Recent studies have demonstrated that microRNAs (miRNAs) are involved in many pathological conditions including osteoarthritis (OA). In this study, we aimed to investigate the role of miR-197 in OA and the potential molecular mechanism. The expression levels of miR-197 was detected by quantitative real-time PCR analysis. Cell proliferation and migration abilities were performed by MTT and transwell assays. The concentrations of inflammatory cytokines, including IL-1β, IL-6, and TNF-α, were detect using ELISA assay. Furthermore, luciferase reporter and rescue assays were applied to identify the functional target gene of miR-197 in OA. The results showed that miR-197 expression was significantly downregulated in the OA cartilage tissues compared with normal cartilage tissues, accompanied by upregulation of EIF4G2 expression. An inverse correlation was found between EIF4G2 and miR-197 expressions in OA cartilage tissues. Treatment with miR-197 mimics promoted the growth and migration abilities of chondrocytes, while miR-197 inhibitors induced the opposite effects. Furthermore, restoration of miR-197 significantly decreased IL-1β, IL-6, and TNF-α expression, whereas knockdown of miR-197 led to a induction in these inflammatory mediators. Moreover, EIF4G2 was predicted and confirmed as a directly target of miR-197. Overexpressed miR-197 could downregulate EIF4G2 expression in chondrocytes, while miR-197 knockdown could elevate EIF4G2 expression. Additionally, EIF4G2 overexpression reversed the effects of miR-197 mimics on chondrocytes proliferation, migration and inflammation. Taken together, our study demonstrated that miR-197 promotes chondrocyte proliferation, increases migration, and inhibits inflammation in the pathogenesis of OA by targeting EIF4G2, indicating the potential therapeutic targets of the miR-197/EIF4G2 axis for OA treatment.

中文翻译：

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MicroRNA-197通过靶向EIF4G2来调节骨关节炎发病机理中的软骨细胞增殖，迁移和炎症。

最近的研究表明，microRNA（miRNA）与许多病理状况有关，包括骨关节炎（OA）。在这项研究中，我们旨在研究miR-197在OA中的作用以及潜在的分子机制。通过定量实时PCR分析检测miR-197的表达水平。细胞增殖和迁移能力通过MTT和transwell测定法进行。用ELISA法检测包括IL-1β，IL-6和TNF-α在内的炎性细胞因子的浓度。此外，荧光素酶报告基因和拯救试验被应用于鉴定OA中miR-197的功能靶基因。结果显示，与正常软骨组织相比，OA软骨组织中miR-197表达显着下调，并伴随EIF4G2表达上调。在OA软骨组织中发现EIF4G2和miR-197表达之间呈负相关。miR-197模拟物的治疗促进了软骨细胞的生长和迁移能力，而miR-197抑制剂诱导了相反的作用。此外，miR-197的恢复显着降低了IL-1β，IL-6和TNF-α的表达，而miR-197的敲低导致这些炎症介质的诱导。此外，EIF4G2被预测并确认为miR-197的直接靶标。过度表达的miR-197可能下调软骨细胞中EIF4G2的表达，而miR-197的降低可能会提高EIF4G2的表达。另外，EIF4G2过表达逆转了miR-197模拟物对软骨细胞增殖，迁移和炎症的作用。两者合计，我们的研究表明miR-197促进软骨细胞增殖，