起了许多旨在为OA患者开发治疗方法的研究小组的关注。然而，ADAMTS-5蛋白聚糖酶活性不仅参与OA中发生的聚集蛋白聚糖蛋白水解失调，还参与其他相关蛋白聚糖的生理周转。特别是，多功能蛋白聚糖是ADAMTS-5的主要底物，在心脏和血管中发挥重要的结构作用，其由ADAMTS-5进行的蛋白水解过程必须受到严格调控。在ADAMTS-5发现20周年之际，本综述探讨了其在OA中有害作用的证据，以及其在心血管蛋白聚糖生理周转方面的作用。此外，还强调了该酶的其他潜在功能。最后，讨论了ADAMTS-5研究中的挑战和新趋势。
