{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T11:39:29Z","timestamp":1792409969683,"version":"4.4.0"},"reference-count":38,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T00:00:00Z","timestamp":1792368000000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"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":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Postmenopausal osteoporosis (PMOP) and its associated fracture complications have emerged as pressing public health challenges due to rapidly accelerating global population ageing. The functional decline of bone marrow mesenchymal stem cells (BMSCs) under elevated oxidative stress is a recognised pathogenic cornerstone of PMOP, positioning redox imbalance as a critical therapeutic node. Here, we establish that sodium selenite (Na\n                    <jats:sub>2<\/jats:sub>\n                    SeO\n                    <jats:sub>3<\/jats:sub>\n                    ) robustly counters oxidative insults in BMSCs, thereby restoring and enhancing their osteogenic lineage commitment. Furthermore, RNA sequencing analysis indicated that ferroptosis may be mechanistically associated with the underlying cellular responses. Ferroptosis is critically mediated by glutathione peroxidase 4 (GPX4), a selenoenzyme that functions as its principal enzymatic suppressor. Silencing GPX4 in BMSCs markedly reduced their osteogenic capacity and simultaneously upregulated ferroptotic protein expression. Notably, this impairment was not reversed by Na\n                    <jats:sub>2<\/jats:sub>\n                    SeO\n                    <jats:sub>3<\/jats:sub>\n                    administration under conditions of GPX4 suppression. These findings suggest that Na\n                    <jats:sub>2<\/jats:sub>\n                    SeO\n                    <jats:sub>3<\/jats:sub>\n                    enhances osteogenic differentiation primarily by upregulating GPX4 expression, thereby inhibiting ferroptosis. Thus, we have established Na\n                    <jats:sub>2<\/jats:sub>\n                    SeO\n                    <jats:sub>3<\/jats:sub>\n                    as a potential therapeutic strategy for PMOP by identifying a previously unrecognised molecular axis through which selenium regulates bone metabolic homeostasis.\n                  <\/jats:p>","DOI":"10.1111\/jcmm.71414","type":"journal-article","created":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T10:40:38Z","timestamp":1792406438000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>GPX4<\/scp>\n                    \u2010Mediated Inhibition of Ferroptosis by Sodium Selenite Ameliorates Bone Metabolic Disorders in Ovariectomized Mice"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-4244-9785","authenticated-orcid":false,"given":"Wei","family":"Luo","sequence":"first","affiliation":[{"name":"The Department of Orthopedic Surgery The Fourth Affiliated Hospital of Soochow University (Suzhou Dushu Lake Hospital)  Suzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibo","family":"Xu","sequence":"additional","affiliation":[{"name":"The Department of Orthopedic Surgery Taizhou Fourth People's Hospital  Taizhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8681-5096","authenticated-orcid":false,"given":"Xin","family":"Liu","sequence":"additional","affiliation":[{"name":"The Department of Orthopaedic Surgery, Orthopaedic Institute, the First Affiliated Hospital, Suzhou Medical College Soochow University  Suzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongsheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Department of Orthopedic Surgery The Fourth Affiliated Hospital of Soochow University (Suzhou Dushu Lake Hospital)  Suzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Zhou","sequence":"additional","affiliation":[{"name":"The Department of Orthopedic Surgery The Fourth Affiliated Hospital of Soochow University (Suzhou Dushu Lake Hospital)  Suzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4865-9763","authenticated-orcid":false,"given":"Xiangqiang","family":"Pan","sequence":"additional","affiliation":[{"name":"College of Chemistry Chemical Engineering and Materials Science Soochow