Osthole Improves Rat Arthritis Through the miR-34a/Bcl-2 Axis

Knee osteoarthritis (KOA), also referred to as hypertrophic or degenerative arthritis, is a prevalent joint disorder. Current clinical management strategies include pharmacological therapy, physical intervention, surgical procedures, and adjunctive treatments. While these approaches can alleviate KOA symptoms to some extent, they often come with limitations, such as side effects, limited efficacy, or invasiveness. Osthole (OST), a natural coumarin derivative, has been widely studied for its medicinal properties, particularly in alleviating joint pain and improving articular function. In this study, CCK8 assay, transmission electron microscopy (TEM), H&E staining, and serum biochemical analysis were employed to demonstrate that OST exerts protective effects on chondrocytes both in vitro and in vivo, with no significant toxicity observed. Subsequent investigations using TEM, acridine orange staining, flow cytometry, and western blotting revealed that OST promotes autophagy and suppresses apoptosis in chondrocytes. Further mechanistic studies through qRT-PCR and luciferase reporter assays indicated that OST downregulates miR-34a, thereby upregulating Bcl-2 expression and inhibiting apoptosis via the miR-34a/Bcl-2 pathway. In summary, these findings indicate that OST protects chondrocytes in both cellular and animal models, attenuating LPS-induced stress and reducing inflammation and apoptosis in KOA rats. The downregulation of miR-34a and subsequent increase in Bcl-2 expression contribute to its anti-apoptotic effect. These results provide a theoretical foundation for the development of OST-based patented drugs and their potential clinical translation in KOA therapy.