Abstract

Background:Nucleus pulposus (NP) cell apoptosis and extracellular matrix (ECM) degradation constitute the two major pathological hallmarks of intervertebral disc degeneration (IVDD). Inhibiting these deleterious processes represents an effective strategy for attenuating IVDD progression. Sirtuin 7 (SIRT7), a member of the sirtuin family, plays a critical role in modulating gene expression, mediating cellular stress adaptation, and facilitating DNA repair. While SIRT7 has demonstrated therapeutic potential across diverse pathological contexts, its specific contribution to IVDD pathogenesis remains elusive. This study aimed to delineate the functional contribution of SIRT7 to IVDD progression and unravel its molecular mechanisms.Methods:We quantified SIRT7 levels by immunohistochemistry (IHC) in degenerative human and rat NP tissues, and by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in tert-butyl hydroperoxide (TBHP)-treated NP cells. To evaluate the protective capacity of SIRT7 overexpression, we conducted multifaceted analyses encompassing oxidative stress markers, apoptotic indices, ECM turnover, and nuclear factor kappa B (NF-κB) cascade activity in TBHP-challenged NP cells, utilizing reactive oxygen species detection probes, mitochondrial membrane potential indicators, Hoechst 33342 nuclear staining, qRT-PCR, western blotting, and immunofluorescence techniques. Its therapeutic potential was subsequently validated through magnetic resonance imaging and comprehensive histopathological evaluation (hematoxylin and eosin, Safranin O/Fast Green, and Masson trichrome staining) combined with IHC in a rat IVDD puncture model.Results:SIRT7 was consistently downregulated in degenerated human and rat NP tissues as well as TBHP-treated NP cells, concomitant with elevated NF-κB pathway activation. SIRT7 overexpression in TBHP-stimulated NP cells effectively attenuated oxidative stress, apoptosis, and ECM degradation. Mechanistically, SIRT7 overexpr