Competitive endogenous RNAs (ceRNAs), as a newly identified regulating mechanism, have been demonstrated to play a crucial role in various human diseases. An increasing number of recent studies have revealed that circular RNAs (circRNAs) can function as ceRNAs. However, little is known about the role of circFAM160A2 in the pathological process of osteoarthritis (OA). This study is the first to examine the crucial role of the circFAM160A2-miR-505-3p-SIRT3 axis in osteoarthritis progression. miR-505-3p was selected from the interaction of a microRNA (miRNA) microarray comparing chondrocytes in OA and normal conditions and prediction results from TargetScan. RT-qPCR was performed to assess the expression of circFAM160A2, miR-505-3p, and SIRT3. A dual luciferase assay was used to validate the binding of circFAM160A2, miR-505-3p, and SIRT3. We used lentivirus and adeno-associated virus to establish in vitro and in vivo overexpression models. Western blotting, apoptosis assay, ROS detection assay, Safranin O staining, and CCK-8 assay were employed to assess the role of circFAM160A2, miR-505-3p, and SIRT3. We found that miR-505-3p was upregulated and circFAM160A2 was downregulated in OA. While overexpression of circFAM160A2 decreased the production of extracellular matrix (ECM) degrading enzymes and ameliorated chondrocyte apoptosis and mitochondrial dysfunction, inhibition of miR-505-3p could reverse the protective effect of circFAM160A2 on the OA phenotype both in vitro and in vivo. In conclusion, circFAM160A2 can promote mitochondrial stabilization and apoptosis reduction in OA chondrocytes by targeting miR-505-3p and SIRT3, which might be a potential therapeutic target for OA therapy.

中文翻译：

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circFAM160A2 通过靶向 miR-505-3p 和 SIRT3 促进骨关节炎软骨细胞的线粒体稳定和凋亡减少

竞争性内源性RNA（ceRNA）作为一种新发现的调节机制，已被证明在各种人类疾病中发挥着至关重要的作用。最近越来越多的研究表明，环状 RNA (circRNA) 可以作为 ceRNA 发挥作用。然而，关于circFAM160A2在骨关节炎（OA）病理过程中的作用知之甚少。这项研究首次检验了 circFAM160A2-miR-505-3p-SIRT3 轴在骨关节炎进展中的关键作用。miR-505-3p 选自 microRNA (miRNA) 微阵列的相互作用，比较了 OA 和正常条件下的软骨细胞以及来自 TargetScan 的预测结果。进行 RT-qPCR 以评估 circFAM160A2、miR-505-3p 和 SIRT3 的表达。双荧光素酶测定用于验证 circFAM160A2、miR-505-3p 和 SIRT3 的结合。我们使用慢病毒和腺相关病毒建立体外和体内过表达模型。采用蛋白质印迹、细胞凋亡测定、ROS 检测测定、番红 O 染色和 CCK-8 测定来评估 circFAM160A2、miR-505-3p 和 SIRT3 的作用。我们发现 miR-505-3p 在 OA 中上调，而 circFAM160A2 下调。虽然 circFAM160A2 的过表达降低了细胞外基质 (ECM) 降解酶的产生并改善了软骨细胞凋亡和线粒体功能障碍，但抑制 miR-505-3p 可以逆转 circFAM160A2 在体外和体内对 OA 表型的保护作用。总之，circFAM160A2 可以通过靶向 miR-505-3p 和 SIRT3 促进 OA 软骨细胞的线粒体稳定和凋亡减少，