{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T12:07:07Z","timestamp":1788264427541,"version":"build-2803163510"},"reference-count":46,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T00:00:00Z","timestamp":1753660800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T00:00:00Z","timestamp":1753660800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82072387"],"award-info":[{"award-number":["82072387"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32200943"],"award-info":[{"award-number":["32200943"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Biol"],"DOI":"10.1038\/s42003-025-08564-0","type":"journal-article","created":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T15:53:54Z","timestamp":1753718034000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Vitamin K2 inhibits PGE2-mediated osteoblast ferroptosis by upregulation of CBR1 via the Nrf2\/Keap1 pathway"],"prefix":"10.1038","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1702-9833","authenticated-orcid":false,"given":"Lin","family":"Tao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinpeng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qichang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhai","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0126-496X","authenticated-orcid":false,"given":"Yue","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,28]]},"reference":[{"key":"8564_CR1","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/S0140-6736(70)91344-9","volume":"2","author":"J Bullamore","year":"1970","unstructured":"Bullamore, J. et al. Effect of age on calcium absorption. Lancet 2, 535\u2013537 (1970).","journal-title":"Lancet"},{"key":"8564_CR2","doi-asserted-by":"crossref","unstructured":"Zhivodernikov, I. V et al. Molecular and cellular mechanisms of osteoporosis. Int. J. Mol. Sci. 24, 15772 (2023).","DOI":"10.3390\/ijms242115772"},{"key":"8564_CR3","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1186\/s12877-024-04678-y","volume":"24","author":"Z Khiyali","year":"2024","unstructured":"Khiyali, Z. et al. Smoking, alcohol consumption, drug abuse, and osteoporosis among older adults: a cross-sectional study on PERSIAN cohort study in Fasa. BMC Geriatr. 24, 80 (2024).","journal-title":"BMC Geriatr."},{"key":"8564_CR4","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1016\/S1089-3261(03)00097-7","volume":"7","author":"C Levy","year":"2003","unstructured":"Levy, C. & Lindor, K. D. Management of osteoporosis, fat-soluble vitamin deficiencies, and hyperlipidemia in primary biliary cirrhosis. Clin. Liver Dis. 7, 901\u2013910 (2003).","journal-title":"Clin. Liver Dis."},{"key":"8564_CR5","doi-asserted-by":"publisher","first-page":"Itc1","DOI":"10.7326\/AITC202401160","volume":"177","author":"KE Ensrud","year":"2024","unstructured":"Ensrud, K. E. & Crandall, C. J. Osteoporosis. Ann. Intern. Med. 177, Itc1\u2013itc16 (2024).","journal-title":"Ann. Intern. Med."},{"key":"8564_CR6","doi-asserted-by":"publisher","first-page":"186","DOI":"10.2174\/1574888X16666210512020103","volume":"17","author":"Y Liu","year":"2022","unstructured":"Liu, Y. et al. The anti-osteoporosis effects of vitamin K in postmenopausal women. Curr. Stem Cell Res Ther. 17, 186\u2013192 (2022).","journal-title":"Curr. Stem Cell Res Ther."},{"key":"8564_CR7","doi-asserted-by":"crossref","unstructured":"Wang, H., Ma, Y., The potential of vitamin K as a regulatory factor of bone metabolism-a review. Nutrients. 15, 4935 (2023).","DOI":"10.3390\/nu15234935"},{"key":"8564_CR8","first-page":"200","volume":"14","author":"MM Fusaro","year":"2017","unstructured":"Fusaro, M. M. et al. Vitamin K and bone. Clin. Cases Min. Bone Metab. 14, 200\u2013206 (2017).","journal-title":"Clin. Cases Min. Bone Metab."},{"key":"8564_CR9","doi-asserted-by":"crossref","unstructured":"Aaseth, J. O. et al. Vitamin K and calcium chelation in vascular health. Biomedicines. 