Bisphenol A disrupts cartilage homeostasis through dual targeting of TP53 and PTGS2 signaling networks

Background Bisphenol A (BPA), a ubiquitous endocrine-disrupting chemical (EDC), disrupts hormonal signaling and induces inflammation, yet its role in osteoarthritis (OA) pathogenesis remains unclear, underscoring a critical environmental health research gap. Methods We employed network toxicology and molecular docking techniques to analyze BPA’s interactions with OA-associated protein targets. Key genes were identified through multi-database integration and prioritized using topological metrics (degree/betweenness/closeness centrality). Enrichment analysis (GO/KEGG) was conducted to map biological pathways, while molecular docking simulations (CB-Dock2) evaluated binding affinities between BPA and core targets. Results Integrated analysis identified 233 shared BPA-OA targets. Enrichment revealed BPA disrupted ECM organization (p = 3.2×10⁻⁵), activated NF-κB/MAPK pathways (p < 0.001), and altered arachidonic acid metabolism. Molecular docking showed high-affinity BPA binding to TP53 (− 8.0 kcal/mol), CYP2C19 (− 8.1 kcal/mol), and PTGS2 (− 7.7 kcal/mol). Key targets were dysregulated: TP53 (↑2.3-fold in chondrocytes) and PTGS2 (↑4.5-fold PGE₂). Conclusion This study provides a new theoretical framework for understanding the mechanism of action of BPA in OA, emphasizing the role of network toxicology in exacerbating OA. These findings may inform future research on the risk of exposure to DEP and provide important insights for public health policy and the development of targeted therapeutic strategies.