{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T10:45:11Z","timestamp":1792147511566,"version":"4.4.0"},"reference-count":104,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"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":["Cell Biology International"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Iron overload disrupts bone homeostasis by suppressing osteoblast survival and mineralization, while promoting osteoclastogenesis. As a programmed cell death driven by iron\u2010dependent lipid peroxidation and glutathione peroxidase 4 (GPX4) downregulation. This study investigated the role of ferroptosis in bone cells under iron overload. Exposure to ferric ammonium citrate (FAC) led to decreased osteoblast viability, downregulation of GPX4 and nuclear factor erythroid 2\u2010related factor 2 (Nrf2) protein expression and osteoblastic markers. It also increased ROS production and lipid peroxidation in osteoblasts. In addition, intracellular reduced glutathione (GSH) levels showed a decreasing trend in osteoblasts exposed to FAC. Ferrostatin\u20101 (Fer\u20101), a ferroptosis inhibitor, significantly restored osteoblast viability and reduced lipid peroxidation, confirming the involvement of ferroptosis in iron\u2010induced cytotoxicity. Additionally, iron overload increased the receptor activator of nuclear factor\u2010\u03baB ligand (RANKL)\/osteoprotegerin (OPG) ratio, thereby promoting osteoclast differentiation. Interestingly, Fer\u20101 effectively attenuated these osteoclastogenic effects. On the other hand, FAC increased RAW264.7 osteoclast precursor cells viability, ROS production and lipid peroxidation; while, Fer\u20101 suppressed lipid peroxidation without affecting cell viability and ROS levels. Furthermore, we examined the role of cystine, an essential precursor for GSH synthesis and critical antioxidant cofactor for GPX4, in bone cells under iron\u2010overload conditions. Cystine enhanced osteoblast viability and reduced osteoclast viability under iron overload, but it did not exhibit a synergistic effect with Fer\u20101. These findings highlight ferroptosis as an underlying mechanism for iron\u2010induced osteoporosis and may represent a promising therapeutic strategy for managing iron overload\u2010associated bone disorders.<\/jats:p>","DOI":"10.1002\/cbin.70210","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T12:47:18Z","timestamp":1790081238000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Role of Ferroptosis Induced by Iron Overload in Osteoblast and Osteoclast Function"],"prefix":"10.1002","volume":"50","author":[{"given":"Supagarn","family":"Sooksawanwit","sequence":"first","affiliation":[{"name":"Department of Physiology, Faculty of Science Mahidol University Bangkok Thailand"},{"name":"Center of Calcium and Bone Research (COCAB), Faculty of Science Mahidol University Bangkok 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