{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:59:22Z","timestamp":1790125162776,"version":"4.0.1"},"reference-count":52,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82401843"],"award-info":[{"award-number":["82401843"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017596","name":"Natural Science Basic Research Program of Shaanxi Province","doi-asserted-by":"publisher","award":["2024JC\u2010YBQN\u20100846"],"award-info":[{"award-number":["2024JC\u2010YBQN\u20100846"]}],"id":[{"id":"10.13039\/501100017596","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Dysregulated proliferation and differentiation of bone marrow mesenchymal stem cells (BMSCs) represent a key pathophysiological mechanism in osteoporosis. Recent studies have demonstrated a significant association between ferroptosis and the advancement of osteoporosis, suggesting that targeting ferroptosis could offer novel therapeutic approaches for osteoporosis treatment. Curcumin, a natural antioxidant, has shown therapeutic potential in bone\u2010related disorders; however, its precise mechanisms for modulating BMSC function\u2014particularly via ferroptosis\u2010related pathways\u2014remain poorly characterized. This study investigated whether curcumin alleviates iron overload\u2010induced BMSC dysfunction by targeting ferroptosis, specifically elucidating its molecular mechanisms in promoting osteogenic differentiation and mitigating cellular senescence. Iron\u2010overloaded BMSC in\u00a0vitro models and in\u00a0vivo murine systems were established to model osteoporosis\u2010related microenvironments. Curcumin was administered to assess its effects on cellular and systemic outcomes, including bone microstructure, mechanical property, differentiation capacity, senescence markers, iron metabolism, and redox homeostasis by using micro\u2010CT, RNA\u2010seq, RT\u2010qPCR, western blot, immunohistochemical, immunofluorescence, and transmission electron microscope (TEM). Furthermore,\n                    <jats:italic>Nrf2<\/jats:italic>\n                    siRNA and the Nrf2 inhibitor ML385 were utilized to interrogate curcumin's mechanism of action in iron\u2010overloaded BMSCs. In\u00a0vivo, curcumin treatment significantly attenuated iron overload\u2010induced bone microstructural damage, mechanical property, and elevated Nrf2 and GPX4 expression in BMSCs. In\u00a0vitro\n                    <jats:italic>,<\/jats:italic>\n                    curcumin mitigated iron overload\u2010induced ferroptosis in BMSCs by upregulating Nrf2 expression, thereby increasing GPX4 levels. This mechanism consequently delayed cellular senescence and promoted osteogenic differentiation. Our findings establish the Nrf2\/GPX4 axis as a critical therapeutic target of curcumin for ameliorating iron overload\u2010induced osteoporosis. This mechanistic insight provides a foundation for developing novel therapeutics against age\u2010related and postmenopausal osteoporosis.\n                  <\/jats:p>","DOI":"10.1002\/ptr.70346","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T07:05:48Z","timestamp":1777359948000},"page":"4188-4205","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Curcumin Alleviates the Osteogenesis Inhibition and the Aging Process in\n                    <scp>BMSCs<\/scp>\n                    Induced by Iron Overload Through Activating the\n                    <scp>NRF2<\/scp>\n                    \/\n                    <scp>GPX4<\/scp>\n                    Pathway"],"prefix":"10.1002","volume":"40","author":[{"given":"Jingmin","family":"Che","sequence":"first","affiliation":[{"name":"Shaanxi Provincial Key Laboratory of Infection and Immune Diseases Shaanxi Provincial People's Hospital  Xi'an Shaanxi China"},{"name":"Shaanxi Engineering Research Center of Cell Immunology Shaanxi Provincial People's Hospital  Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Feng","sequence":"additional","affiliation":[{"name":"Shaanxi Provincial Key Laboratory of Infection and Immune Diseases Shaanxi Provincial People's Hospital  Xi'an Shaanxi China"},{"name":"Shaanxi Engineering Research Center of Cell Immunology Shaanxi Provincial People's Hospital  Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixia","family":"Zhao","sequence":"additional","affiliation":[{"name":"Frontier Institute of Science and Technology Xi'an Jiaotong University  Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingying","family":"Sun","sequence":"additional","affiliation":[{"name":"Shaanxi Provincial Key Laboratory of Infection and Immune Diseases Shaanxi Provincial People's Hospital  Xi'an Shaanxi China"},{"name":"Shaanxi Engineering Research Center of Cell Immunology Shaanxi Provincial People's Hospital  Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihao","family":"Ren","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Northwestern Polytechnical University  Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangmeng","family":"Feng","sequence":"additional","affiliation":[{"name":"Shaanxi Provincial Key Laboratory of Infection and Immune Diseases Shaanxi Provincial People's Hospital  Xi'an Shaanxi China"},{"name":"Shaanxi Engineering Research Center of Cell Immunology Shaanxi Provincial People's Hospital  Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9498-4175","authenticated-orcid":false,"given":"Cuixiang","family":"Xu","sequence":"additional","affiliation":[{"name":"Shaanxi Provincial Key Laboratory of Infection and Immune Diseases Shaanxi Provincial People's Hospital  Xi'an Shaanxi China"},{"name":"Shaanxi Engineering Research Center of Cell Immunology Shaanxi Provincial People's Hospital  Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu\u2010Hui","family":"Li","sequence":"additional","affiliation":[{"name":"College of Forensic Medicine Xi'an Jiaotong University Health Science Center  Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,28]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2016.06.003"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2019.12.004"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12011-019-01867-4"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2024.101259"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.634650"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actaastro.2019.07.034"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2010.03.011"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/1345193"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.03.042"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2019.101107"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpt.12703"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.7326\/AITC202401160"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.maturitas.2013.05.006"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-022522-102832"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2539"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12192-020-01079-z"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.102922"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fvets.2018.00242"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12192-020-01142-9"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jot.2020.03.012"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2023.109622"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox9030205"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41413-024-00319-7"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-023-01178-1"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2023.188890"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13148"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2012.127"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.14336\/AD.2023.0510"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules191220091"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox9121228"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13018-021-02772-0"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27010167"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2015.06.006"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-020-00441-1"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/nutrit\/nuae079"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2020.02.027"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2023.154881"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-06160-w"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-024-04443-7"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12091739"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2010.05.011"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2023.166795"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2015.08.036"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41413-022-00198-w"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2024.07.024"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202404453"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1593"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.7610"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2023.01.026"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.202817"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-023-06937-x"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.111380"}],"container-title":["Phytotherapy Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ptr.70346","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ptr.70346","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ptr.70346","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T18:19:09Z","timestamp":1783448349000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ptr.70346"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,28]]},"references-count":52,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1002\/ptr.70346"],"URL":"https:\/\/doi.org\/10.1002\/ptr.70346","archive":["Portico"],"relation":{},"ISSN":["0951-418X","1099-1573"],"issn-type":[{"value":"0951-418X","type":"print"},{"value":"1099-1573","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,28]]},"assertion":[{"value":"2025-03-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}