Spermine Alleviates Chondrocyte Senescence and Extracellular Matrix Degradation by Suppressing NF-κB Signaling, with Odc1 Acting as a Potential Upstream Regulator

Osteoarthritis (OA) is a prevalent degenerative joint disease with no disease-modifying therapy currently available. Spermine (SPM), a natural polyamine, shows therapeutic potential, but its role and mechanism in OA remain unclear. In this study, SPM expression was examined in OA cartilage, and the effects of exogenous SPM on chondrocyte senescence and extracellular matrix degradation were assessed in vitro and in a rat OA model. Bioinformatics analysis and Odc1 knockdown experiments were performed to identify the upstream regulator of SPM. The results showed that SPM was significantly downregulated in TBHP-stimulated chondrocytes. Exogenous SPM supplementation alleviated chondrocyte senescence, inhibited matrix degradation, and attenuated cartilage degeneration in vivo. Mechanistically, SPM inhibited NF-κB signaling, and Odc1 was identified as a key upstream regulator of SPM. In conclusion, SPM alleviates chondrocyte senescence and matrix degradation in vitro and attenuates OA progression in vivo. These effects are partially achieved by suppressing NF-κB signaling and upregulating Odc1, indicating that SPM is a promising therapeutic candidate for OA.