Elucidating the mechanism of polycyclic aromatic hydrocarbons-induced osteoporosis through network toxicology and molecular docking approaches: BaP as a model compound.

This work showcases a network‑toxicology strategy to uncover the osteotoxic effects and molecular pathways of polycyclic aromatic hydrocarbons, using BaP‑induced osteoporosis as a model. Potential targets of BaP were extracted from the Comparative Toxicogenomics Database (CTD) and ChEMBL, while osteoporosis-related targets were obtained from GeneCards. A total of 93 overlapping genes between osteoporosis-related targets and BaP-perturbed genes were identified. Subsequent protein-protein interaction (PPI) network analysis was constructed using STRING and visualized with Cytoscape. Seven core genes were identified: COL1A1, COL5A1, COL4A3, COL2A1, COL1A2, COL4A1, and COL5A2 via the Maximum Clique Centrality (MCC) algorithm. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses conducted in R indicated that BaP-induced osteoporosis involves extracellular matrix organization, cellular response to xenobiotic stimuli, the PI3K-Akt signaling pathway, protein digestion and absorption, and cytoskeletal regulation. Molecular docking performed using AutoDock confirmed strong binding affinities between BaP and these core targets. Collectively, these results suggest that BaP-activated signaling cascades, particularly the ECM remodeling genes and PI3K-Akt pathway, may converge to influence osteoblast/osteoclast activity and bone homeostasis, offering a mechanistic basis for its role in osteoporosis and a new angle for evaluating pollutant‑related health risks.