Dysregulation of the NUDT7-PGAM1 axis is responsible for chondrocyte death during osteoarthritis pathogenesis

Osteoarthritis (OA) is the most common degenerative joint disease; however, its etiopathogenesis is not completely understood. Here we show a role forNUDT7in OA pathogenesis. Knockdown ofNUDT7in normal human chondrocytes results in the disruption of lipid homeostasis. Moreover,Nudt7−/−mice display significant accumulation of lipids via peroxisomal dysfunction, upregulation ofIL-1βexpression, and stimulation of apoptotic death of chondrocytes. Our genome-wide analysis reveals thatNUDT7knockout affects the glycolytic pathway, and we identifyPgam1as a significantly altered gene. Consistent with the results obtained on the suppression ofNUDT7, overexpression ofPGAM1in chondrocytes induces the accumulation of lipids, upregulation ofIL-1βexpression, and apoptotic cell death. Furthermore, these negative actions ofPGAM1in maintaining cartilage homeostasis are reversed by the co-introduction ofNUDT7. Our results suggest thatNUDT7could be a potential therapeutic target for controlling cartilage-degrading disorders.