{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T07:01:16Z","timestamp":1790319676107,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["xzy012025148"],"award-info":[{"award-number":["xzy012025148"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"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"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Pineal Research"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Postmenopausal osteoporosis (PMOP) is linked to iron accumulation. Melatonin has iron\u2010chelating and antioxidant properties, but its mechanism against osteoclastogenesis remains unclear. This study investigated whether melatonin suppresses osteoclast formation by targeting the iron\/ROS\u2010CREB\u2010PGC\u20101\u03b2\u2010mediated mitochondrial biogenesis pathway.\n                    <jats:italic>In vitro<\/jats:italic>\n                    , bone marrow\u2010derived macrophages (BMMs) were treated with RANKL and melatonin (10\u20131000\u2009nM). Melatonin concentration\u2010dependently inhibited osteoclast differentiation, reduced intracellular ferrous and total iron levels, decreased ROS and oxidative stress markers, and suppressed mitochondrial biogenesis. Mechanistically, melatonin indirectly suppressed PGC\u20111\u03b2 expression via inhibition of CREB phosphorylation, without affecting PGC\u20111\u03b1 expression. The CREB activator forskolin reversed melatonin's effects, whereas the CREB inhibitor 666\u201015 mimicked them.\n                    <jats:italic>In vivo<\/jats:italic>\n                    , ovariectomized (OVX) mice received weekly injections of iron dextran to model moderate iron overload, with or without oral melatonin. Melatonin ameliorated iron\u2011induced bone loss, improved bone microarchitecture and biomechanical properties, reduced tissue iron stores and bone ROS levels, and suppressed osteoclast mitochondrial biogenesis and the CREB\/PGC\u20101\u03b2 pathway; these effects were counteracted by forskolin. In conclusion, melatonin prevents osteoclastogenesis and counters bone loss due to iron accumulation in estrogen\u2011deficient conditions by chelating iron, scavenging ROS, and blocking the iron\/ROS\u2011activated CREB\/PGC\u20111\u03b2 axis, thereby suppressing mitochondrial biogenesis. This study offers a mechanistic explanation for using melatonin as a possible treatment for PMOP, particularly when accompanied by iron overload.\n                  <\/jats:p>","DOI":"10.1111\/jpi.70182","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T10:20:15Z","timestamp":1786357215000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Melatonin Suppresses Osteoclastogenesis via Inhibiting Iron\/ROS\u2010CREB\/PGC\u20101\u03b2\u2010Mediated Mitochondrial Biogenesis"],"prefix":"10.1111","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0008-9036","authenticated-orcid":false,"given":"Jiancheng","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Osteoporosis, Honghui Hospital Xi'an Jiaotong University Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4006-6384","authenticated-orcid":false,"given":"Jingmin","family":"Che","sequence":"additional","affiliation":[{"name":"Shaanxi Provincial Key Laboratory of Infection and Immune Diseases Shaanxi Provincial People's Hospital Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Osteoporosis, Honghui Hospital Xi'an Jiaotong University Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Osteoporosis, Honghui Hospital Xi'an Jiaotong University Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingmei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Osteoporosis, Honghui Hospital Xi'an Jiaotong University Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhong","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Osteoporosis, Honghui Hospital Xi'an Jiaotong University Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11657-025-01539-y"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2021.21106"},{"key":"e_1_2_9_4_1","first-page":"132","article-title":"Ovarian Aging: The Silent Catalyst of Age\u2010Related Disorders in Female Body","volume":"17","author":"Liu X.","year":"2026","journal-title":"Aging and disease"},{"key":"e_1_2_9_5_1","first-page":"849","article-title":"\u201cMetabolic Rewiring and Post\u2010Translational Modifications: Unlocking the Mechanisms of Bone Turnover in Osteoporosis","volume":"17","author":"Li Y.","year":"2026","journal-title":"Aging and Disease"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcp2307353"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jot.2024.10.012"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41413-023-00247-y"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.34133\/bmef.0230"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202307388"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-024-00730-2"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10565-023-09834-5"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.645140"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.111380"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2022.101717"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.70062"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11914-023-00825-3"},{"key":"e_1_2_9_18_1","first-page":"1784","article-title":"\u201cThe Emerging Role of the Mitochondrial Respiratory Chain in Skeletal Aging","volume":"15","author":"Tao H.","year":"2024","journal-title":"Aging and Disease"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.34133\/research.0840"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-019-00757-0"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1910"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41421-025-00853-6"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.478750"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2024.111135"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-024-07261-8"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.141"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.magmed.2025.100051"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jot.2022.10.007"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202402646R"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1631\/jzus.B2200519"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11596-023-2764-z"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.961903"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-12-260083"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-043021-032816"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23073593"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/iub.2928"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-025-05802-w"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.202817"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1515"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12782"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12252"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.70055"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2002.17.7.1219"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.17440"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12465"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms150917130"}],"container-title":["Journal of Pineal Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jpi.70182","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jpi.70182","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jpi.70182","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T06:48:17Z","timestamp":1790318897000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jpi.70182"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,10]]},"references-count":45,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1111\/jpi.70182"],"URL":"https:\/\/doi.org\/10.1111\/jpi.70182","archive":["Portico"],"relation":{},"ISSN":["0742-3098","1600-079X"],"issn-type":[{"value":"0742-3098","type":"print"},{"value":"1600-079X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,10]]},"assertion":[{"value":"2026-05-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70182"}}