Tobacco induced diseases · 2026
Unraveling the mechanisms of nicotine-induced osteoporosis via network toxicology, bioinformatics, and molecular docking.
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Xu Song, Wang Guozhu, Liu Jiaxin, Zhang Xiongwen, Dong Xie, Liang Jin, Bai Tao
Аннотация
INTRODUCTION: Osteoporosis (OP) is linked to smoking. Nicotine may disrupt bone homeostasis through various pathways, but its molecular mechanisms are unclear. This study aims to explore the molecular networks and key regulatory factors underlying nicotine-induced OP.
METHODS: Nicotine toxicity was assessed via ProTox-3.0, with its Simplified Molecular Input Line Entry System (SMILES) structure retrieved from PubChem. Potential targets were predicted using five databases, including SuperPred. OP-related gene data (GSE56815) were extracted from Gene Expression Omnibus (GEO) and combined with GeneCards and Comparative Toxicogenomics Database (CTD) for target screening. Overlapping genes were identified by Venn diagram analysis, followed by protein-protein interaction (PPI) network construction. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using HipLot, while Hallmark Gene Sets provided insights into key biological pathways. Core targets were screened via Cytoscape 3.9.1, and molecular docking was conducted using AutoDockTools 1.5.7.
RESULTS: In all, 388 nicotine-associated targets and 1777 OP genes were predicted, with 116 overlapping. Enrichment analyses revealed associations with multiple signaling pathways, particularly those involving apoptosis and estrogen. Eight core targets, including SRC, BCL2, and CASP3, were identified. Molecular docking showed strong binding affinity (approximately -5 kcal/mol), with enhanced binding stability through hydrophobic interactions and hydrogen bonding.
CONCLUSIONS: This study suggests nicotine exacerbates OP by regulating key targets, such as CASP3 and ESR1, and pathways like apoptosis and estrogen signaling. These findings provide insights into the molecular mechanisms underlying nicotine's role in OP and potential therapeutic targets.
METHODS: Nicotine toxicity was assessed via ProTox-3.0, with its Simplified Molecular Input Line Entry System (SMILES) structure retrieved from PubChem. Potential targets were predicted using five databases, including SuperPred. OP-related gene data (GSE56815) were extracted from Gene Expression Omnibus (GEO) and combined with GeneCards and Comparative Toxicogenomics Database (CTD) for target screening. Overlapping genes were identified by Venn diagram analysis, followed by protein-protein interaction (PPI) network construction. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using HipLot, while Hallmark Gene Sets provided insights into key biological pathways. Core targets were screened via Cytoscape 3.9.1, and molecular docking was conducted using AutoDockTools 1.5.7.
RESULTS: In all, 388 nicotine-associated targets and 1777 OP genes were predicted, with 116 overlapping. Enrichment analyses revealed associations with multiple signaling pathways, particularly those involving apoptosis and estrogen. Eight core targets, including SRC, BCL2, and CASP3, were identified. Molecular docking showed strong binding affinity (approximately -5 kcal/mol), with enhanced binding stability through hydrophobic interactions and hydrogen bonding.
CONCLUSIONS: This study suggests nicotine exacerbates OP by regulating key targets, such as CASP3 and ESR1, and pathways like apoptosis and estrogen signaling. These findings provide insights into the molecular mechanisms underlying nicotine's role in OP and potential therapeutic targets.