GNF-5837 alleviates intervertebral disc ageing by upregulating glutathione peroxidase 7

OBJECTIVE: The aim of this study was to investigate the role of glutathione peroxidase 7 (GPX7) in mitigating oxidative stress-induced cellular ageing and its contribution to intervertebral disc degeneration (IVDD). INTRODUCTION: Human nucleus pulposus (NP) cells in degenerated intervertebral discs (IVDs) show signs of ageing, such as telomere shortening, DNA damage, and mitochondrial dysfunction. GPX7, known for its ability to protect against ageing in cancer cells, may also play a role in NP cell ageing. METHODS: Two datasets (GSE34095 and GSE147383) were analysed to compare GPX7 expression in normal and degenerated IVDs and used KEGG analysis to identify related pathways. An H₂O₂-induced cell model and a natural ageing model were used to simulate ageing. GPX7 was transfected into and overexpressed in NP cells, and its protective effects were examined. Molecular docking identified GNF-5837 as a potential compound to prevent GPX7 cleavage, which was tested in an IVDD rat model. RESULTS: The expression of GPX7 was increased in degenerated IVDs and H₂O₂-induced models. GPX7 overexpression reduced ageing in NP cells. GNF-5837 alleviated IVDD in rats by upregulating GPX7. CONCLUSION: Our study demonstrates that GNF-5837 reduced the expression of ageing markers by upregulating GPX7, suggesting it could serve as a potential treatment for IVDD.