The dysregulated circular RNAs (circRNAs) are relevant to the development of osteoarthritis (OA). The circRNA serpin family E member 2 (circSERPINE2) is dysregulated in OA, while the role and mechanism of circSERPINE2 in OA are largely unknown. The aim of our research is to explore how and whether circSERPINE2 regulates interleukin-1β (IL-1β)-caused chondrocyte damage in OA. In present study, the chondrocytes (CHON-001 cells) were exposed to IL-1β to mimic the injury in OA. CircSERPINE2, microRNA-495 (miR-495) and transforming growth factor-β receptor 2 (TGFBR2) abundances were detected via quantitative reverse transcription polymerase chain reaction or western blot. Cell apoptosis was assessed via viability, apoptotic rate and caspase-3 activity. Extracellular matrix was investigated by levels of Sry-type high-mobility-group box 9 (SOX9), collagen type II alpha 1 (COL2A1) and Aggrecan using western blot. The interaction among circSERPINE2, miR-495 and TGFBR2 was assessed via dual-luciferase reporter analysis and RNA immunoprecipitation. The results showed that circSERPINE2 expression was reduced in OA patients and IL-1β-treated chondrocytes. CircSERPINE2 overexpression mitigated IL-1β-caused apoptosis and extracellular matrix degradation. miR-495 was targeted by circSERPINE2 and up-regulated in OA patients and IL-1β-treated chondrocytes. miR-495 up-regulation reversed overexpression of circSERPINE2-mediated inhibition of apoptosis and extracellular matrix degradation. TGFBR2 was targeted by miR-495 and lowly expressed in OA patients and IL-1β-treated chondrocytes. CircSERPINE2 could mediate TGFBR2 expression by binding with miR-495. As a conclusion, CircSERPINE2 attenuated IL-1β-caused apoptosis and extracellular matrix degradation of chondrocytes by regulating miR-495/TGFBR2 axis, indicating a new target for OA treatment.

中文翻译：

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CircSERPINE2通过调节miR-495 / TGFBR2轴来减弱IL-1β引起的软骨细胞凋亡和软骨细胞外基质降解。

环状RNA（circRNA）失调与骨关节炎（OA）的发展有关。circRNA serpin家族E成员2（circSERPINE2）在OA中失调，而circSERPINE2在OA中的作用和机制尚不清楚。我们的研究目的是探讨circSERPINE2如何以及是否调节OA中由白介素1β（IL-1β）引起的软骨细胞损伤。在本研究中，软骨细胞（CHON-001细胞）暴露于IL-1β以模拟OA中的损伤。通过定量逆转录聚合酶链反应或蛋白质印迹检测到CircSERPINE2，microRNA-495（miR-495）和转化生长因子-β受体2（TG​​FBR2）的丰度。通过存活力，凋亡率和caspase-3活性评估细胞凋亡。通过Sry型高迁移率族框9（SOX9）的水平研究细胞外基质，使用Western印迹检测II型胶原蛋白α1（COL2A1）和Aggrecan。circSERPINE2，miR-495和TGFBR2之间的相互作用是通过双重荧光素酶报告基因分析和RNA免疫沉淀来评估的。结果表明，在OA患者和经IL-1β治疗的软骨细胞中，circSERPINE2表达降低。CircSERPINE2过表达减轻了IL-1β引起的细胞凋亡和细胞外基质降解。miR-495被circSERPINE2靶向，并在OA患者和IL-1β治疗的软骨细胞中被上调。miR-495上调逆转了circSERPINE2介导的凋亡抑制和细胞外基质降解的过度表达。TGFBR2被miR-495靶向，在OA患者和IL-1β治疗的软骨细胞中低表达。CircSERPINE2可以通过与miR-495结合来介导TGFBR2表达。作为结论，