Naringin Mitigates Chondrocyte Apoptosis in Osteoarthritis by Suppressing the miR-29a-3p-Bax Pathway

Abstract

The present study aims to explore potential therapeutic effects of Naringin on osteoarthritis (OA) and investigate the underlying mechanism. The chondrocytes in the joint usually undergo detrimental changes during OA progression, including increased apoptosis. miRNAs emerge as crucial regulators in this processes. The study delves into the intricate interplay between miR-29a-3p, BAX-mediated apoptosis, and Naringin intervention. Pro-inflammatory cytokines induce chondrocyte apoptosis in OA, impacting cell viability. Naringin treatment effectively restores cell survivability (1.8-fold change), inhibiting caspase activity (0.54-fold change) and lowering matrix metalloproteinases-9 (MMP-9) (0.50-fold change) and MMP-13 expression (0.50-fold change). Furthermore, COL2A1, Sox9, Runx2, TGF-β1, and BMP-4 levels in cytokines-stimulated chondrocytes were enhanced by Naringin, accompanied by decreased productions of MMP3 and MMP13. In cartilage tissues of OA rats, Osteoarthritis Research Society International (OARSI) scores in Safranin O staining were elevated, Pro-inflammatory cytokine productions and MMP3 and MMP13 expressions were enhanced, and COL2A1, Sox9, Runx2, TGF-β1, and BMP-4 levels were reduced, which were remarkably rescued by Naringin. We further revealed the intricate connection between miR-29a-3p and the chondrocyte fate. Elevated miR-29a-3p expression corresponds to increased apoptotic chondrocytes. Naringin suppresses miR-29a-3p, curbing apoptosis and suggesting a potential therapeutic avenue. Notably, BAX emerges as a key player, with miR-29a-3p influencing its expression. Naringin's mitigation of BAX upregulation underscores its protective role. Overall, we found the potential role of Naringin in addressing chondrocyte apoptosis in OA through miR-29a-3p-BAX modulation, offering insights into innovative OA management strategies.