11, 3154 (2023).","DOI":"10.3390\/biomedicines11123154"},{"key":"8564_CR10","first-page":"605","volume":"15","author":"M Kaneki","year":"2005","unstructured":"Kaneki, M. [Vitamin K2 as a protector of bone health and beyond]. Clin. Calcium 15, 605\u2013610 (2005).","journal-title":"Clin. Calcium"},{"key":"8564_CR11","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1007\/s00198-014-2989-6","volume":"26","author":"ZB Huang","year":"2015","unstructured":"Huang, Z. B. et al. Does vitamin K2 play a role in the prevention and treatment of osteoporosis for postmenopausal women: a meta-analysis of randomized controlled trials. Osteoporos. Int 26, 1175\u20131186 (2015).","journal-title":"Osteoporos. Int"},{"key":"8564_CR12","doi-asserted-by":"publisher","first-page":"195","DOI":"10.3143\/geriatrics.32.195","volume":"32","author":"M Kaneki","year":"1995","unstructured":"Kaneki, M. et al. [Serum concentration of vitamin K in elderly women with involutional osteoporosis]. Nihon Ronen Igakkai Zasshi 32, 195\u2013200 (1995).","journal-title":"Nihon Ronen Igakkai Zasshi"},{"key":"8564_CR13","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1038\/s41580-020-00324-8","volume":"22","author":"X Jiang","year":"2021","unstructured":"Jiang, X., Stockwell, B. R. & Conrad, M. Ferroptosis: mechanisms, biology and role in disease. Nat. Rev. Mol. Cell Biol. 22, 266\u2013282 (2021).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"8564_CR14","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1186\/s13018-023-04448-3","volume":"18","author":"Y Yang","year":"2023","unstructured":"Yang, Y. et al. Prevention and treatment of osteoporosis with natural products: Regulatory mechanism based on cell ferroptosis. J. Orthop. Surg. Res. 18, 951 (2023).","journal-title":"J. Orthop. Surg. Res."},{"key":"8564_CR15","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.986384","volume":"13","author":"Y Hu","year":"2022","unstructured":"Hu, Y. et al. Identification of ferroptosis-associated biomarkers for the potential diagnosis and treatment of postmenopausal osteoporosis. Front Endocrinol.13, 986384 (2022).","journal-title":"Front Endocrinol."},{"key":"8564_CR16","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1038\/s41586-022-05022-3","volume":"608","author":"E Mishima","year":"2022","unstructured":"Mishima, E. et al. A non-canonical vitamin K cycle is a potent ferroptosis suppressor. Nature 608, 778\u2013783 (2022).","journal-title":"Nature"},{"key":"8564_CR17","doi-asserted-by":"publisher","DOI":"10.1111\/acel.14181","volume":"23","author":"L Tao","year":"2024","unstructured":"Tao, L. et al. Exerkine FNDC5\/irisin-enriched exosomes promote proliferation and inhibit ferroptosis of osteoblasts through interaction with Caveolin-1. Aging Cell 23, e14181 (2024).","journal-title":"Aging Cell"},{"key":"8564_CR18","doi-asserted-by":"publisher","first-page":"2745","DOI":"10.1021\/acs.jafc.2c05632","volume":"71","author":"C Jin","year":"2023","unstructured":"Jin, C. et al. A Novel Anti-Osteoporosis Mechanism of VK2: Interfering with Ferroptosis via AMPK\/SIRT1 Pathway in Type 2 Diabetic Osteoporosis. J. Agric Food Chem. 71, 2745\u20132761 (2023).","journal-title":"J. Agric Food Chem."},{"key":"8564_CR19","doi-asserted-by":"crossref","unstructured":"Jiang, Z. et al. Ferroptosis in osteocytes as a target for protection against postmenopausal osteoporosis. Adv. Sci. 11, e2307388 (2024).","DOI":"10.1002\/advs.202307388"},{"key":"8564_CR20","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1302\/2046-3758.142.BJR-2023-0409.R2","volume":"14","author":"J Wang","year":"2025","unstructured":"Wang, J. et al. Development and validation of a novel prediction model for osteoporosis: from serotonin to fat-soluble vitamins. Bone Jt. Res 14, 111\u2013123 (2025).","journal-title":"Bone Jt. Res"},{"key":"8564_CR21","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202408044","volume":"11","author":"C Li","year":"2024","unstructured":"Li, C. et al. Concrete-inspired bionic bone glue repairs osteoporotic bone defects by gluing and remodeling aging macrophages. Adv. Sci.11, e2408044 (2024).","journal-title":"Adv. Sci."},{"key":"8564_CR22","doi-asserted-by":"crossref","unstructured":"Zhao, D. et al. Connexin hemichannels with prostaglandin release in anabolic function of bone to mechanical loading. Elife. 11 (2022).","DOI":"10.7554\/eLife.74365"},{"key":"8564_CR23","doi-asserted-by":"crossref","unstructured":"Saha, S., Rebouh, N. Y., Anti-osteoarthritis mechanism of the Nrf2 signaling pathway. Biomedicines. 