{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T17:19:31Z","timestamp":1786123171085,"version":"build-2736575974"},"reference-count":38,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"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":["The Kaohsiung J of Med Scie"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The prevalence of postmenopausal osteoporosis (PMOP) has been steadily increasing. Ferroptosis has been recognized as a critical factor influencing the bone\u2010forming ability of bone marrow mesenchymal stem cells (BMSCs). Valproic acid (VPA), an HDAC inhibitor, has been suggested to play a role in regulating osteoporosis development; however, its underlying mechanism remains unclear. This study aims to explore the impact of VPA on ferroptosis, a process that is triggered by Erastin, and to assess its implications for postmenopausal osteoporosis (PMOP). We evaluated the effects of valproate sodium on Erastin\u2010induced ferroptosis in BMSCs through in\u00a0vitro experiments, including CCK\u20108 assays, Western blot analysis, mitochondrial function assessments (MDA, GSH, ROS, and MMP), and osteogenic evaluations (ALP and ARS staining). The impact of VPA on bone integration in ovariectomized (OVX) rats was assessed using micro\u2010CT, hematoxylin\u2013eosin (HE) staining, Masson's trichrome staining, and RT\u2010PCR analysis. RNA sequencing was employed to investigate the underlying mechanisms of VPA action. Our findings demonstrate that VPA treatment prevents the Erastin\u2010induced decline in the osteogenic capacity of BMSCs. In addition, VPA treatment suppresses ferroptosis, as indicated by decreased malondialdehyde levels, reduced mitochondrial ROS, and increased glutathione concentrations. Moreover, VPA treatment promotes trabecular bone growth and enhances bone integration. Mechanistic studies reveal that SIRT1\u2013siRNA counteracts the beneficial effects of VPA in Erastin\u2010treated BMSCs. VPA improves bone integration in OVX rats by activating the AMPK\/SIRT1 pathway and inhibiting ferroptosis.<\/jats:p>","DOI":"10.1002\/kjm2.70175","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T10:28:24Z","timestamp":1770200904000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Valproic Acid Inhibits Ferroptosis and Improves Bone Integration in\n                    <scp>OVX<\/scp>\n                    Rats Through the\n                    <scp>AMPK<\/scp>\n                    \/\n                    <scp>SIRT1<\/scp>\n                    Pathway"],"prefix":"10.1002","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-4344-3003","authenticated-orcid":false,"given":"Qing\u2010Song","family":"Gu","sequence":"first","affiliation":[{"name":"Department of Trauma Orthopedics The First Affiliated Hospital of Wannan Medical College, Yijishan Hospital  Wuhu Anhui People's 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