{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T21:25:51Z","timestamp":1791840351857,"version":"4.3.4"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T00:00:00Z","timestamp":1756857600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004829","name":"Science and Technology Department of Sichuan Province","doi-asserted-by":"publisher","award":["24NSFSC1606 2023ZYFS0235"],"award-info":[{"award-number":["24NSFSC1606 2023ZYFS0235"]}],"id":[{"id":"10.13039\/501100004829","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Toxicol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Plasticisers, widely present in daily life, have been linked to osteoporosis (OP), though the precise mechanisms remain unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>MEHP exposure is positively associated with OP risk, with CTSD, VCP, and the apoptosis pathway potentially playing key roles in impairing BMSC osteogenesis.<\/jats:p><\/jats:sec>","DOI":"10.3389\/ftox.2025.1617663","type":"journal-article","created":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T05:39:09Z","timestamp":1756877949000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Exploring plasticisers-osteoporosis links and mechanisms: a cohort and network toxicology study"],"prefix":"10.3389","volume":"7","author":[{"given":"Xingyao","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shifu","family":"Bao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengjiang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuxing","family":"Xing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhangzhen","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"578","DOI":"10.3390\/metabo13040578","article-title":"Influence of cholesterol on the regulation of osteoblast function","volume":"13","author":"Akhmetshina","year":"2023","journal-title":"Metabolites"},{"key":"B2","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1007\/s11914-024-00889-9","article-title":"Air pollution and osteoporosis","volume":"22","author":"Allen","year":"2024","journal-title":"Curr. 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