Efficient evaluation of osteotoxicity and mechanisms of endocrine disrupting chemicals using network toxicology and molecular docking approaches: triclosan as a model compound
This study aimed to demonstrate the utility of a network toxicology strategy in elucidating osteotoxicity and the molecular mechanisms of endocrine-disrupting chemicals (EDCs) using triclosan exposure in postmenopausal osteoporosis (PMOP) as a case study. The potential targets of triclosan were iden...
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Elsevier
2025-03-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651325003665 |
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| author | Zhongyuan Wang Jian Wang Qiang Fu Hui Zhao Zaijun Wang Yuzhong Gao |
| author_facet | Zhongyuan Wang Jian Wang Qiang Fu Hui Zhao Zaijun Wang Yuzhong Gao |
| author_sort | Zhongyuan Wang |
| collection | DOAJ |
| description | This study aimed to demonstrate the utility of a network toxicology strategy in elucidating osteotoxicity and the molecular mechanisms of endocrine-disrupting chemicals (EDCs) using triclosan exposure in postmenopausal osteoporosis (PMOP) as a case study. The potential targets of triclosan were identified using the Comparative Toxicogenomics Database, SwissTargetPrediction, and TargetNet. PMOP-related targets were obtained from GeneCards, DisGeNET, and DrugBank. A total of 478 overlapping genes between disease targets and triclosan effectors were identified. Subsequent analysis using STRING and Cytoscape, applying the Matthews correlation coefficient algorithm, identified five core genes: STAT3, TP53, EGFR, MYC, and JUN. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses performed using R revealed that triclosan-induced PMOP is primarily associated with disrupted endocrine signaling and activation of the Phosphoinositide 3-kinase (PI3K)-Protein kinase B (Akt) signaling pathway. Molecular docking using CB-Dock2 confirmed strong binding affinities between triclosan and the core targets. Collectively, these results indicate that triclosan adversely affects bone health by disrupting endocrine regulation and energy metabolism through the PI3K-Akt pathway. This study establishes a theoretical framework for understanding how long-term triclosan exposure induces or exacerbates PMOP by investigating the underlying molecular mechanisms. These findings present a novel paradigm for evaluating the health risks posed by environmental pollutants. |
| format | Article |
| id | doaj-art-cdb1ff4b002b48a4a4b853971fe21d19 |
| institution | DOAJ |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-cdb1ff4b002b48a4a4b853971fe21d192025-08-20T02:50:48ZengElsevierEcotoxicology and Environmental Safety0147-65132025-03-0129311803010.1016/j.ecoenv.2025.118030Efficient evaluation of osteotoxicity and mechanisms of endocrine disrupting chemicals using network toxicology and molecular docking approaches: triclosan as a model compoundZhongyuan Wang0Jian Wang1Qiang Fu2Hui Zhao3Zaijun Wang4Yuzhong Gao5Department of orthopaedics, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121000, ChinaDepartment of orthopaedics, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121000, ChinaDepartment of orthopaedics, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121000, ChinaDepartment of orthopaedics, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121000, ChinaDepartment of orthopaedics, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121000, ChinaCorresponding author.; Department of orthopaedics, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121000, ChinaThis study aimed to demonstrate the utility of a network toxicology strategy in elucidating osteotoxicity and the molecular mechanisms of endocrine-disrupting chemicals (EDCs) using triclosan exposure in postmenopausal osteoporosis (PMOP) as a case study. The potential targets of triclosan were identified using the Comparative Toxicogenomics Database, SwissTargetPrediction, and TargetNet. PMOP-related targets were obtained from GeneCards, DisGeNET, and DrugBank. A total of 478 overlapping genes between disease targets and triclosan effectors were identified. Subsequent analysis using STRING and Cytoscape, applying the Matthews correlation coefficient algorithm, identified five core genes: STAT3, TP53, EGFR, MYC, and JUN. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses performed using R revealed that triclosan-induced PMOP is primarily associated with disrupted endocrine signaling and activation of the Phosphoinositide 3-kinase (PI3K)-Protein kinase B (Akt) signaling pathway. Molecular docking using CB-Dock2 confirmed strong binding affinities between triclosan and the core targets. Collectively, these results indicate that triclosan adversely affects bone health by disrupting endocrine regulation and energy metabolism through the PI3K-Akt pathway. This study establishes a theoretical framework for understanding how long-term triclosan exposure induces or exacerbates PMOP by investigating the underlying molecular mechanisms. These findings present a novel paradigm for evaluating the health risks posed by environmental pollutants.http://www.sciencedirect.com/science/article/pii/S0147651325003665TriclosanNetwork toxicologyPostmenopausal osteoporosisMolecular docking |
| spellingShingle | Zhongyuan Wang Jian Wang Qiang Fu Hui Zhao Zaijun Wang Yuzhong Gao Efficient evaluation of osteotoxicity and mechanisms of endocrine disrupting chemicals using network toxicology and molecular docking approaches: triclosan as a model compound Ecotoxicology and Environmental Safety Triclosan Network toxicology Postmenopausal osteoporosis Molecular docking |
| title | Efficient evaluation of osteotoxicity and mechanisms of endocrine disrupting chemicals using network toxicology and molecular docking approaches: triclosan as a model compound |
| title_full | Efficient evaluation of osteotoxicity and mechanisms of endocrine disrupting chemicals using network toxicology and molecular docking approaches: triclosan as a model compound |
| title_fullStr | Efficient evaluation of osteotoxicity and mechanisms of endocrine disrupting chemicals using network toxicology and molecular docking approaches: triclosan as a model compound |
| title_full_unstemmed | Efficient evaluation of osteotoxicity and mechanisms of endocrine disrupting chemicals using network toxicology and molecular docking approaches: triclosan as a model compound |
| title_short | Efficient evaluation of osteotoxicity and mechanisms of endocrine disrupting chemicals using network toxicology and molecular docking approaches: triclosan as a model compound |
| title_sort | efficient evaluation of osteotoxicity and mechanisms of endocrine disrupting chemicals using network toxicology and molecular docking approaches triclosan as a model compound |
| topic | Triclosan Network toxicology Postmenopausal osteoporosis Molecular docking |
| url | http://www.sciencedirect.com/science/article/pii/S0147651325003665 |
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