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Ovariectomized (OVX) rats received IFN\u2010\u03b3 (5000\u2009IU\/dose, 3\u00d7\/week for 24\u2009weeks), with jawbone mass assessed via micro\u2010CT and HE staining. JBMSCs were cultured, and osteogenic differentiation under IFN\u2010\u03b3 (optimal concentration: 10\u2009ng\/mL) was evaluated using qRT\u2010PCR, ALP\/alizarin red staining, and CCK\u20108. METTL3's role was analyzed via lentiviral overexpression (OE\u2010METTL3) or knockdown (sh\u2010METTL3). JAK2\/STAT3 pathway activity was tested using AG490 (JAK2 inhibitor) and Western blot for phosphorylated JAK2\/STAT3. IFN\u2010\u03b3 reduced alveolar bone loss in OVX rats, increased osteocytes, and decreased osteoclasts. In JBMSCs, 10\u2009ng\/mL IFN\u2010\u03b3 upregulated osteogenic genes (Runx2, OPN, OPG) and mineralization. METTL3 expression was elevated by IFN\u2010\u03b3; sh\u2010METTL3 suppressed Runx2, while OE\u2010METTL3 reversed OVX\u2010induced osteogenic inhibition. IFN\u2010\u03b3 activated JAK2\/STAT3 signaling, but AG490 reduced both osteogenic gene expression and METTL3 levels. METTL3 overexpression amplified JAK2\/STAT3 phosphorylation, synergizing with IFN\u2010\u03b3 to enhance osteogenesis. IFN\u2010\u03b3 activates the JAK2\/STAT3 pathway to drive METTL3 transcription, upregulating osteogenic genes and mitigating jawbone loss in POP. METTL3 overexpression counteracts estrogen deficiency\u2010induced osteogenic suppression and forms a positive feedback loop with JAK2\/STAT3. AG490's complete blockade of IFN\u2010\u03b3\/METTL3 effects confirms the JAK2\/STAT3\u2010METTL3 axis as central to bone immune metabolism, highlighting therapeutic potential for targeting this pathway in POP.<\/jats:p>","DOI":"10.1096\/fj.202500931r","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T15:26:40Z","timestamp":1756826800000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["<scp>IFN<\/scp>\n                    \u2010\u03b3 Targeting the\n                    <scp>JAK2<\/scp>\n                    \/\n                    <scp>STAT3<\/scp>\n                    \u2010\n                    <scp>METTL3<\/scp>\n                    Pathway Ameliorates Mandibular Osteogenic Differentiation in Postmenopausal Rats"],"prefix":"10.1096","volume":"39","author":[{"given":"Shan\u2010shan","family":"Yang","sequence":"first","affiliation":[{"name":"School and Hospital of Stomatology 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