{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T14:08:40Z","timestamp":1792850920440,"version":"4.5.0"},"reference-count":49,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T00:00:00Z","timestamp":1772928000000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Food Science &amp; Nutrition"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Sodium Dehydroacetate (Na\u2010DHA), a widely used food additive, has raised concerns about the chronic health risks associated with long\u2010term exposure. However, the potential impact of Na\u2010DHA on bone metabolism, its contribution to osteoporosis risk, and the specific molecular mechanisms remain unclear. This study aims to systematically elucidate the molecular mechanisms through which Na\u2010DHA induces osteoporosis by integrating network toxicology, molecular docking, and in\u00a0vitro experiments. Potential targets of Na\u2010DHA were identified through multi\u2010database screening. Osteoporosis\u2010related genes were extracted from the GEO database (GSE156508) and subjected to differential and enrichment analyses. Common targets between Na\u2010DHA and osteoporosis were identified using a Venn diagram. A protein\u2013protein interaction (PPI) network was constructed using STRING, and core targets were selected through random forest analysis. Molecular docking of core targets with Na\u2010DHA was performed using AutoDock Vina. Human bone marrow mesenchymal stem cells (hBMSCs) were used as a model to assess cell viability using the CCK\u20108 assay, observe osteogenic\/adipogenic differentiation phenotypes through Alizarin Red S and Oil Red O staining, and validate the expression of core targets and osteogenic genes by qRT\u2010PCR and Western blot. Multi\u2010database screening identified 325 potential Na\u2010DHA targets and 500 osteoporosis\u2010related differential genes. Of these, 34 common key targets were identified, which were mainly enriched in pathways related to lipid metabolism, autophagy, and steroid biosynthesis. Random forest analysis identified LCMT1, ARHGEF11, and VCAM1 as core targets, and molecular docking revealed potential binding interactions between Na\u2010DHA and all three targets. In\u00a0vitro experiments demonstrated that 10\u2009\u03bcM Na\u2010DHA significantly inhibited hBMSCs viability, reduced calcium deposition in Alizarin Red S staining, increased lipid droplet accumulation in Oil Red O staining, and downregulated the expression of key osteogenic genes (\n                    <jats:italic>BGLAP<\/jats:italic>\n                    ,\n                    <jats:italic>SP7<\/jats:italic>\n                    ,\n                    <jats:italic>RUNX2<\/jats:italic>\n                    ,\n                    <jats:italic>ALPL<\/jats:italic>\n                    ). Moreover, Na\u2010DHA significantly upregulated the mRNA and protein expression of LCMT1 and downregulated the mRNA and protein expression of ARHGEF11 and VCAM1. Na\u2010DHA may increase osteoporosis risk by upregulating LCMT1, downregulating ARHGEF11 and VCAM1, and disrupting lipid metabolism and the balance between osteogenesis and adipogenesis, ultimately disrupting bone metabolic homeostasis. This study provides scientific evidence for assessing the skeletal health risks of Na\u2010DHA and exploring potential intervention targets for bone toxicity.\n                  <\/jats:p>","DOI":"10.1002\/fsn3.71633","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T17:42:39Z","timestamp":1772991759000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Study on the Potential Molecular Mechanisms of Sodium Dehydroacetate (\n                    <scp>Na\u2010DHA<\/scp>\n                    ) Interfering With Bone Metabolism and Inducing Osteoporosis Based on Network Toxicology, Molecular Docking, and In\u00a0Vitro Experimental Validation"],"prefix":"10.1002","volume":"14","author":[{"given":"Weihong","family":"Qian","sequence":"first","affiliation":[{"name":"Tongxiang Hosptial of Traditional Chinese Medicine  Tongxiang City Zhejiang Province P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingqing","family":"Bao","sequence":"additional","affiliation":[{"name":"Tongxiang Health School  Tongxiang City Zhejiang Province P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqing","family":"Tang","sequence":"additional","affiliation":[{"name":"Tongxiang Hosptial of Traditional Chinese Medicine  Tongxiang City Zhejiang Province P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wuchao","family":"Lu","sequence":"additional","affiliation":[{"name":"Tongxiang Hosptial of Traditional Chinese Medicine  Tongxiang City Zhejiang Province P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxin","family":"Huang","sequence":"additional","affiliation":[{"name":"Tongxiang Hosptial of Traditional Chinese Medicine  Tongxiang City Zhejiang Province P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiapeng","family":"Bao","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital, Zhejiang University School of Medicine  Hangzhou Zhejiang Province P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5334-1423","authenticated-orcid":false,"given":"Zhihong","family":"Yao","sequence":"additional","affiliation":[{"name":"Tongxiang Hosptial of Traditional Chinese Medicine  Tongxiang City Zhejiang Province P. R. 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