Circ_0001103 alleviates IL-1β-induced chondrocyte cell injuries by upregulating SIRT1 via targeting miR-375

Background: Osteoarthritis (OA) is a common inflammatory disease characterized by articular cartilage degeneration and injury. Circular RNAs (circRNAs) are widely involved in the development of human diseases, including OA. The objective of this study was to investigate the function and functional mechanism of circ_0001103 in OA. Methods: Cell model of OA was established by treating chondrocytes with interleukin-1 beta (IL-1 beta). The expression of circ_0001103, miR-375 and sirtuin 1 (SIRT1) mRNA was measured using quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability was assessed using cell counting kit-8 (CCK-8) assay. Cell apoptosis was determined using flow cytometry assay. The expression levels of inflammatory factors were quantified by qRT-PCR. The expression of extracellular matrix (ECM) metabolism-related markers, including Collagen Type II Alpha 1 Chain (COL2A1) and A disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4), was detected by western blot. Predicted target relationship between miR-375 and circ_0001103 or SIRT1 by the bioinformatics tools was validated by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Results: Circ_0001103 was downregulated in OA tissues and IL-1 beta-induced chondrocytes. Overexpression of circ_0001103 attenuated IL-1 beta-induced chondrocyte apoptosis, inflammatory responses and ECM degradation. MiR-375 was targeted by circ_0001103, and miR-375 could bind to SIRT1. Circ_0001103 overexpression increased the expression of SIRT1 by suppressing miR-375. Rescue experiments suggested that miR-375 restoration reversed the effects of circ_0001103 overexpression, and SIRT1 knockdown overturned the effects of miR-375 inhibition. Conclusion: Circ_0001103 governed the miR-375/SIRT1 axis to ameliorate IL-1 beta-induced chondrocyte injuries, implying that circ_0001103 was a promising biomarker in OA pathogenesis.

Automated summary

The study revealed that circ_0001103 alleviated IL-1 beta-induced chondrocyte injuries by regulating the miR-375/SIRT1 axis, suggesting circ_0001103 as a potential promising biomarker in the pathogenesis of OA.