{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T17:03:37Z","timestamp":1782320617099,"version":"3.54.5"},"reference-count":38,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100017531","name":"Medical and Health Research Project of Zhejiang Province","doi-asserted-by":"publisher","award":["2023RC213"],"award-info":[{"award-number":["2023RC213"]}],"id":[{"id":"10.13039\/501100017531","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2026,6,30]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Glucocorticoid\u2010induced osteonecrosis of the femoral head (GIONFH) is a frequently encountered complication in orthopedic practice, yet its precise pathogenic mechanisms remain incompletely understood. Dysregulation of bone metabolism induced by glucocorticoids (GCs) is considered a key contributing factor. 3,4\u2010Dimethoxychalcone (3,4DC), an organic compound, has shown potential biological activities, but its role in the context of GIONFH has not been elucidated. This study investigates the protective effects and underlying mechanisms of 3,4DC against dexamethasone (Dex)\u2010induced ferroptosis and its therapeutic potential in GIONFH.A rat model of GIONFH was established through intraperitoneal administration of Dex, and in\u00a0vitro studies were performed by culturing osteoblasts (OBs) under Dex treatment conditions. To evaluate the effects of 3,4DC on Dex\u2010treated OBs, we employed C11\u2010BODIPY and FerroOrange staining, assessed mitochondrial function, and analyzed protein expression via Western blot and immunofluorescence. The impact of 3,4DC on the bone microarchitecture of the femoral head in rats was further examined using micro\u2010CT, H&amp;E staining, as well as immunofluorescence and immunohistochemistry at both imaging and histological levels. Our results indicate that 3,4DC effectively inhibits Dex\u2010induced ferroptosis and attenuates the development of GIONFH. In\u00a0vitro, 3,4DC treatment significantly increased glutathione (GSH) levels while reducing malondialdehyde (MDA) production, lipid peroxidation, and mitochondrial reactive oxygen species (ROS) accumulation. Furthermore, 3,4DC enhanced STAT3 phosphorylation, upregulated glutathione peroxidase 4 (GPX4) and osteogenesis\u2010related proteins, and promoted bone formation. Mechanistically, 3,4DC activated the STAT3\/Nrf2 signaling pathway. Notably, silencing STAT3 with siRNA abrogated the protective effects of 3,4DC in Dex\u2010treated OBs.3,4DC alleviates GIONFH by activating the STAT3\/Nrf2 signaling pathway, thereby suppressing ferroptosis and may have potential clinical applications.<\/jats:p>","DOI":"10.1096\/fj.202600307r","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:42:01Z","timestamp":1781106121000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["3,4\u2010Dimethoxychalcone Protects Against Steroid Induced Femoral Head Necrosis by Suppressing Ferroptosis via Activation of\n                    <scp>STAT3<\/scp>\n                    \u2010Nrf2 Signaling Pathway"],"prefix":"10.1096","volume":"40","author":[{"given":"Li\u2010jiang","family":"Han","sequence":"first","affiliation":[{"name":"Department of Orthopaedic The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical 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Zhejiang Province  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guang\u2010can","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"Key Laboratory of Orthopaedics of Zhejiang Province  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian\u2010feng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"Key Laboratory of Orthopaedics of Zhejiang Province  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lian\u2010wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical 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