SENP1 mitigates intervertebral disc degeneration: mechanisms involving suppression of pyroptosis and apoptosis in nucleus pulposus cells

BACKGROUND: Intervertebral disc degeneration (IDD) is a leading cause of global disability. This study aimed to systematically investigate the role of SUMOylation in the pathogenesis of IDD through integrated transcriptomic analysis. METHODS: Bioinformatics analysis was performed on public transcriptomic datasets (GEO). Human nucleus pulposus (NP) cells were used for experimental validation, followed by RNA sequencing and mechanistic studies. A rat IDD model was established to assess the effects of modulating SUMOylation in vivo. RESULTS: SUMOylation was found to be significantly involved in IDD. The expression of the deSUMOylating enzyme SENP1 was downregulated in degenerated NP cells. Overexpression of SENP1 alleviated cellular senescence and extracellular matrix metabolic dysfunction. Further mechanistic studies revealed that SENP1 exerted its protective effects by inhibiting both apoptosis and pyroptosis in NP cells. In the rat IDD model, intervention targeting SUMOylation markedly slowed disease progression. CONCLUSION: This study demonstrates that SENP1 attenuates IDD progression by suppressing apoptosis and pyroptosis, highlighting the central role of SUMOylation in IDD pathogenesis and identifying the SENP1 axis as a potential therapeutic target for this debilitating condition.