CircRSU1 contributes to the development of osteoarthritis via the miR-345-3p/TRAF6 signaling

Objective: Osteoarthritis (OA) is a common type of prevalent joint diseases in the elderly. At present, circular RNAs receive more attention due to their roles during the progression of OA. In this paper, the expression profiles of circRSU1 and relevant molecules in OA patients and cell models were evaluated, and the underlying regulatory mechanisms of circRSU1-modulated OA development were also explored. Methods: The proliferation of chondrocytes was examined using CCK-8 assay. The levels of relevant proteins were evaluated by western blotting. The production of pro-inflammatory cytokines were measured by ELISA. Results: The results revealed upregulation of circRSU1 in OA samples, and IL-1β treatment could elevate the expression of circRSU1 in human chondrocytes. In addition, knockdown of circRSU1 abolished the dysfunctions caused by IL-1β in chondrocytes. Furthermore, miR-345–3p was identified as the novel downstream molecule of circRSU1. The levels of miR-345–3p were notably decreased in cells transfected with oe-circRSU1 and elevated in cells treated with si-circRSU1, respectively. Moreover, si-circRSU1 was able to attenuate IL-1β-induced impairments in chondrocyte via miR-345–3p. In addition, to verify the downstream mechanisms of circRSU1-modulated OA progression, TRAF6 was identified as the putative target of miR-345–3p, and miR-345–3p inhibition abolished circRSU1 knockdown-triggered downregulation of TRAF6 in IL-1β-induced OA cell model. In addition, miR-345–3p protected chondrocytes from IL-1β-induced dysfunction such as impaired ECM, reduced proliferation and upregulated apoptosis of chondrocytes, and elevated production of proinflammatory cytokines through regulating TRAF6. Conclusion: In summary, circRSU1 was able to contribute to the progression of OA through regulating the miR-345–3p/TRAF6 pathway, and this novel signalling could be novel candidate for targeted therapy for OA patients.