Circ_0004662 promotes lipopolysaccharide-induced osteoarthritis by targeting the miR-450b-5p/TCF4 axis

Osteoarthritis (OA) is a multifactorial degenerative joint disease. Emerging evidence suggests that dysregulation of circular RNAs (circRNAs) may contribute to OA pathogenesis. In this study, we aimed to investigate the potential role and underlying mechanisms of circ_0004662 in chondrocyte dysfunction under inflammatory conditions.

Gene expression was silenced or overexpressed in chondrocytes by cell transfection. Bioinformatics analysis, dual-luciferase reporter assays, and RNA pull-down experiments were employed to validate the interaction within the circ_0004662/miR-450b-5p/TCF4 axis. Cell viability, apoptosis, expression of apoptosis-related proteins, and levels of inflammatory cytokines were assessed using CCK-8, flow cytometry, western blotting, and ELISA, respectively.

We found that circ_0004662 was significantly upregulated in OA cartilage tissues and in lipopolysaccharide (LPS)-stimulated chondrocytes. Functionally, knockdown of circ_0004662 attenuated LPS-induced chondrocyte injury, as evidenced by improved cell viability, increased anti-apoptotic protein expression, reduced apoptosis rate, decreased pro-apoptotic protein levels, and lower secretion of inflammatory cytokines. Mechanistically, circ_0004662 acted as a sponge for miR-450b-5p, thereby upregulating TCF4 expression.

Our findings suggest that circ_0004662 exacerbates inflammatory chondrocyte injury through the miR-450b-5p/TCF4 axis. These results highlight its potential involvement in OA-related inflammation. Key Points • circ_0004662 was obviously upregulated in OA. • circ_0004662 regulated LPS-induced OA chondrocyte injury by miR-450b-5p/TCF4. • circ_0004662/miR-450b-5p/TCF4 was valuable for the diagnosis of OA diagnosis.