Curcumin inhibits chondrocyte apoptosis and inflammation in osteoarthritis via the miR-338-3p/EIF4A1 signaling axis.

Abstract

OBJECTIVE: Osteoarthritis (OA) is a degenerative joint disorder mainly characterized by articular cartilage degradation. Curcumin, the primary bioactive compound derived from turmeric, exhibits anti-inflammatory, antioxidant, and anti-catabolic activities. This study aimed to explore the therapeutic potential of curcumin in OA and its underlying mechanism involving the microRNA-338-3p (miR-338-3p)/Eukaryotic Translation Initiation Factor 4A1 (EIF4A1) signaling pathway. METHODS: Mouse models of OA were established, including groups treated with curcumin or intra-articular injection of miR-338-3p agomir, along with an in vitro chondrocyte model. Modulation of miR-338-3p and EIF4A1 expression was achieved through siRNA interference. Gene expression was quantified via quantitative real-time polymerase chain reaction and Western blot; the targeting interaction between miR-338-3p and EIF4A1 was confirmed using a luciferase reporter assay; and cellular viability and inflammatory mediator levels were evaluated with Cell Counting Kit-8, flow cytometry, and enzyme-linked immunosorbent assay. Cartilage tissue pathology was also examined. RESULTS: EIF4A1 was markedly upregulated in OA cartilage, whereas miR-338-3p targeted and suppressed EIF4A1 expression. Curcumin administration elevated miR-338-3p levels and reduced EIF4A1 expression. Moreover, curcumin, miR-338-3p overexpression, and EIF4A1 knockdown attenuated chondrocyte apoptosis, enhanced proliferation, and modulated apoptosis-related protein expression (decreasing cleaved caspase-3 and Bax, increasing Bcl-2). Curcumin also suppressed the secretion of inflammatory cytokines (IL-6, TNF-α, IL-1β, etc.), decreased synthesis of matrix-degrading enzymes (Matrix Metalloproteinase-13 (MMP13), A Disintegrin and Metalloproteinase with Thrombospondin Motifs (ADAMTS)), and reduced OARSI scores, ultimately ameliorating OA progression. CONCLUSION: These results demonstrate that curcumin mitigates chondrocyte apoptosis, attenuates cartilage inflammation, and downregulates joint matrix-degrading enzyme expression in OA through the miR-338-3p/EIF4A1 axis, suggesting this pathway as a promising target for gene therapy in OA.