CircPRKCH modulates extracellular matrix formation and metabolism by regulating the miR-145/HGF axis in osteoarthritis

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13075-022-02893-9.