Department of Orthopedics, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
Department of Orthopedics, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
Int Immunopharmacol. 2022 Sep;110:109029. doi: 10.1016/j.intimp.2022.109029. Epub 2022 Jul 20.
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.
软骨细胞凋亡和功能障碍在骨关节炎（OA）中起着重要作用，OA 是一种慢性进行性关节病。非编码 RNA 与 OA 的发病机制有关。在这项研究中，发现 microRNA（miR）-548d-5p 在 OA 样本和 IL-1β刺激的软骨细胞中表达下调。miR-548d-5p 的过表达部分逆转了体外 IL-1β诱导的软骨细胞损伤，表现在促进细胞生长、抑制细胞凋亡和炎性细胞因子释放以及改善细胞外基质（ECM）沉积。此外，miR-548d-5p 的过表达部分逆转了木瓜蛋白酶诱导的 OA 大鼠膝关节软骨损伤。特异性蛋白 1（SP1）被 miR-548d-5p 抑制，并被鉴定为其直接下游靶标。在 IL-1β刺激的软骨细胞中，SP1 的过表达显著减弱了 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 样本和 IL-1β刺激的软骨细胞中异常下调。miR-548d-5p 通过直接抑制 SP1 来保护软骨细胞免受 IL-1β诱导的损伤。
