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Updated: Jun 6, 2025
A Novel in vivo Gene Transfer Technique and in vitro Cell Based Assays for the Study of Bone Loss in Musculoskeletal Disorders
Published on: June 8, 2014
Effect of Acetyl tributyl citrate on bone metabolism based on network toxicology and molecular docking technology
1Central Laboratory, Affiliated Hospital of Putian University, Putian, Fujian Province 351100, China; Department of Environmental and Biological Engineering, Putian University, Putian, Fujian Province 351100, China.
Abstract:
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.
Insights
Acetyl tributyl citrate (ATBC) impairs osteoblast function and bone metabolism by downregulating key epigenetic regulators. This study reveals molecular mechanisms linking ATBC exposure to potential orthopedic disorders.
Area of Science:
- Environmental Health
- Molecular Biology
- Bone Metabolism
Background:
- Environmental contaminants like Acetyl tributyl citrate (ATBC) can impact human health.
- Understanding the molecular basis of ATBC's effects on bone metabolism is crucial for public health.
Purpose of the Study:
- To elucidate the molecular mechanisms of ATBC's impact on bone metabolism.
- To identify key molecular targets and signaling pathways affected by ATBC.
Main Methods:
- Bioinformatic analyses (ChEMBL, STITCH, GeneCards, OMIM, STRING, Cytoscape, Metascape) to identify ATBC targets and pathways.
- Molecular docking simulations (AutoDock) to confirm ATBC-target interactions.
- In vitro experiments using osteoblasts (MC3T3-E1) exposed to ATBC.
Main Results:
- Ten core molecular targets and several key signaling pathways (e.g., thyroid hormone, FOXO, insulin) were identified.
- Low-dose ATBC (100 μM) impaired osteoblast proliferation and migration.
- ATBC exposure downregulated key epigenetic regulators (KDM1A, EP300, HDAC2) in osteoblasts.
Conclusions:
- ATBC disrupts bone metabolism at the cellular level by affecting epigenetic regulators.
- This study provides a molecular framework for understanding ATBC-induced bone disorders.
- Findings may inform strategies for preventing orthopedic issues related to ATBC exposure.
