Effect of Acetyl tributyl citrate on bone metabolism based on network toxicology and molecular docking technology
This study aims to elucidate the intricate effects of Acetyl tributyl citrate (ATBC) on bone metabolism, disentangling the underlying molecular mechanisms that govern the impact of environmental contaminants on disease processes. Leveraging the exhaustive exploration of databases such as ChEMBL, STI...
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Elsevier
2025-01-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651324015100 |
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| author | Xuan Lin Kun Lin Yue Lai Qingping Peng Miao Xu Yiting Xu Jialin Yang Huan Liu Jianlin Shen |
| author_facet | Xuan Lin Kun Lin Yue Lai Qingping Peng Miao Xu Yiting Xu Jialin Yang Huan Liu Jianlin Shen |
| author_sort | Xuan Lin |
| collection | DOAJ |
| description | This study aims to elucidate the intricate effects of Acetyl tributyl citrate (ATBC) on bone metabolism, disentangling the underlying molecular mechanisms that govern the impact of environmental contaminants on disease processes. Leveraging the exhaustive exploration of databases such as ChEMBL, STITCH, GeneCards, and OMIM, we have identified a comprehensive list of 164 potential targets intimately associated with both ATBC and bone metabolism. Following rigorous refinement using the STRING platform and Cytoscape software, we pinpointed ten core targets, encompassing KDM1A, EP300, HDAC2, EHMT2, DNMT1, and several others. In-depth Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, conducted within the Metascape database, revealed that the core targets of ATBC’s influence on bone metabolism are predominantly concentrated within vital signaling cascades, including thyroid hormone signaling, FOXO signaling, glucagon signaling, AMPK signaling, insulin signaling, adipocytokine signaling, and Notch signaling pathways. Additionally, molecular docking simulations performed with AutoDock software confirmed the robust binding interactions between ATBC and these core targets, reinforcing our understanding of their interactions. To explore the cellular impact of ATBC, we performed in vitro experiments using osteoblasts (MC3T3-E1) exposed to relevant concentrations. Our findings revealed that low-dose ATBC (100 μM) significantly impaired cell proliferation and migration. Concurrently, we observed a downregulation in the transcriptional expression of key epigenetic regulators (KDM1A, EP300, HDAC2), suggesting that ATBC can disrupt bone metabolism at the cellular level. Collectively, our findings provide a theoretical scaffold for comprehending the intricate molecular mechanisms mediating ATBC’s effects on bone metabolism, and paves the way for the development of preventive and therapeutic strategies against orthopedic disorders that may arise from exposure to plastic products containing ATBC or excessive ATBC environments. |
| format | Article |
| id | doaj-art-3f3e1927ce7647b0be3c5fe0ecaa04e3 |
| institution | Kabale University |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-3f3e1927ce7647b0be3c5fe0ecaa04e32025-01-23T05:25:31ZengElsevierEcotoxicology and Environmental Safety0147-65132025-01-01289117434Effect of Acetyl tributyl citrate on bone metabolism based on network toxicology and molecular docking technologyXuan Lin0Kun Lin1Yue Lai2Qingping Peng3Miao Xu4Yiting Xu5Jialin Yang6Huan Liu7Jianlin Shen8Central Laboratory, Affiliated Hospital of Putian University, Putian, Fujian Province 351100, China; Department of Environmental and Biological Engineering, Putian University, Putian, Fujian Province 351100, ChinaDepartment of Laboratory Medicine, the Affiliated Hospital of Putian University, Putian University, Putian 351100, ChinaThe First Clinical Medical School, Guangdong Medical University, Zhanjiang, Guangdong Province 524002, ChinaCollage of Integrated Traditional Chinese and Western Medicine, Southwest Medical University, Luzhou, Sichuan Province 646000, ChinaSchool of Basic Medicine, Fujian Medical University, Fuzhou, Fujian Province 350100, ChinaDepartment of Clinical Medicine, Putian University, Putian, Fujian Province 351100, ChinaDepartment of Clinical Medicine, Putian University, Putian, Fujian Province 351100, ChinaDepartment of Orthopedics, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan Province 646000, China; Corresponding author.Central Laboratory, Affiliated Hospital of Putian University, Putian, Fujian Province 351100, China; Department of Orthopedics, Affiliated Hospital of Putian University, Putian, Fujian Province 351100, China; Corresponding author at: Central Laboratory, Affiliated Hospital of Putian University, Putian, Fujian Province 351100, China.This study aims to elucidate the intricate effects of Acetyl tributyl citrate (ATBC) on bone metabolism, disentangling the underlying molecular mechanisms that govern the impact of environmental contaminants on disease processes. Leveraging the exhaustive exploration of databases such as ChEMBL, STITCH, GeneCards, and OMIM, we have identified a comprehensive list of 164 potential targets intimately associated with both ATBC and bone metabolism. Following rigorous refinement using the STRING platform and Cytoscape software, we pinpointed ten core targets, encompassing KDM1A, EP300, HDAC2, EHMT2, DNMT1, and several others. In-depth Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, conducted within the Metascape database, revealed that the core targets of ATBC’s influence on bone metabolism are predominantly concentrated within vital signaling cascades, including thyroid hormone signaling, FOXO signaling, glucagon signaling, AMPK signaling, insulin signaling, adipocytokine signaling, and Notch signaling pathways. Additionally, molecular docking simulations performed with AutoDock software confirmed the robust binding interactions between ATBC and these core targets, reinforcing our understanding of their interactions. To explore the cellular impact of ATBC, we performed in vitro experiments using osteoblasts (MC3T3-E1) exposed to relevant concentrations. Our findings revealed that low-dose ATBC (100 μM) significantly impaired cell proliferation and migration. Concurrently, we observed a downregulation in the transcriptional expression of key epigenetic regulators (KDM1A, EP300, HDAC2), suggesting that ATBC can disrupt bone metabolism at the cellular level. Collectively, our findings provide a theoretical scaffold for comprehending the intricate molecular mechanisms mediating ATBC’s effects on bone metabolism, and paves the way for the development of preventive and therapeutic strategies against orthopedic disorders that may arise from exposure to plastic products containing ATBC or excessive ATBC environments.http://www.sciencedirect.com/science/article/pii/S0147651324015100ATBCNetwork toxicologyMolecular dockingBone metabolism |
| spellingShingle | Xuan Lin Kun Lin Yue Lai Qingping Peng Miao Xu Yiting Xu Jialin Yang Huan Liu Jianlin Shen Effect of Acetyl tributyl citrate on bone metabolism based on network toxicology and molecular docking technology Ecotoxicology and Environmental Safety ATBC Network toxicology Molecular docking Bone metabolism |
| title | Effect of Acetyl tributyl citrate on bone metabolism based on network toxicology and molecular docking technology |
| title_full | Effect of Acetyl tributyl citrate on bone metabolism based on network toxicology and molecular docking technology |
| title_fullStr | Effect of Acetyl tributyl citrate on bone metabolism based on network toxicology and molecular docking technology |
| title_full_unstemmed | Effect of Acetyl tributyl citrate on bone metabolism based on network toxicology and molecular docking technology |
| title_short | Effect of Acetyl tributyl citrate on bone metabolism based on network toxicology and molecular docking technology |
| title_sort | effect of acetyl tributyl citrate on bone metabolism based on network toxicology and molecular docking technology |
| topic | ATBC Network toxicology Molecular docking Bone metabolism |
| url | http://www.sciencedirect.com/science/article/pii/S0147651324015100 |
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