Xu Lin, Li Yefu
Department of Developmental Biology, Harvard School of Dental Medicine, 188 Longwood Ave. Boston, MA 02115 & Faculty of Medicine, Harvard Medical School 25 Shattuck St. Boston, MA 02115, United States.
Curr Drug Targets. 2020;21(9):838-848. doi: 10.2174/1389450121666200214121323.
Preserving of articular cartilage is an effective way to protect synovial joints from becoming osteoarthritic (OA) joints. Understanding of the molecular basis of articular cartilage degeneration will provide valuable information in the effort to develop cartilage preserving drugs. There are currently no disease-modifying OA drugs (DMOADs) available to prevent articular cartilage destruction during the development of OA. Current drug treatments for OA focus on the reduction of joint pain, swelling, and inflammation at advanced stages of the disease. However, based on discoveries from several independent research laboratories and our laboratory in the past 15 to 20 years, we believe that we have a functional molecular understanding of articular cartilage degeneration. In this review article, we present and discuss experimental evidence to demonstrate a sequential chain of the molecular events underlying articular cartilage degeneration, which consists of transforming growth factor beta 1, high-temperature requirement A1 (a serine protease), discoidin domain receptor 2 (a cell surface receptor tyrosine kinase for native fibrillar collagens), and matrix metalloproteinase 13 (an extracellularmatrix degrading enzyme). If, as we strongly suspect, this molecular pathway is responsible for the initiation and acceleration of articular cartilage degeneration, which eventually leads to progressive joint failure, then these molecules may be ideal therapeutic targets for the development of DMOADs.
保留关节软骨是保护滑膜关节不发展为骨关节炎（OA）关节的有效方法。了解关节软骨退变的分子基础将为开发保护软骨的药物提供有价值的信息。目前尚无疾病修饰性OA药物（DMOADs）可用于预防OA发展过程中的关节软骨破坏。目前针对OA的药物治疗主要集中在疾病晚期减轻关节疼痛、肿胀和炎症。然而，基于过去15至20年几个独立研究实验室以及我们实验室的发现，我们相信我们对关节软骨退变有了功能性的分子认识。在这篇综述文章中，我们展示并讨论实验证据，以证明关节软骨退变背后分子事件的连续链条，该链条由转化生长因子β1、高温需求A1（一种丝氨酸蛋白酶）、盘状结构域受体2（一种针对天然纤维状胶原蛋白的细胞表面受体酪氨酸激酶）和基质金属蛋白酶13（一种细胞外基质降解酶）组成。如果正如我们强烈怀疑的那样，这条分子途径负责关节软骨退变的起始和加速，最终导致进行性关节功能衰竭，那么这些分子可能是开发DMOADs的理想治疗靶点。
