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.

译文

骨关节炎 (OA) 是一种慢性且普遍的退行性肌肉骨骼疾病,其特征是关节软骨退化和关节炎症。MicroRNA-203a (miR-203a) 已被证明参与OA期间的多个病理过程,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对关节软骨退化和关节炎症的影响。我们观察到,在OA组织和OA的体外模型中,miR-203a水平分别显着上调。抑制miR-203a可显著减轻白细胞介素 (IL)-1β 诱导的软骨细胞炎症反应和ECM降解。此外,抗去胸截瘫同源物3 (Smad3) 是维持软骨细胞稳态的关键因素,被确定为软骨细胞miR-203a的推定靶标。更重要的是,Smad3的抑制损害了miR-203a对il-1β 诱导的炎症反应和ECM降解的抑制作用。总的来说,这些结果表明,miR-203a可能通过靶向Smad3来促进OA的关节软骨降解,从而为OA的治疗提供了新的治疗靶标。

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