Circ_DHRS3 positively regulates GREM1 expression by competitively targeting miR-183-5p to modulate IL-1 beta-administered chondrocyte proliferation, apoptosis and ECM degradation

Background: Osteoarthritis (OA) is a chronic inflammatory disease caused by degenerative changes of articular cartilage, involving in the expression changes of special circular RNAs (circRNAs). This study aimed to explore the role of circ_DHRS3 in OA cell models and provide a potential mechanism. Methods: OA cell models were constructed using human chondrocytes with Interleukin-1 beta (IL-1 beta) treatment. The expression of circ_DHRS3, microRNA (miR)-183-5p and Gremlin 1 (GREM1) mRNA was detected using realtime quantitative polymerase chain reaction (RT-qPCR). Cell proliferation was identified using 3-[4, 5-dimethylthiazol-2-yl]-2, 5 diphenyl tetrazolium bromide (MTT) assay. Cell apoptosis was investigated using flow cytometry assay. The protein levels of proliferation- and apoptosis-related proteins were quantified by western blot. The levels of extracellular matrix (ECM)-associated proteins were quantified by western blot to assess ECM degradation. The relationship between miR-183-5p and circ_DHRS3 or GREM1 was predicted and then verified by dual-luciferase reporter assay. Results: Circ_DHRS3 expression was elevated in OA cartilage tissues and IL-1 beta-treated chondrocytes. Circ_DHRS3 was resistant to RNase R and Actinomycin D. Circ_DHRS3 knockdown promoted chondrocyte proliferation inhibited by IL-1 beta, and alleviated IL-1 beta-induced apoptosis and ECM degradation, which were reversed by the inhibition of miR-183-5p, a target of circ_DHRS3. MiR-183-5p restoration also enhanced IL-1 beta-blocked cell proliferation, and relieved IL-1 beta-induced cell apoptosis and ECM degradation, while GREM1 (a target of miR-Y183-5p) overexpression abolished the effects of miR-183-5p restoration. Moreover, circ_DHRS3 regulated GREM1 expression by targeting miR-183-5p. Conclusion: Circ_DHRS3 mediated IL-1 beta-administered chondrocyte proliferation, apoptosis and ECM degradation by positively regulating GREM1 expression via competitively targeting miR-183-5p.

Automated summary

In this study, elevated expression of circ_DHRS3 in OA cartilage tissues and IL-1 beta-treated chondrocytes was found. Circ_DHRS3 was shown to play a role in regulating chondrocyte proliferation, apoptosis, and ECM degradation through the miR-183-5p/GREM1 pathway. This research provides insights into the potential mechanisms of OA and suggests circ_DHRS3 as a potential therapeutic target.