Bisphenol a exposure induces low back pain associated with intervertebral disc degeneration via BIRC3-mediated nucleus pulposus cell senescence.

OBJECTIVE

This study aimed to assess the correlation of bisphenol A (BPA) exposure with low back pain (LBP) and determine if the underlying molecular mechanism involved accelerating intervertebral disc degeneration (IDD).

METHODS

The National Health and Nutrition Examination Survey 2009-2010 data (n = 1163) were subjected to weighted logistic regression and restricted cubic spline analyses to link urinary BPA with LBP. A 127-algorithm machine learning framework identified core targets, which were validated using single-cell RNA sequencing (scRNA-seq) and molecular dynamics analyses. Finally, in vitro experiments were performed to verify whether BPA regulates nucleus pulposus cells (NPCs) via the predicted core targets.

RESULTS

Epidemiological analysis revealed that urinary BPA concentrations were significantly and positively correlated with LBP risk. In the adjusted model, participants in the highest quartile exhibited an increased risk of LBP (odds ratio = 3.35; P < 0.01). Machine learning and molecular simulations identified BIRC3 as the core target (Shapely Additive Explanations value = 0.127; binding energy: -6.3 kcal/mol). scRNA-seq analysis revealed that BIRC3 was specifically enriched in the regulatory NPC subpopulation of IDD tissues. In vitro experiments confirmed that BPA activated the BIRC3/p53 pathway, promoting NPC senescence, upregulating inflammatory and pain-related factors, and downregulating type II collagen.

CONCLUSION

This study demonstrated that BPA exposure is a potential risk factor for LBP and identified the BPA-IDD-LBP axis. BPA exposure activated the core mediator BIRC3 to induce NPC senescence and pain-related factor secretion. Targeting BIRC3 is a potential therapeutic strategy for IDD and LBP.