DBC1 promotes intervertebral disc degeneration by activating NF-κB pathway and inhibiting SIRT1 activity

Aims: Intervertebral disc degeneration (IVDD) is a leading contributor to spinal degenerative diseases; however, its pathogenesis remains only partially elucidated. Recent studies have highlighted that the diminished activity of SIRT1 and the aberrant activation of the NF-kappa B signaling pathway are critical pathogenic factors in IVDD. DBC1 has been identified as a regulator of SIRT1 activity and the NF-kappa B signaling pathway. This study aimed to investigate the role of DBC1 in IVDD. Materials and methods: The expression levels of DBC1 in the nucleus pulposus of aging rats were quantified. Both overexpression and knockdown of DBC1 were utilized to explore their effects on the extracellular matrix (ECM) of the nucleus pulposus. Furthermore, the influence of DBC1 on cellular senescence, apoptosis, and ECM regulation in nucleus pulposus cells was assessed using Western blot (WB), cellular fluorescence assays, and histological staining techniques. Key findings: Our results demonstrate that DBC1 expression is significantly upregulated in IVDD. Moreover, DBC1 appears to contribute to IVDD by promoting apoptosis, senescence, and ECM degradation in nucleus pulposus cells. Mechanistic investigations revealed that DBC1 activates the NF-kappa B signaling pathway while suppressing SIRT1 expression in nucleus pulposus cells, suggesting that these two mechanisms underlie its effects on IVDD. Significance: In summary, this study provides evidence that DBC1 may play a pivotal role in the pathogenesis of IVDD by inhibiting SIRT1 activity and activating the NF-kappa B signaling pathway. Consequently, targeting DBC1 suppression could represent a promising therapeutic strategy for managing IVDD.