ORIGINAL RESEARCH article
Front. Toxicol.
Sec. Environmental Toxicology
Volume 7 - 2025 | doi: 10.3389/ftox.2025.1617663
Exploring Plasticisers-Osteoporosis Links and Mechanisms: A Cohort and Network Toxicology Study
Provisionally accepted
- 1Chengdu Fifth People's Hospital, Chengdu, China
- 2Chuanbei Medical College, Sichuan, China
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Background: Plasticisers, widely present in daily life, have been linked to osteoporosis (OP), though the precise mechanisms remain unclear. Methods: This study examined the association between mono(2-ethylhexyl) phthalate (MEHP) and OP using multivariate logistic regression based on NHANES data. Network toxicology identified key targets and pathways involved in MEHP-induced OP. Molecular docking and dynamics simulations validated the stability of MEHP-target interactions. The effects of MEHP on osteogenic differentiation were further assessed in mouse bone marrow stromal cells (BMSCs). Results: All logistic regression models confirmed a significant positive correlation between MEHP levels and OP. Network toxicology analysis identified CTSD, SOAT1, and VCP as key targets and the apoptosis pathway as a key mechanism in MEHP-induced OP. Molecular simulations demonstrated stable MEHP binding to these targets. Cellular experiments revealed that MEHP significantly inhibited BMSC osteogenesis by downregulating CTSD and VCP, while SOAT1 showed a weaker correlation. Conclusion: MEHP exposure is positively associated with OP risk, with CTSD, VCP, and the apoptosis pathway potentially playing key roles in impairing BMSC osteogenesis.
Keywords: plasticiser, Osteoporosis, NHANES, molecular docking, Molecular Dynamics Simulation
Received: 24 Apr 2025; Accepted: 04 Aug 2025.
Copyright: © 2025 Yang, Wang, Bao, Li, Xing and Du. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Zhangzhen Du, Chengdu Fifth People's Hospital, Chengdu, China
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