Osteoarthritis (OA) is one of the most common degenerative joint diseases worldwide. Chondrocytes are activated in OA patients, accompanied by excessive chondrogenic proliferation and production of inflammatory cytokines. MiR-467b is implicated in the regulation of artherosclerosis and pro-inflammatory cytokine secretion. However, the precise role of miR-467b in OA remains unclear. In the present study, we induced inflammation in chondrogenic ATDC5 cells using lipopolysaccharide (LPS). LPS treatment significantly elevated the production of interleukin-6 (IL-6), IL-1β and tumour necrosis factor-α (TNF-α) in ATDC5 cells, accompanied by decreased miR-467 level. Then, we over-expressed miR-467b using its specific mimics in ATDC5 cells, and LPS-induced inflammation was significantly inhibited as evidenced by decreased IL-6, IL-1β and TNF-α levels. MiR-467b agomir also alleviated inflammation in rat knee osteoarthritis (KOA) model. In addition, we validated that signal transducer and activator of transcription 1 (STAT1) was a downstream target of miR-467b. LPS treatment significantly increased the STAT1 expression while miR-467b mimic transfection partially reversed this effect. Moreover, STAT1 knockout reversed the increased contents of IL-6, IL-1β and TNF-α. Furthermore, miR-467b over-expression significantly decreased the production of IL-6, IL-1β and TNF-α induced by LPS treatment, which was partially reversed by further STAT1 over-expression. In summary, our findings demonstrated that miR-467b alleviated LPS-induced inflammation through targeting STAT1, and this miR-467b/STAT1 regulation axis may provide a new therapeutic target for OA clinical management.

中文翻译：

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MiR-467b 通过靶向软骨形成 ATDC5 细胞中的 STAT1 减轻脂多糖诱导的炎症

骨关节炎（OA）是全球最常见的退行性关节疾病之一。OA 患者的软骨细胞被激活，伴随着过度的软骨增生和炎性细胞因子的产生。MiR-467b 与动脉粥样硬化和促炎细胞因子分泌的调节有关。然而，miR-467b 在 OA 中的确切作用仍不清楚。在本研究中，我们使用脂多糖 (LPS) 在软骨形成 ATDC5 细胞中诱导炎症。LPS 治疗显着提高了 ATDC5 细胞中白细胞介素 6 (IL-6)、IL-1β 和肿瘤坏死因子-α (TNF-α) 的产生，同时 miR-467 水平降低。然后，我们在 ATDC5 细胞中使用其特异性模拟物过度表达 miR-467b，并且 LPS 诱导的炎症得到显着抑制，这可以通过 IL-6、IL-1β 和 TNF-α 水平降低来证明。MiR-467b agomir 还减轻了大鼠膝骨关节炎 (KOA) 模型中的炎症。此外，我们验证了信号转导和转录激活因子 1 (STAT1) 是 miR-467b 的下游靶标。LPS 处理显着增加了 STAT1 表达，而 miR-467b 模拟转染部分逆转了这种效应。此外，STAT1 敲除逆转了 IL-6、IL-1β 和 TNF-α 含量的增加。此外，miR-467b 过表达显着降低了 LPS 处理诱导的 IL-6、IL-1β 和 TNF-α 的产生，这被进一步的 STAT1 过表达部分逆转。总之，我们的研究结果表明，miR-467b 通过靶向 STAT1 减轻 LPS 诱导的炎症，这种 miR-467b/STAT1 调节轴可能为 OA 临床管理提供新的治疗靶点。