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

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.