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In this study, it is found that senescent bone marrow mesenchymal stem cells (BMSCs) exhibit increased sensitivity to ferroptosis, a phenomenon associated with Steap4, a nicotinamide adenine dinucleotide phosphate hydrogen (NADPH)\u2010dependent metalloreductase that reduces Fe\n                    <jats:sup>3+<\/jats:sup>\n                    to Fe\n                    <jats:sup>2+<\/jats:sup>\n                    . Therefore, it is aimed to innovatively elucidate how Steap4 affects ferroptosis in senescent BMSCs. These findings indicate that Steap4 promotes intracellular Fe\n                    <jats:sup>2+<\/jats:sup>\n                    accumulation and elevates reactive oxygen species (ROS) levels, collectively driving the upregulation of CCAAT\/enhancer binding protein beta (C\/EBP\u03b2) expression. Interestingly, a functional C\/EBP\u03b2 binding site is identified within the Steap4 promoter region. Mechanistically, knockdown studies demonstrated that C\/EBP\u03b2 depletion attenuated Steap4 expression, whereas C\/EBP\u03b2 overexpression conversely upregulated Steap4 levels. These regulatory processes establish a self\u2010amplifying Steap4\/Fe\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010ROS\/C\/EBP\u03b2 positive feedback loop. Notably, a large number of adipocytes are also observed in the bone marrow of aged mice. Knockdown of Steap4 and C\/EBP\u03b2 suppressed the differentiation of BMSCs into adipocytes. Knockdown of Steap4 or deferoxamine (DFO) treatment in animal experiments effectively relieves SOP. In conclusion, Steap4 accelerates the onset of ferroptosis in senescent BMSCs and promotes their differentiation to adipocytes through the Steap4\/Fe\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010ROS\/C\/EBP\u03b2 axis, ultimately impairing their osteogenic capacity.\n                  <\/jats:p>","DOI":"10.1002\/advs.202509926","type":"journal-article","created":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T12:05:15Z","timestamp":1762517115000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Steap4 Promotes Senile Osteoporosis via Fe\n                    <sup>2+<\/sup>\n                    \u2010ROS\/C\/EBP\u03b2 Feedback\u2010Driven Ferroptosis and Adipogenesis in Senescent BMSCs"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-4137-1532","authenticated-orcid":false,"given":"Liangliang","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Orthopaedics the Second People's Hospital of Changzhou the Third Affiliated Hospital of Nanjing Medical University Changzhou Medical Center Nanjing Medical University  Changzhou 213003 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangrong","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics the Second People's Hospital of Changzhou the Third Affiliated Hospital of Nanjing Medical University Changzhou Medical Center Nanjing Medical University  Changzhou 213003 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenming","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics The First Affiliated Hospital of Soochow University  Suzhou 215006 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