Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu, China.
Department of Orthopedics, Yixing People's Hospital, Yixing 214200, Jiangsu, China.
J Immunol Res. 2023 Jun 30;2023:2061071. doi: 10.1155/2023/2061071. eCollection 2023.
Dysregulation of miRNAs in chondrocytes has been confirmed to participate in osteoarthritis (OA) progression. Previous study has screen out several key miRNAs may play crucial role in OA based on bioinformatic analysis. Herein, we identified the downregulation of miR-1 in OA samples and inflamed chondrocytes. The further experiments revealed that miR-1 played an essential role in maintaining chondrocytes proliferation, migration, antiapoptosis, and anabolism. Connexin 43 (CX43) was further predicted and confirmed to be the target of miR-1, and mediated the promotion effects of miR-1 in regulating chondrocyte functions. Mechanistically, miR-1 maintained the expression of GPX4 and SLC7A11 by targeting CX43, attenuated the accumulation of intracellular ROS, lipid ROS, MDA, and Fe in chondrocytes, thereby inhibiting the ferroptosis of chondrocytes. Finally, experimental OA model was constructed by anterior cruciate ligament transection surgery, and Agomir-1 was injected into the joint cavity of mice to assess the protective effect of miR-1 in OA progression. Histological staining, immunofluorescence staining and Osteoarthritis Research Society International score revealed that miR-1 could alleviate the OA progression. Therefore, our study elucidated the mechanism of miR-1 in OA in detail and provided a new insight for the treatment of OA.
软骨细胞中 miRNAs 的失调已被证实参与骨关节炎（OA）的进展。先前的研究基于生物信息学分析筛选出了几种可能在 OA 中发挥关键作用的关键 miRNAs。在此，我们发现 miR-1 在 OA 样本和炎症性软骨细胞中下调。进一步的实验表明，miR-1 在维持软骨细胞增殖、迁移、抗凋亡和合成代谢方面发挥着重要作用。间隙连接蛋白 43（CX43）进一步被预测和证实是 miR-1 的靶标，并介导了 miR-1 调节软骨细胞功能的促进作用。机制上，miR-1 通过靶向 CX43 维持 GPX4 和 SLC7A11 的表达，减弱了软骨细胞内 ROS、脂质 ROS、MDA 和 Fe 的积累，从而抑制了软骨细胞的铁死亡。最后，通过前交叉韧带切断术构建实验性 OA 模型，并向小鼠关节腔注射 Agomir-1 来评估 miR-1 在 OA 进展中的保护作用。组织学染色、免疫荧光染色和骨关节炎研究协会国际评分显示，miR-1 可减轻 OA 的进展。因此，我们的研究详细阐明了 miR-1 在 OA 中的作用机制，并为 OA 的治疗提供了新的思路。
