Spermidine protects cartilage from IL-1β-mediated ferroptosis.

Rheumatoid arthritis is characterized by a burst of inflammation, the destruction of cartilage and the abundant release of inflammatory factors such as IL-1β. Thus, the effect of IL-1β on cartilage was examined in this study. IL-1β could cause lipid peroxidation and disturbances in iron metabolism by increasing the expression of NCOA4 and decreasing the expression of FTH, which also induced ferritinophagy. In addition, the expression of the key antioxidant proteins SLC7A11 and GPX4 was inhibited by IL-1β, resulting in ferroptosis in chondrocytes. Spermidine (SPD), a low-molecular-weight aliphatic nitrogen-containing compound that widely exists in animals, has been reported to be an antioxidant. In our study, we found that SPD could inhibit ferritinophagy and reverse the decrease in the expression of SLC7A11 and GPX4. Therefore, we uncovered one of the molecular mechanisms of cartilage destruction and inflammation and provide a potential polyamine for the treatment of RA.