Circ_0044235 regulates the development of osteoarthritis by the modulation of miR-375/PIK3R3 axis.

Background: Circular RNAs (circRNAs) play an important role in osteoarthritis (OA). However, the role of circRNA in OA is still unclear. Here, we explored the role and mechanism of circ_0044235 in OA.

Methods: CHON-001 cells were treated with IL-1β to establish OA model in vitro. The levels of circ_0044235, miR-375 and phosphoinositide 3-kinase (PI3K) regulatory subunit 3 (PIK3R3) were detected by quantitative real-time PCR. Cell count kit-8 assay and flow cytometry assay were used to detect cell viability and apoptosis. The concentrations of inflammation factors were determined by enzyme-linked immunosorbent assay. Western blot was used to detect protein levels. The interaction between miR-375 and circ_0044235 or PIK3R3 was analyzed by dual-luciferase reporter assay and RNA immunoprecipitation assay.

Results: Circ_0044235 was significantly decreased in OA cartilage tissue and IL-1β-treated CHON-001 cells. Overexpression of circ_0044235 promoted IL-1β-stimulated CHON-001 cell viability and inhibited apoptosis, inflammation, and extracellular matrix (ECM) degradation. In mechanism analysis, circ_0044235 could act as a sponge for miR-375 and positively regulate PIK3R3 expression. In addition, miR-375 ameliorated the effect of circ_0044235 overexpression on IL-1β-mediated CHON-001 cells injury. In addition, miR-375 inhibition mitigated IL-1β-induced CHON-001 cell injury, while PIK3R3 silencing restored the effect.

Conclusion: Circ_0044235 knockdown alleviated IL-1β-induced chondrocytes injury by regulating miR-375/PIK3R3 axis, confirming that circ_0044235 might be a potential target for OA treatment.