University  Suzhou People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4375-2803","authenticated-orcid":false,"given":"Dechun","family":"Geng","sequence":"additional","affiliation":[{"name":"The Department of Orthopaedic Surgery, Orthopaedic Institute, the First Affiliated Hospital, Suzhou Medical College Soochow University  Suzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4890-5209","authenticated-orcid":false,"given":"Hanliang","family":"He","sequence":"additional","affiliation":[{"name":"The Department of Orthopedic Surgery The Fourth Affiliated Hospital of Soochow University (Suzhou Dushu Lake Hospital)  Suzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,19]]},"reference":[{"issue":"21","key":"e_1_2_14_2_1","doi-asserted-by":"crossref","first-page":"1979","DOI":"10.1056\/NEJMcp2307353","article-title":"Postmenopausal Osteoporosis","volume":"389","author":"Walker M. D.","year":"2023","journal-title":"New England Journal of Medicine"},{"key":"e_1_2_14_3_1","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2024.1456796","article-title":"Osteoporosis Treatment: Current Drugs and Future Developments","volume":"15","author":"Chen Y.\u2010j.","year":"2024","journal-title":"Frontiers in Pharmacology"},{"issue":"1","key":"e_1_2_14_4_1","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1080\/13697137.2021.1951697","article-title":"Medical Treatment of Osteoporosis","volume":"25","author":"Palacios S.","year":"2022","journal-title":"Climacteric"},{"issue":"5","key":"e_1_2_14_5_1","doi-asserted-by":"crossref","DOI":"10.3390\/biom13050799","article-title":"Selenium and Selenoproteins in Health","volume":"13","author":"Zhang F.","year":"2023","journal-title":"Biomolecules"},{"key":"e_1_2_14_6_1","doi-asserted-by":"crossref","DOI":"10.1093\/rb\/rbad011","article-title":"Selenium\u2010Modified Bone Cement Promotes Osteoporotic Bone Defect Repair in Ovariectomized Rats by Restoring GPx1\u2010Mediated Mitochondrial Antioxidant Functions","volume":"10","author":"Zhou Q.","year":"2023","journal-title":"Regenerative Biomaterials"},{"issue":"11","key":"e_1_2_14_7_1","doi-asserted-by":"crossref","first-page":"7026","DOI":"10.1111\/ijfs.16096","article-title":"Selenium and Selenoproteins: Their Function and Development of Selenium\u2010Rich Foods","volume":"57","author":"Han M.","year":"2022","journal-title":"International Journal of Food Science & Technology"},{"issue":"2","key":"e_1_2_14_8_1","doi-asserted-by":"crossref","DOI":"10.1038\/s41419-020-2298-2","article-title":"Ferroptosis: Past, Present and Future","volume":"11","author":"Li J.","year":"2020","journal-title":"Cell Death & Disease"},{"issue":"1","key":"e_1_2_14_9_1","doi-asserted-by":"crossref","DOI":"10.1038\/s41392-024-02088-5","article-title":"In Defence of Ferroptosis","volume":"10","author":"Alves F.","year":"2025","journal-title":"Signal Transduction and Targeted Therapy"},{"issue":"22","key":"e_1_2_14_10_1","doi-asserted-by":"crossref","first-page":"5565","DOI":"10.1111\/jcmm.17529","article-title":"Ferroptosis in Tumor Immunity and Therapy","volume":"26","author":"Gong C.","year":"2022","journal-title":"Journal of Cellular and Molecular Medicine"},{"issue":"1","key":"e_1_2_14_11_1","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.jcmgh.2023.03.001","article-title":"Ferroptosis Suppressor Protein 1 Inhibition Promotes Tumor Ferroptosis and Anti\u2010Tumor Immune Responses in Liver Cancer","volume":"16","author":"Cheu J. W.\u2010S.","year":"2023","journal-title":"Cellular and Molecular Gastroenterology and Hepatology"},{"issue":"4","key":"e_1_2_14_12_1","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.ccell.2024.03.011","article-title":"The Roles of Ferroptosis in Cancer: Tumor Suppression, Tumor Microenvironment, and Therapeutic Interventions","volume":"42","author":"Lei G.","year":"2024","journal-title":"Cancer Cell"},{"issue":"1","key":"e_1_2_14_13_1","doi-asserted-by":"crossref","DOI":"10.1007\/s10571-024-01457-6","article-title":"Progress of Ferroptosis in Ischemic Stroke and Therapeutic Targets","volume":"44","author":"Tian X.","year":"2024","journal-title":"Cellular and Molecular