BQU57 suppresses IL-1β-induced apoptosis and extracellular matrix degradation in nucleus pulposus cells by blocking the NF-κB signaling pathway

Background: Intervertebral disc degeneration (IVDD) is a significant contributor to lower back pain (LBP), affecting approximately 80 % of the global population. The RalA inhibitor BQU57 plays a role in various cellular functions; however, its impact on nucleus pulposus cell (NPC) degeneration remains unclear.

Methods: This study employed a combination of bioinformatics analysis and experimental validation to investigate the role of RALA in IVDD and its inhibitor BQU57 in its therapeutic potential. Gene expression datasets from the GEO database were analyzed to identify genes associated with IVDD, and clinical intervertebral disc samples were collected to validate the upregulation of RALA in degenerated discs. In vivo and in vitro assessments were conducted to evaluate the effects of BQU57 on the extracellular matrix (ECM) metabolism and Apoptosis of nucleus pulposus (NP) cells.

Results: Elevated expression of RALA was observed in degenerated intervertebral discs from IVDD patients, and its expression was correlated with disease severity. Further mechanistic studies revealed that the RALA inhibitor BQU57 could balance ECM metabolism and Apoptosis, potentially through the activation of the NF-κB signaling pathway.

Conclusion: RALA plays a significant role in the pathogenesis of IVDD, and it may serve as a novel therapeutic target for IVDD. BQU57 demonstrates potential as an effective small molecule drug for the prevention and treatment of IVDD.

Apoptosis; BQU57; Inflammation; Intervertebral disc degeneration; NF-κB signaling pathways.