Abstract：
Chondrocyte apoptosis and dysfunction play an important role in osteoarthritis (OA), a chronic progressive arthropathy. Non-coding RNAs have been implicated in OA pathogenesis. In this study, microRNA (miR)-548d-5p was found to be downregulated in OA samples and IL-1β-stimulated chondrocytes. miR-548d-5p overexpression partially reversed IL-1β-induced chondrocyte damage in vitro, evidenced by the promotion of cell growth, the inhibition of apoptosis and inflammatory cytokine release, and the improvement in extracellular matrix (ECM) deposition. Furthermore, miR-548d-5p overexpression partially reversed papain-induced damages on OA rat\'s knee articular cartilage. Specificity protein 1 (SP1) was inhibited by miR-548d-5p and identified as its direct downstream target. In IL-1β-stimulated chondrocytes, SP1 overexpression significantly attenuated the protective effects of miR-548d-5p overexpression against chondrocyte damage. In conclusion, miR-548d-5p was abnormally downregulated in OA samples and IL-1β-stimulated chondrocytes. miR-548d-5p protects against IL-1β-induced chondrocyte damage via direct inhibition of SP1.
摘要：
软骨细胞凋亡和功能障碍在骨关节炎(OA)慢性进行性关节病.非编码RNA与OA发病机理有关。在这项研究中,发现microRNA(miR)-548d-5p在OA样品和IL-1β刺激的软骨细胞中下调。miR-548d-5p过表达部分逆转IL-1β诱导的软骨细胞损伤,细胞生长的促进证明，抑制细胞凋亡和炎症细胞因子的释放，和改善细胞外基质（ECM）沉积。此外，miR-548d-5p过表达可部分逆转木瓜蛋白酶诱导的OA大鼠膝关节软骨损伤.特异性蛋白1（SP1）被miR-548d-5p抑制，并被确定为其直接下游靶标。在IL-1β刺激的软骨细胞中，SP1过表达显著减弱miR-548d-5p过表达对软骨细胞损伤的保护作用。总之,miR-548d-5p在OA样品和IL-1β刺激的软骨细胞中异常下调。miR-548d-5p通过直接抑制SP1保护IL-1β诱导的软骨细胞损伤。
