Osteoarthritis (OA) is a chronic degenerative joint disease. Extracellular matrix (ECM) degradation is essential for OA progression. Previous studies have shown that circular RNAs (circRNAs) are involved in the pathological process of OA. CircPRKCH has been shown to be upregulated in OA chondrocytes. The present study was aimed to explore the roles of circPRKCH in vivo and in vitro models of OA and its underlying molecular mechanisms. IL-1β-induced chondrocytes and mice injected with monosodium iodoacetate were used as OA models in vitro and in vivo, respectively. RT-qPCR was performed to measure the expression of circPRKCH, miR-145, and HGF in cartilage tissues and chondrocytes. The interaction between miR-145 and circPRKCH or HGF was verified by a dual-luciferase reporter assay. Chondrocyte apoptosis, viability, and ECM-related proteins were examined by flow cytometry, MTT assay, and Western blotting, respectively. Histopathological changes were detected by HE and Safranin O-fast green staining. The expression of circPRKCH and HGF was increased in OA cartilage tissues and IL-1β-treated chondrocytes, while miR-145 expression was decreased. IL-1β induced chondrocyte apoptosis and ECM degradation in chondrocytes. Moreover, circPRKCH promoted HGF expression and activated HGF/c-MET by directly binding to miR-145. miR-145 knockdown or HGF overexpression significantly reversed circPRKCH knockdown-mediated inhibition of apoptosis and ECM degradation in IL-1β-induced chondrocytes. Besides, miR-145 overexpression alleviated IL-1β-induced chondrocyte apoptosis and ECM degradation by inhibiting HGF/c-MET. Finally, circPRKCH knockdown reduced ECM degradation by regulating the miR-145/HGF axis in an experimental OA model in mice. Our study demonstrated that circPRKCH promoted chondrocyte apoptosis and ECM degradation via the miR-145/HGF axis in OA, which may provide a novel target for OA treatment.

中文翻译：

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CircPRKCH 通过调节骨关节炎中的 miR-145/HGF 轴来调节细胞外基质的形成和代谢

骨关节炎（OA）是一种慢性退行性关节疾病。细胞外基质 (ECM) 降解对于 OA 进展至关重要。以往的研究表明环状RNA（circRNA）参与了OA的病理过程。已显示 CircPRKCH 在 OA 软骨细胞中上调。本研究旨在探讨circPRKCH在OA体内和体外模型中的作用及其潜在的分子机制。IL-1β诱导的软骨细胞和注射碘乙酸钠的小鼠分别用作体外和体内的OA模型。进行 RT-qPCR 以测量软骨组织和软骨细胞中 circPRKCH、miR-145 和 HGF 的表达。miR-145 与 circPRKCH 或 HGF 之间的相互作用通过双荧光素酶报告基因分析得到验证。软骨细胞凋亡，活力，分别通过流式细胞术、MTT 法和蛋白质印迹法检测 ECM 和 ECM 相关蛋白。HE和番红O-fast绿色染色检测组织病理学变化。OA 软骨组织和 IL-1β 处理的软骨细胞中 circPRKCH 和 HGF 的表达增加，而 miR-145 的表达降低。IL-1β 在软骨细胞中诱导软骨细胞凋亡和 ECM 降解。此外，circPRKCH 通过直接结合 miR-145 促进 HGF 表达并激活 HGF/c-MET。miR-145 敲低或 HGF 过表达显着逆转了 circPRKCH 敲低介导的 IL-1β 诱导的软骨细胞凋亡和 ECM 降解的抑制作用。此外，miR-145 过表达通过抑制 HGF/c-MET 来减轻 IL-1β 诱导的软骨细胞凋亡和 ECM 降解。最后，circPRKCH 敲低通过在小鼠实验性 OA 模型中调节 miR-145/HGF 轴来减少 ECM 降解。我们的研究表明，circPRKCH 在 OA 中通过 miR-145/HGF 轴促进软骨细胞凋亡和 ECM 降解，这可能为 OA 治疗提供新的靶点。