Zmpste24 deficiency contributes to intervertebral disc degeneration by undermining the stability of the nuclear membrane of nucleus pulposus cells.

Intervertebral disc degeneration (IVDD) is often accompanied by the senescence of nucleus pulposus (NP) cells and narrowed intervertebral disc space. Zinc metalloproteinase STE24 (Zmpste24), a common anti-aging gene, has been studied in several diseases but remains understudied in IVDD. This study aimed to investigate the relationship between IVDD and alterations in Zmpste24 expression. Immunohistochemical staining revealed that reduced Zmpste24 expression in patients with IVDD. In vitro experiments using rat NP cells revealed that Zmpste24 inhibition induced nuclear instability and cellular senescence. In addition, the phenotype and immunohistochemical staining of Zmpste24 knockout (KO) mice confirmed that Zmpste24 plays a protective role against IVDD. Collectively, these findings suggest that reduced Zmpste24 expression in NP cells may contribute to IVDD pathogenesis.