Nardosinone suppresses monoiodoacetate-induced osteoarthritis in rats: The key role of the miR-218-5p/NUMB axis.

Nardosinone is a bioactive compound with a sesquiterpenoid structure isolated from Nardostachys jatamansi. The compound has shown treatment effects against skeletal disorders. In the current study, the effects of nardosinone on osteoarthritis (OA) were first assessed and the mechanism underlying the effects was explored by detecting changes in the miR-218-5p/NUMB axis. The miR, as a potential target mediating the effects of nardosinone on OA, was first determined with microarray and RT-qPCR detections. Then, OA symptoms were induced in rats using monoiodoacetate (MIA) and treated with nardosinone. The anti-OA effects of nardosinone were assessed via the detection of the histological structure and inflammation. The role of miR-218-5p was delineated by modulating its levels in OA-affected rats. Based on the results of microarray and RT-qPCR detections, miR-218-5p was selected as the therapeutic target for nardosinone. The induction of OA resulted in tissue destruction and the production of cytokines in rat joint tissues, which was associated with the up-regulation of miR-218-5p and the downregulation of NUMB. For OA-affected rats treated with nardosinone, the joint structure was improved and the inflammatory response was suppressed, along with the restored expression levels of miR-218-5p and NUMB. The re-induced level of miR-218-5p compromised the anti-OA effects of nardosinone, indicating that the inhibition of the miR played an indispensable role in the anti-OA function of nardosinone. Collectively, the findings of our study demonstrated that nardosinone exerts treatment effects against OA by modulating the miR-218-5p/NUMB axis. Future studies will provide more detailed information on the interaction between nardosinone and miR in the attenuation of OA.