11 (2023).","DOI":"10.3390\/biomedicines11123176"},{"key":"8564_CR24","doi-asserted-by":"crossref","unstructured":"Kajarabille, N., Latunde-Dada, G. O., Programmed cell-death by ferroptosis: antioxidants as mitigators. Int. J. Mol. Sci. 20 (2019).","DOI":"10.3390\/ijms20194968"},{"key":"8564_CR25","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.ajpath.2019.09.011","volume":"190","author":"J Qi","year":"2020","unstructured":"Qi, J. et al. Ferroptosis affects the progression of nonalcoholic steatohepatitis via the modulation of lipid peroxidation-mediated cell death in mice. Am. J. Pathol. 190, 68\u201381 (2020).","journal-title":"Am. J. Pathol."},{"key":"8564_CR26","doi-asserted-by":"crossref","unstructured":"van den Besselaar, A. et al. Defining a metrologically traceable and sustainable calibration hierarchy of international normalized ratio for monitoring of vitamin K antagonist treatment in accordance with International Organization for Standardization (ISO) 17511:2020 standard: communication from the International Federation of Clinical Chemistry and Laboratory Medicine-SSC\/ISTH working group on prothrombin time\/international normalized ratio standardization. J. Thromb. Haemost. (2023).","DOI":"10.1016\/j.jtha.2023.12.013"},{"key":"8564_CR27","doi-asserted-by":"crossref","unstructured":"Wang, H. et al. Vitamin K2 improves osteogenic differentiation by inhibiting STAT1 via the Bcl-6 and IL-6\/JAK in C3H10 T1\/2 clone 8 cells. Nutrients. 14, 2934 (2022).","DOI":"10.3390\/nu14142934"},{"key":"8564_CR28","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/2634431","volume":"2022","author":"P Liu","year":"2022","unstructured":"Liu, P. et al. Ferroptosis: a new regulatory mechanism in osteoporosis. Oxid. Med. Cell Longev. 2022, 2634431 (2022).","journal-title":"Oxid. Med. Cell Longev."},{"key":"8564_CR29","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/j.freeradbiomed.2021.04.027","volume":"169","author":"S Ni","year":"2021","unstructured":"Ni, S. et al. Hypoxia inhibits RANKL-induced ferritinophagy and protects osteoclasts from ferroptosis. Free Radic. Biol. Med. 169, 271\u2013282 (2021).","journal-title":"Free Radic. Biol. Med."},{"key":"8564_CR30","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1016\/j.cell.2012.03.042","volume":"149","author":"SJ Dixon","year":"2012","unstructured":"Dixon, S. J. et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell 149, 1060\u20131072 (2012).","journal-title":"Cell"},{"key":"8564_CR31","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2022.111836","volume":"165","author":"Z Gao","year":"2022","unstructured":"Gao, Z. et al. Ferroptosis\u2014a new target of osteoporosis. Exp. Gerontol. 165, 111836 (2022).","journal-title":"Exp. Gerontol."},{"key":"8564_CR32","doi-asserted-by":"publisher","first-page":"3760","DOI":"10.1016\/j.molcel.2022.10.001","volume":"82","author":"T Hirschhorn","year":"2022","unstructured":"Hirschhorn, T. & Stockwell, B. R. Vitamin K: a new guardian against ferroptosis. Mol. Cell 82, 3760\u20133762 (2022).","journal-title":"Mol. Cell"},{"key":"8564_CR33","doi-asserted-by":"publisher","first-page":"1240","DOI":"10.1038\/s41556-023-01237-2","volume":"25","author":"Z Wang","year":"2023","unstructured":"Wang, Z. Vitamin K inhibits ferroptosis via VKORC1L1. Nat. Cell Biol. 25, 1240 (2023).","journal-title":"Nat. Cell Biol."},{"key":"8564_CR34","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1002\/glia.24265","volume":"71","author":"L Henning","year":"2023","unstructured":"Henning, L. et al. Reactive microglia are the major source of tumor necrosis factor alpha and contribute to astrocyte dysfunction and acute seizures in experimental temporal lobe epilepsy. Glia 71, 168\u2013186 (2023).","journal-title":"Glia"},{"key":"8564_CR35","doi-asserted-by":"crossref","unstructured":"Muszy\u0144ska, M. et al. Protective effects of vitamin K compounds on the proteomic profile of osteoblasts under oxidative stress conditions. Molecules. 25, 1990 (2020).","DOI":"10.3390\/molecules25081990"},{"key":"8564_CR36","doi-asserted-by":"publisher","first-page":"11908","DOI":"10.1073\/pnas.172398899","volume":"99","author":"AT Dinkova-Kostova","year":"2002","unstructured":"Dinkova-Kostova, A. T. et al. Direct evidence that sulfhydryl groups of Keap1 are the sensors regulating induction of phase 2 enzymes that protect against carcinogens and oxidants. Proc. Natl. Acad. Sci. USA 99, 11908\u201311913 (2002).