Osteoarthritis (OA) is a very common chronic and degenerative joint disease characterized by persistent destruction of articular cartilage. Recently, increasing evidence showed that circular RNAs (circRNAs) play critical roles in OA progression. However, the functions of circRNAs in OA and their underlying mechanisms of action remain unclear. In the present study, the expression levels of circRNA-UBE2G1 and HIF-1a were significantly increased in OA tissues, whereas miR‑373 expression was downregulated. Function assays showed that circRNA-UBE2G1 inhibition reduced the effects of LPS on C28/I2 cells viability and apoptosis. In terms of mechanism, we revealed that circRNA-UBE2G1 binds to miR‑373 as competing endogenous RNAs (ceRNAs). HIF-1a might act as a target of miR‑373. Moreover, miR‑373 suppression or HIF-1a overexpression restored the effects of circRNA-UBE2G1 downregulation on LPS-induced chondrocytes injury. Collectively, our data suggest that circRNA-UBE2G1 facilitates the progression in the LPS-induced OA cell model via regulating the miR‑373/HIF-1a axis.

Abbreviations

OA: Osteoarthritis; Circular RNAs; miRNAs: MicroRNAs; Mut: Mutant; WT: Wild type; UTR: Untranslated region.

中文翻译：

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circRNA-UBE2G1 通过 miR-373/HIF-1a 轴调节 LPS 诱导的骨关节炎。

骨关节炎（OA）是一种非常常见的慢性退行性关节疾病，其特征是关节软骨的持续破坏。最近，越来越多的证据表明环状 RNA（circRNA）在 OA 进展中起着关键作用。然而，circRNAs在OA中的功能及其潜在的作用机制仍不清楚。在本研究中，circRNA-UBE2G1和HIF-1a在OA组织中的表达水平显着增加，而miR-373的表达水平下调。功能测定表明，circRNA-UBE2G1 抑制降低了 LPS 对 C28/I2 细胞活力和凋亡的影响。在机制方面，我们发现circRNA-UBE2G1作为竞争性内源RNA（ceRNA）与miR-373结合。HIF-1a 可能作为 miR-373 的靶标。而且，miR-373 抑制或 HIF-1a 过表达恢复了 circRNA-UBE2G1 下调对 LPS 诱导的软骨细胞损伤的影响。总的来说，我们的数据表明circRNA-UBE2G1通过调节miR-373/HIF-1a轴促进LPS诱导的OA细胞模型的进展。

缩写

OA：骨关节炎；环状RNA；miRNA：微小RNA；Mut：突变体；WT：野生型；UTR：未翻译区域。