Elucidating the mechanism of phthalates induced osteoporosis through network toxicology and molecular docking
Abstracts: Objective: This study investigated the effects of plasticizers (phthalates) on the pathogenesis of osteoporosis (OP) and the associated molecular mechanisms, especially the interaction of plasticizers with key pathways. Methods: We performed differential expression analysis of different...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-02-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651325001563 |
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| author | Xiao Zhang Xi Zhu Wenbo Gu Xusheng Li Tenyao Niu Pengcheng Mao Haifeng Yuan |
| author_facet | Xiao Zhang Xi Zhu Wenbo Gu Xusheng Li Tenyao Niu Pengcheng Mao Haifeng Yuan |
| author_sort | Xiao Zhang |
| collection | DOAJ |
| description | Abstracts: Objective: This study investigated the effects of plasticizers (phthalates) on the pathogenesis of osteoporosis (OP) and the associated molecular mechanisms, especially the interaction of plasticizers with key pathways. Methods: We performed differential expression analysis of different datasets by machine learning to identify target genes associated with OP. And, we also investigated the binding of plasticizers to target proteins using network toxicology and molecular docking techniques. Results: A total of 29 genes are potential targets associated with plasticizer-induced OP. Subsequently, machine learning analysis identified six core target genes as key genes for plasticizer-induced OP. Among them, the up-regulated genes were CKM and SOAT2, and the down-regulated genes were TACR3, SGK1, ERAP2, and MMP12 (P＜0.05). Molecular docking revealed the specific binding effect between plasticizers and target proteins. Conclusion: This study demonstrates that plasticizers may influence the pathogenesis of OP by targeting specific genes and pathways. And the molecular docking simulations indicate a distinct binding specificity between plasticizers and target proteins. These results provide a foundation for further investigation into the mechanisms by which plasticizers affect bone health. Future research should focus on the dose-response relationship between plasticizer exposure and the risk of OP, and explore potential intervention measures to mitigate the adverse effects of plasticizers on bone health. |
| format | Article |
| id | doaj-art-bca6603b65514c2aacc5d00e4e44e20c |
| institution | Kabale University |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-bca6603b65514c2aacc5d00e4e44e20c2025-01-31T05:10:01ZengElsevierEcotoxicology and Environmental Safety0147-65132025-02-01291117820Elucidating the mechanism of phthalates induced osteoporosis through network toxicology and molecular dockingXiao Zhang0Xi Zhu1Wenbo Gu2Xusheng Li3Tenyao Niu4Pengcheng Mao5Haifeng Yuan6General Hospital of Ningxia Medical University, Ningxia 750001, China; The First Clinical Medical College of Ningxia Medical University, Ningxia 750001, ChinaGeneral Hospital of Ningxia Medical University, Ningxia 750001, ChinaGeneral Hospital of Ningxia Medical University, Ningxia 750001, ChinaGeneral Hospital of Ningxia Medical University, Ningxia 750001, ChinaGeneral Hospital of Ningxia Medical University, Ningxia 750001, ChinaThe First Clinical Medical College of Ningxia Medical University, Ningxia 750001, ChinaGeneral Hospital of Ningxia Medical University, Ningxia 750001, China; The First Clinical Medical College of Ningxia Medical University, Ningxia 750001, China; Correspondence to: Department of Orthopaedics, General Hospital of Ningxia Medical University, Ningxia 750001, China.Abstracts: Objective: This study investigated the effects of plasticizers (phthalates) on the pathogenesis of osteoporosis (OP) and the associated molecular mechanisms, especially the interaction of plasticizers with key pathways. Methods: We performed differential expression analysis of different datasets by machine learning to identify target genes associated with OP. And, we also investigated the binding of plasticizers to target proteins using network toxicology and molecular docking techniques. Results: A total of 29 genes are potential targets associated with plasticizer-induced OP. Subsequently, machine learning analysis identified six core target genes as key genes for plasticizer-induced OP. Among them, the up-regulated genes were CKM and SOAT2, and the down-regulated genes were TACR3, SGK1, ERAP2, and MMP12 (P＜0.05). Molecular docking revealed the specific binding effect between plasticizers and target proteins. Conclusion: This study demonstrates that plasticizers may influence the pathogenesis of OP by targeting specific genes and pathways. And the molecular docking simulations indicate a distinct binding specificity between plasticizers and target proteins. These results provide a foundation for further investigation into the mechanisms by which plasticizers affect bone health. Future research should focus on the dose-response relationship between plasticizer exposure and the risk of OP, and explore potential intervention measures to mitigate the adverse effects of plasticizers on bone health.http://www.sciencedirect.com/science/article/pii/S0147651325001563PlasticizersPhthalatesOsteoporosisMolecular dockingBioinformaticsMachine learning |
| spellingShingle | Xiao Zhang Xi Zhu Wenbo Gu Xusheng Li Tenyao Niu Pengcheng Mao Haifeng Yuan Elucidating the mechanism of phthalates induced osteoporosis through network toxicology and molecular docking Ecotoxicology and Environmental Safety Plasticizers Phthalates Osteoporosis Molecular docking Bioinformatics Machine learning |
| title | Elucidating the mechanism of phthalates induced osteoporosis through network toxicology and molecular docking |
| title_full | Elucidating the mechanism of phthalates induced osteoporosis through network toxicology and molecular docking |
| title_fullStr | Elucidating the mechanism of phthalates induced osteoporosis through network toxicology and molecular docking |
| title_full_unstemmed | Elucidating the mechanism of phthalates induced osteoporosis through network toxicology and molecular docking |
| title_short | Elucidating the mechanism of phthalates induced osteoporosis through network toxicology and molecular docking |
| title_sort | elucidating the mechanism of phthalates induced osteoporosis through network toxicology and molecular docking |
| topic | Plasticizers Phthalates Osteoporosis Molecular docking Bioinformatics Machine learning |
| url | http://www.sciencedirect.com/science/article/pii/S0147651325001563 |
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