Department of Orthopedics II, The First Affiliated Hospital of Xinxiang Medical University, Weihui 453100, Henan, China.
Department of Orthopedics IV, The First Affiliated Hospital of Xinxiang Medical University, Weihui 453100, Henan, China.
Biosci Rep. 2020 Mar 27;40(3). doi: 10.1042/BSR20192723.
Osteoarthritis (OA) is a chronic and prevalent degenerative musculoskeletal disorder, which is characterized by articular cartilage degradation and joint inflammation. MicroRNA-203a (miR-203a) has been shown to be involved in multiple pathological processes during OA, but little is known about its function in chondrocyte extracellular matrix (ECM) degradation. In the present study, we aimed to elucidate the effects of miR-203a on articular cartilage degradation and joint inflammation. We observed that the miR-203a level was significantly up-regulated in OA tissues and in an in vitro model of OA, respectively. Inhibition of miR-203a significantly alleviated the interleukin (IL)-1β-induced inflammatory response and ECM degradation in chondrocytes. Moreover, mothers against decapentaplegic homolog 3 (Smad3), a key factor in maintaining chondrocyte homeostasis, was identified as a putative target of miR-203a in chondrocytes. More importantly, inhibition of Smad3 impaired the inhibitory effects of the miR-203a on IL-1β-induced inflammatory response and ECM degradation. Collectively, these results demonstrated that miR-203a may contribute to articular cartilage degradation of OA by targeting Smad3, suggesting a novel therapeutic target for the treatment of OA.
骨关节炎（OA）是一种慢性和普遍存在的退行性肌肉骨骼疾病，其特征是关节软骨降解和炎症。已经表明 microRNA-203a（miR-203a）参与 OA 过程中的多种病理过程，但对其在软骨细胞细胞外基质（ECM）降解中的功能知之甚少。在本研究中，我们旨在阐明 miR-203a 对关节软骨降解和关节炎症的影响。我们观察到，miR-203a 的水平在 OA 组织和 OA 的体外模型中分别显著上调。miR-203a 的抑制显著减轻了软骨细胞中白细胞介素（IL）-1β诱导的炎症反应和 ECM 降解。此外，母系抗德尔塔蛋白 3（Smad3），一种维持软骨细胞稳态的关键因素，被鉴定为软骨细胞中 miR-203a 的一个假定靶点。更重要的是，抑制 Smad3 损害了 miR-203a 对 IL-1β 诱导的炎症反应和 ECM 降解的抑制作用。总之，这些结果表明，miR-203a 可能通过靶向 Smad3 导致 OA 关节软骨降解，为 OA 的治疗提供了一个新的治疗靶点。
