Zhang Yuanmin, Wang Guodong, Ma Longfei, Wang Chengqun, Wang Lina, Guo Yanxia, Zhao Xiaowei
Department of Orthopedics, Affiliated Hospital of Jining Medical University Jining 272029, Shandong, China.
Department of Orthopedics, The Second Hospital of Shandong University Jinan 250000, Shandong, China.
Am J Transl Res. 2019 Nov 15;11(11):7027-7034. eCollection 2019.
Osteoarthritis (OA) is the most common degenerative joint disease. microRNAs (miRNAs) have been showen to act critical roles in several diseases including OA. However, the involvement and underlying mechanism of miR-137 in development of OA remains unkown. In our study, we firstly showed that IL-1β decreased the expression of miR-137 in the chondrocytes and we demonstrated that the miR-37 expression level was lower in the OA cases than in the control patients. Dual-luciferase reporter analysis was performed to confirm that ADAMTS-5 was a direct target gene of miR-137. Furthermore, we indicated that elevated expression of miR-137 decreased the protein expression of ADAMTS-5 in the chondrocytes. In additional, we showed that IL-1β induces the ADAMTS-5 expression in the chondrocytes. The ADAMTS-5 expression level was higher in the OA cases than in the control patients. We showed that the expression of ADAMTS-5 was negatively correlated with the miR-137 expression level in OA tissues. Overexpression of miR-137 suppressed cell growth, extracellular matrix (ECM) degradation and inflammation in chondrocytes. These preliminary data elucidated that miR-137 suppressed OA progression via inhibiting cell growth, inflammation and ECM degradation.
骨关节炎(OA)是最常见的退行性关节疾病。微小RNA(miRNA)已被证明在包括OA在内的多种疾病中发挥关键作用。然而,miR-137在OA发生发展中的作用及潜在机制仍不清楚。在我们的研究中,我们首先发现白细胞介素-1β(IL-1β)降低了软骨细胞中miR-137的表达,并且我们证明OA患者中miR-137的表达水平低于对照患者。进行双荧光素酶报告基因分析以证实含血小板反应蛋白基的解聚素样金属蛋白酶5(ADAMTS-5)是miR-137的直接靶基因。此外,我们指出miR-137表达升高会降低软骨细胞中ADAMTS-5的蛋白表达。另外,我们发现IL-1β可诱导软骨细胞中ADAMTS-5的表达。OA患者中ADAMTS-5的表达水平高于对照患者。我们发现OA组织中ADAMTS-5的表达与miR-137的表达水平呈负相关。miR-137的过表达抑制了软骨细胞的生长、细胞外基质(ECM)降解和炎症。这些初步数据表明,miR-137通过抑制细胞生长、炎症和ECM降解来抑制OA的进展。