基于网络毒理学和分子对接技术研究双酚A对骨代谢的影响OA

Objective To explore the molecular mechanism underlying the effects of bisphenol A(BPA)on bone metabolism via network toxicology and molecular docking approaches.Methods By integrating data from the ChEM-BL,STITCH and SwissTargetPrediction drug target databases and GeneCards,OMIM and TTD disease-related databases,potential targets that were significantly associated with both BPA exposure and bone metabolism were screened out.Subse-quently,the core targets were identified by STRING and Cytoscape software.In the DAVID database,a comprehensive analysis of gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)pathways was applied to obtain the relevant pathways that were mainly enriched in the core targets of BPA affecting bone metabolism.Subsequently,the five core targets were validated by molecular docking.Results A total of 92 potential targets of BPA affecting bone metabolism were identified,and five core genes related to bone metabolism were further identified by STRING and Cytoscape:KRAS,CYP1A1,TNF,JAK2 and UGT2B17.The enrichment analysis yielded a total of 87 biological processes(BPs),32 cellular components(CCs),109 molecular functions(MFs)and 86 signaling pathways associated with BPA-induced bone metabolism abnormalities.Molecular docking demonstrated a high binding affinity between BPA and the core genes.Conclusion BPA may affect bone metabolism through signaling pathways such as transforming growth factor-beta(TGF-β),mitogen-activated protein kinase(MAPK)and steroid hormone biosynthesis.