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In the present study, we found that SA treatment promoted the accumulation of iron, Fe<jats:sup>2+<\/jats:sup>, lipid peroxide, and malondialdehyde, increased TFRC and reduced FTH1 and GPX4 to trigger ferroptosis in rat bone marrow mesenchymal stem cells (BMSCs).\u00a0Interestingly, increased level of N6 methyl adenosine (m6A) modification along with decreased expression level of m6A eraser FTO were observed in SA\u2010induced BMSCs, while upregulating FTO alleviated SA\u2010triggered ferroptosis and protected cell viability in BMSCs. Mechanistically, MDM2 was identified as a target of FTO\u2010mediated m6A demethylation, and FTO upregulation\u00a0promoted MDM2 instability to downregulated TLR4 signal and elevate the expression of SLC7A11 and GPX4 in SA\u2010induced BMSCs. Functional recovery experiments verified that overexpressing MDM2 or TLR4 reversed the inhibiting effect of FTO upregulation on ferroptosis in SA\u2010treated BMSCs. Additionally, FTO upregulation restrained ferroptosis and pathological damage to bone tissue in SA\u2010induced osteomyelitis model rats. Altogether, m6A eraser FTO alleviates SA\u2010induced ferroptosis in osteomyelitis models partly through inhibiting the MDM2\u2010TLR4\u00a0axis.<\/jats:p>","DOI":"10.1002\/cbin.12115","type":"journal-article","created":{"date-parts":[[2024,1,2]],"date-time":"2024-01-02T20:29:56Z","timestamp":1704227396000},"page":"450-460","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["N6 methyladenosine eraser FTO suppresses <i>Staphylococcus aureus<\/i>\u2010induced ferroptosis of bone marrow mesenchymal stem cells to ameliorate osteomyelitis through regulating the MDM2\/TLR4\/SLC7A11 signaling pathway"],"prefix":"10.1002","volume":"48","author":[{"given":"Muguo","family":"Song","sequence":"first","affiliation":[{"name":"Graduate School of Kunming Medical University Kunming China"},{"name":"Orthopaedics Department 920th Hospital of Joint Logistics Support Force Kunming 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