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"8564_CR37","doi-asserted-by":"publisher","first-page":"1906","DOI":"10.1089\/ars.2012.4645","volume":"18","author":"G Yang","year":"2013","unstructured":"Yang, G. et al. Hydrogen sulfide protects against cellular senescence via S-sulfhydration of Keap1 and activation of Nrf2. Antioxid. Redox Signal 18, 1906\u20131919 (2013).","journal-title":"Antioxid. Redox Signal"},{"key":"8564_CR38","doi-asserted-by":"publisher","DOI":"10.1038\/oncsis.2017.65","volume":"6","author":"Z Fan","year":"2017","unstructured":"Fan, Z. et al. Nrf2-Keap1 pathway promotes cell proliferation and diminishes ferroptosis. Oncogenesis 6, e371 (2017).","journal-title":"Oncogenesis"},{"key":"8564_CR39","doi-asserted-by":"crossref","unstructured":"Zhang, J. et al. Nrf2 and mitochondria form a mutually regulating circuit in the prevention and treatment of metabolic syndrome. Antioxid Redox Signal. 41, 744-768 (2024).","DOI":"10.1089\/ars.2023.0339"},{"key":"8564_CR40","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-1123-7","volume":"9","author":"JX Pan","year":"2018","unstructured":"Pan, J. X. et al. APP promotes osteoblast survival and bone formation by regulating mitochondrial function and preventing oxidative stress. Cell Death Dis. 9, 1077 (2018).","journal-title":"Cell Death Dis."},{"key":"8564_CR41","doi-asserted-by":"publisher","first-page":"27298","DOI":"10.1074\/jbc.M702811200","volume":"282","author":"M Almeida","year":"2007","unstructured":"Almeida, M. et al. Oxidative stress antagonizes Wnt signaling in osteoblast precursors by diverting beta-catenin from T cell factor- to forkhead box O-mediated transcription. J. Biol. Chem. 282, 27298\u201327305 (2007).","journal-title":"J. Biol. Chem."},{"key":"8564_CR42","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/9067610","volume":"2020","author":"H Ma","year":"2020","unstructured":"Ma, H. et al. Melatonin suppresses ferroptosis induced by high glucose via activation of the Nrf2\/HO-1 signaling pathway in type 2 diabetic osteoporosis. Oxid. Med. Cell Longev. 2020, 9067610 (2020).","journal-title":"Oxid. Med. Cell Longev."},{"key":"8564_CR43","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1007\/s12975-021-00912-6","volume":"12","author":"L Mao","year":"2021","unstructured":"Mao, L. et al. Carbonyl reductase 1 attenuates ischemic brain injury by reducing oxidative stress and neuroinflammation. Transl. Stroke Res. 12, 711\u2013724 (2021).","journal-title":"Transl. Stroke Res."},{"key":"8564_CR44","doi-asserted-by":"crossref","unstructured":"Kulesza, A., Paczek, L., Burdzinska, A. The role of COX-2 and PGE2 in the regulation of immunomodulation and other functions of mesenchymal stromal cells. Biomedicines. 11 (2023).","DOI":"10.3390\/biomedicines11020445"},{"key":"8564_CR45","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1002\/jcsm.13447","volume":"15","author":"D Di","year":"2024","unstructured":"Di, D. et al. Frailty phenotype as mediator between systemic inflammation and osteoporosis and fracture risks: a prospective study. J. Cachexia Sarcopenia Muscle 15, 897\u2013906 (2024).","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"8564_CR46","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1111\/febs.16609","volume":"290","author":"Y Liu","year":"2023","unstructured":"Liu, Y. et al. PGE2 pathway mediates oxidative stress-induced ferroptosis in renal tubular epithelial cells. Febs J. 290, 533\u2013549 (2023).","journal-title":"Febs J."}],"container-title":["Communications Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-08564-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-08564-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-08564-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T05:46:32Z","timestamp":1757310392000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-08564-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,28]]},"references-count":46,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["8564"],"URL":"https:\/\/doi.org\/10.1038\/s42003-025-08564-0","relation":{},"ISSN":["2399-3642"],"issn-type":[{"value":"2399-3642","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,28]]},"assertion":[{"value":"11 January 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 July 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 July 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1116"}}