Investigating the mechanisms by which bisphenol A affects osteoarthritis through a novel network toxicology framework and experimental validation

BACKGROUND: In this study, we adopted network toxicology approaches to explore the potential risk effects of bisphenol A (BPA) on osteoarthritis (OA) processes. METHODS: Targets related to BPA were obtained from the ChEMBL, Swiss Target Prediction, and STITCH databases, and OA-related targets were obtained from the GeneCards, DisGeNET, and OMIM databases; using the obtained information, we identified common targets. Then, the core targets were determined using the STRING database and the Cytoscape software, and functional enrichment analysis was subsequently conducted to elucidate the potential mechanisms. Moreover, a comprehensive validation of the core targets was conducted through molecular docking and dynamics simulations. Moreover, clinical samples were collected for experimental validation. RESULTS: A total of 88 overlapping targets were identified, and six core targets (SRC, ESR1, EGFR, PTGS2, PPARG, and HSP90AA1) were further screened. The results of the enrichment analysis revealed that the main pathways through which BPA affects OA involve key signaling cascades, including the estrogen signaling pathway, the thyroid hormone signaling pathway, and the ErbB signaling pathway. The results of molecular docking and dynamic simulations indicated that there are stable binding interactions between BPA and the core targets. The results of the RT-qPCR and IHC assays revealed significant differences in the core targets between the OA group and the normal group. CONCLUSIONS: This study links the environmental toxin BPA with OA, systematically describing potential core targets and pathways. These findings emphasize the importance of reducing BPA exposure in public health, providing new insights for the formulation of subsequent environmental policies. TRIAL REGISTRATION: Not applicable.