Emerging evidence suggests that dysregulated circular RNAs (circRNAs) play a pivotal role in osteoarthritis (OA). Circ_0045714 is a functional circRNAs, and has been revealed to involve in the process of OA. However, the molecular mechanisms by which circ_0045714 regulates OA progression are not thoroughly elucidated. Circ_0045714 expression was decreased in OA and TNF-α-induced chondrocytes, ectopic overexpression of circ_0045714 abolished TNF-α-induced cell apoptosis, inflammation, extracellular matrix (ECM) degradation promotion and proliferation inhibition. In a mechanical study, circ_0045714 targeted miR-218-5p, and miR-218-5p overexpression reversed the effects of circ_0045714 on TNF-α-induced chondrocytes. Besides that, HRAS was a target of miR-218-5p, and HRAS knockdown attenuated the protective effects of miR-218-5p inhibition on TNF-α-induced chondrocyte dysfunction. Additionally, circ_0045714 could regulate HRAS expression via miR-218-5p in chondrocytes. Up-regulation of circ_0045714 suppressed TNF-α-induced chondrocyte growth inhibition, inflammation, and ECM degradation via miR-218-5p/HRAS axis, suggesting a novel insight into the pathogenesis of OA and the potential protective role of circ_0045714 in the occurrence and development of OA.

新出现的证据表明，失调的环状 RNA（circRNA）在骨关节炎（OA）中起着关键作用。Circ_0045714 是一种功能性 circRNA，已被揭示参与 OA 过程。然而，circ_0045714 调节 OA 进展的分子机制尚未完全阐明。Circ_0045714 在 OA 和 TNF-α 诱导的软骨细胞中表达降低，circ_0045714 的异位过表达消除了 TNF-α 诱导的细胞凋亡、炎症、细胞外基质 (ECM) 降解促进和增殖抑制。在一项机械研究中，circ_0045714 靶向 miR-218-5p，miR-218-5p 过表达逆转了 circ_0045714 对 TNF-α 诱导的软骨细胞的影响。除此之外，HRAS 是 miR-218-5p 的靶点，和 HRAS 敲低减弱了 miR-218-5p 抑制对 TNF-α 诱导的软骨细胞功能障碍的保护作用。此外，circ_0045714 可以通过 miR-218-5p 在软骨细胞中调节 HRAS 表达。circ_0045714 的上调通过 miR-218-5p/HRAS 轴抑制 TNF-α 诱导的软骨细胞生长抑制、炎症和 ECM 降解，表明对 OA 发病机制的新见解和 circ_0045714 在发生和发生的潜在保护作用OA的发展