Neurobiology"},{"issue":"9","key":"e_1_2_14_14_1","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.4103\/1673-5374.390960","article-title":"Metformin Alleviates Spinal Cord Injury by Inhibiting Nerve Cell Ferroptosis Through Upregulation of Heme Oxygenase\u20101 Expression","volume":"19","author":"Wang Z.","year":"2024","journal-title":"Neural Regeneration Research"},{"issue":"9","key":"e_1_2_14_15_1","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1055\/a-2230-2664","article-title":"Ferroptosis: A Frontier in Osteoporosis","volume":"56","author":"Maheshwari S.","year":"2024","journal-title":"Hormone and Metabolic Research"},{"key":"e_1_2_14_16_1","doi-asserted-by":"crossref","DOI":"10.1155\/2022\/3568597","article-title":"The Regulatory Role of Ferroptosis in Bone Homeostasis","volume":"2022","author":"Xiong Y.","year":"2022","journal-title":"Stem Cells International"},{"issue":"39","key":"e_1_2_14_17_1","doi-asserted-by":"crossref","DOI":"10.1097\/MD.0000000000039158","article-title":"Ferroptosis: Regulatory Mechanisms and Potential Targets for Bone Metabolism: A Review","volume":"103","author":"Zhang Y.","year":"2024","journal-title":"Medicine"},{"issue":"3","key":"e_1_2_14_18_1","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1042\/BST20220682","article-title":"GPX4: Old Lessons, New Features","volume":"50","author":"Nishida Xavier da Silva T.","year":"2022","journal-title":"Biochemical Society Transactions"},{"issue":"3","key":"e_1_2_14_19_1","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.freeradbiomed.2020.02.027","article-title":"Lipid Peroxidation and Ferroptosis: The Role of GSH and GPX4","volume":"152","author":"Ursini F.","year":"2020","journal-title":"Free Radical Biology and Medicine"},{"issue":"21","key":"e_1_2_14_20_1","doi-asserted-by":"crossref","DOI":"10.3390\/ijms222111844","article-title":"Antitumor Effects of Selenium","volume":"22","author":"Kim S. J.","year":"2021","journal-title":"International Journal of Molecular Sciences"},{"issue":"6","key":"e_1_2_14_21_1","doi-asserted-by":"crossref","first-page":"3253","DOI":"10.1007\/s11010-024-05202-x","article-title":"Selenium: 48\u2010Year Journey of Global Clinical Trials","volume":"480","author":"Wu Y.","year":"2025","journal-title":"Molecular and Cellular Biochemistry"},{"issue":"4","key":"e_1_2_14_22_1","first-page":"3425","article-title":"Protective Role of Selenium on Thyroid Morphology in Iodine\u2010Induced Autoimmune Thyroiditis in Wistar Rats","volume":"20","author":"Vasiliu I.","year":"2020","journal-title":"Experimental and Therapeutic Medicine"},{"issue":"7","key":"e_1_2_14_23_1","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.joca.2012.02.012","article-title":"Sodium Selenite for Treatment of Kashin\u2010Beck Disease in Children: A Systematic Review of Randomised Controlled Trials","volume":"20","author":"Jirong Y.","year":"2012","journal-title":"Osteoarthritis and Cartilage"},{"issue":"8","key":"e_1_2_14_24_1","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1007\/s00109-025-02563-8","article-title":"Selenium and Selenoproteins: Key Regulators of Ferroptosis and Therapeutic Targets in Cancer","volume":"103","author":"Lee J.","year":"2025","journal-title":"Journal of Molecular Medicine"},{"key":"e_1_2_14_25_1","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2023.1251838","article-title":"Association of Selenium Intake With Bone Mineral Density and Osteoporosis: The National Health and Nutrition Examination Survey","volume":"14","author":"Peng S.","year":"2023","journal-title":"Frontiers in Endocrinology"},{"issue":"1","key":"e_1_2_14_26_1","doi-asserted-by":"crossref","DOI":"10.1038\/s41420-022-01212-0","article-title":"GPX4\u2010Independent Ferroptosis\u2014A New Strategy in Disease's Therapy","volume":"8","author":"Ma T.","year":"2022","journal-title":"Cell Death Discovery"},{"issue":"8","key":"e_1_2_14_27_1","doi-asserted-by":"crossref","first-page":"741","DOI":"10.2106\/JBJS.20.01248","article-title":"Osteoporosis: Recent Recommendations and Positions of the American Society for Bone and Mineral Research and the International Society for Clinical Densitometry","volume":"103","author":"Anderson P. A.","year":"2021","journal-title":"Journal of Bone and Joint