Circ_0001721 knockdown relieves IL-1β-induced chondrocyte injury via regulating miR-373-3p/CXCR4 in osteoarthritis.

BACKGROUND

Circular RNA (circRNA) plays an important role in osteoarthritis (OA) progression. Circ_0001721 has been noted to be significantly overexpressed in OA patients, but its function in OA progression remain unclear. The purpose of this study was to investigate the role and mechanism of circ_0001721 in OA progression.

METHODS

Interleukin-1β (IL-1β)-induced chondrocytes were used to mimic OA cell model in vitro. The expression of circ_0001721, microRNA (miR)-373-3p and CXC chemokine receptor 4 (CXCR4) was examined by quantitative real-time PCR. The concentrations of inflammatory factors were assessed by ELISA assay. Cell proliferation and apoptosis were determined by MTT assay, EdU assay and flow cytometry. Protein levels were detected by western blot analysis. The interaction between miR-373-3p and circ_0001721 or CXCR4 was confirmed by dual-luciferase reporter assay, RIP assay and RNA pull-down assay.

RESULTS

Our results showed that circ_0001721 was highly expressed in OA patients and IL-1β-induced chondrocytes. IL-1β treatment could suppress the proliferation, while promote the apoptosis, extracellular matrix (ECM) degradation and inflammation of chondrocytes. Knockdown of circ_0001721 alleviated IL-1β-induced chondrocyte injury. MiR-373-3p could be sponged by circ_0001721, and its inhibitor reversed the regulation of circ_0001721 knockdown on IL-1β-induced chondrocyte injury. CXCR4 was a target of miR-373-3p, and circ_0001721 could sponge miR-373-3p to regulate CXCR4. Furthermore, miR-373-3p overexpression inhibited IL-1β-induced chondrocyte injury, and these effects could be overturned by CXCR4 upregulation.

CONCLUSION

Our data confirmed that circ_0001721 knockdown alleviated IL-1β-induced chondrocyte injury by miR-373-3p/CXCR4 axis, which suggested that circ_0001721 might be a potential therapeutic target for OA.