CircRNA-UBE2G1 regulates LPS-induced osteoarthritis through miR-373/HIF-1a axis

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

骨关节炎（Osteoarthritis, OA）是一类极为常见的慢性退行性关节疾病，以关节软骨持续性破坏为核心病理特征。近年来，越来越多研究证据表明环状RNA（circular RNAs, circRNAs）在骨关节炎的病程进展中发挥关键调控作用。然而，环状RNA在骨关节炎中的具体功能及其潜在作用机制仍未阐明。本研究检测发现，骨关节炎组织中circRNA-UBE2G1与缺氧诱导因子-1α（HIF-1α）的表达水平显著升高，而微小RNA-373（miR-373）的表达则呈下调趋势。功能实验结果显示，抑制circRNA-UBE2G1可减轻脂多糖（lipopolysaccharide, LPS）对C28/I2细胞活力与凋亡的影响。在分子机制层面，本研究揭示circRNA-UBE2G1可作为内源竞争RNA（competing endogenous RNAs, ceRNAs）结合miR-373；而HIF-1α或可作为miR-373的靶基因。此外，抑制miR-373或过表达HIF-1α可逆转circRNA-UBE2G1下调对脂多糖诱导的软骨细胞损伤所产生的保护效应。综上，本研究数据表明，circRNA-UBE2G1可通过调控miR-373/HIF-1α信号轴，促进脂多糖诱导的骨关节炎细胞模型的病程进展。注：OA：骨关节炎；circRNAs：环状RNA；miRNAs：微小RNA；Mut：突变体；WT：野生型；UTR：非翻译区。