Surgery"},{"issue":"7674","key":"e_1_2_14_28_1","doi-asserted-by":"crossref","first-page":"S15","DOI":"10.1038\/550S15a","article-title":"Staying strong","volume":"550","author":"Brown C.","year":"2017","journal-title":"Nature"},{"issue":"4","key":"e_1_2_14_29_1","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1007\/s11914-017-0376-x","article-title":"Using Osteoporosis Therapies in Combination","volume":"15","author":"McClung M. R.","year":"2017","journal-title":"Current Osteoporosis Reports"},{"issue":"12","key":"e_1_2_14_30_1","doi-asserted-by":"crossref","first-page":"2702","DOI":"10.4103\/1673-5374.339491","article-title":"Sodium Selenite Promotes Neurological Function Recovery After Spinal Cord Injury by Inhibiting Ferroptosis","volume":"17","author":"Chen Y.\u2010X.","year":"2022","journal-title":"Neural Regeneration Research"},{"key":"e_1_2_14_31_1","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2023.1133000","article-title":"Selenium and Thyroid Diseases","volume":"14","author":"Wang F.","year":"2023","journal-title":"Frontiers in Endocrinology"},{"issue":"3","key":"e_1_2_14_32_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.chempr.2025.102493","article-title":"Selenium Nanomedicine: From Basic Science to Clinical Applications","volume":"11","author":"He L.","year":"2025","journal-title":"Chem"},{"issue":"4","key":"e_1_2_14_33_1","doi-asserted-by":"crossref","DOI":"10.3390\/metabo12040274","article-title":"Selenium Levels and Antioxidant Activity in Critically Ill Patients With Systemic Inflammatory Response Syndrome","volume":"12","author":"Herrera\u2010Quintana L.","year":"2022","journal-title":"Metabolites"},{"key":"e_1_2_14_34_1","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2022.941618","article-title":"Lipid Metabolism in Ferroptosis and Ferroptosis\u2010Based Cancer Therapy","volume":"12","author":"Sun Y.","year":"2022","journal-title":"Frontiers in Oncology"},{"issue":"11","key":"e_1_2_14_35_1","doi-asserted-by":"crossref","first-page":"4570","DOI":"10.1021\/acs.analchem.3c05430","article-title":"Reversible Dual Fluorescence\u2010Lifetime Imaging of Mitochondrial GSH and Microviscosity: Real\u2010Time Evaluation of Ferroptosis Status","volume":"96","author":"Wang S.\u2010Y.","year":"2024","journal-title":"Analytical Chemistry"},{"issue":"9","key":"e_1_2_14_36_1","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1038\/s41590-021-00996-0","article-title":"Selenium\u2013GPX4 Axis Protects Follicular Helper T Cells From Ferroptosis","volume":"22","author":"Yao Y.","year":"2021","journal-title":"Nature Immunology"},{"key":"e_1_2_14_37_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2024.116512","article-title":"GPX4, Ferroptosis, and Diseases","volume":"174","author":"Zhang W.","year":"2024","journal-title":"Biomedicine & Pharmacotherapy"},{"issue":"10","key":"e_1_2_14_38_1","doi-asserted-by":"crossref","first-page":"2621","DOI":"10.1080\/15548627.2023.2218764","article-title":"GPX4 in Cell Death, Autophagy, and Disease","volume":"19","author":"Xie Y.","year":"2023","journal-title":"Autophagy"},{"issue":"11","key":"e_1_2_14_39_1","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1007\/s00018-016-2194-1","article-title":"Mechanisms of Ferroptosis","volume":"73","author":"Cao J. Y.","year":"2016","journal-title":"Cellular and Molecular Life Sciences"}],"container-title":["Journal of Cellular and Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.71414","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jcmm.71414","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.71414","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T10:40:51Z","timestamp":1792406451000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jcmm.71414"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":38,"journal-issue":{"issue":"20","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1111\/jcmm.71414"],"URL":"https:\/\/doi.org\/10.1111\/jcmm.71414","archive":["Portico"],"relation":{},"ISSN":["1582-1838","1582-4934"],"issn-type":[{"value":"1582-1838","type":"print"},{"value":"1582-4934","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"2026-08-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e71414"}}