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Bone marrow mesenchymal stem cells (BMSCs) give rise to bone marrow adipocytes. The transcription factor interferon regulatory factor 1 (IRF1) modulates multiple biological processes, including the adipogenesis of several cell types. However, the role of IRF1 in the commitment of BMSCs to the adipogenic lineage and whether it regulates bone marrow adipogenesis has not been investigated thoroughly. Murine BMSCs (mBMSCs) with\n                    <jats:italic>Irf1<\/jats:italic>\n                    \u2010overexpression or knockdown were established via lentiviral transfection. IRF1's effects on adipogenic differentiation and autophagy of mBMSCs were studied in\u00a0vitro; its role in adipogenesis in\u00a0vivo was evaluated via nude mouse subcutaneous transplantation.\n                    <jats:italic>Irf1<\/jats:italic>\n                    \u2010overexpressing mBMSCs were intravenously injected into OVX and aged osteoporotic mice. Besides, RNA sequencing and experimental verification explored the mechanism. IRF1 inhibited the adipogenic differentiation of mBMSCs both in\u00a0vitro and in\u00a0vivo. Besides, IRF1 positively regulated autophagy in mBMSCs in\u00a0vitro. In osteoporotic mice, injection of\n                    <jats:italic>Irf1<\/jats:italic>\n                    \u2010overexpressing mBMSCs effectively decreased bone marrow adiposity. IRF1 may downregulate adipogenic differentiation of mBMSCs by regulating the 5\u2032\u2010adenosine monophosphate (AMP)\u2010activated protein kinase (AMPK)\u2010mammalian target of rapamycin (mTOR) signaling axis. This study reveals that IRF1 induces protective autophagy and inhibits adipogenic differentiation of mBMSCs.\n                    <jats:italic>Irf1<\/jats:italic>\n                    \u2010overexpressing mBMSCs alleviate osteoporosis\u2010related bone marrow adiposity. Besides, IRF1 possibly regulates the AMPK\u2013mTOR signaling axis. Our findings establish IRF1 as a key factor inhibiting adipogenesis, providing a new potential therapeutic target for preventing and treating osteoporosis\u2010related bone marrow adiposity and other diseases with abnormal adipose metabolism.\n                  <\/jats:p>","DOI":"10.1096\/fj.202601902rr","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T14:31:29Z","timestamp":1789655489000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Interferon Regulatory Factor 1 Inhibits the Adipogenic Differentiation of\n                    <scp>BMSCs<\/scp>\n                    via the\n                    <scp>AMPK<\/scp>\n                    \u2013\n                    <scp>mTOR<\/scp>\n                    Signaling Axis and Induces Their Autophagy to Alleviate Osteoporosis\u2010Related Bone Marrow Adiposity"],"prefix":"10.1096","volume":"40","author":[{"given":"Menglong","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Prosthodontics Peking University School and Hospital of Stomatology &amp; National Center for Stomatology &amp; National Clinical Research Center for Oral Diseases &amp; National Engineering Research Center of Oral Biomaterials and Digital Medical Devices &amp; Beijing Key Laboratory of Digital Stomatology &amp; NHC Key Laboratory of Digital Stomatology &amp; NMPA Key Laboratory for Dental Materials  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erfan","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Prosthodontics Peking University School and Hospital of Stomatology &amp; National Center for Stomatology &amp; National Clinical Research Center for Oral Diseases &amp; National Engineering Research Center of Oral Biomaterials and Digital Medical Devices &amp; Beijing Key Laboratory of Digital Stomatology &amp; NHC Key Laboratory of Digital Stomatology &amp; NMPA Key Laboratory for Dental Materials  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Likun","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Prosthodontics Peking University School and Hospital of Stomatology &amp; National Center for Stomatology &amp; National Clinical Research Center for Oral Diseases &amp; National Engineering Research Center of Oral Biomaterials and Digital Medical Devices &amp; Beijing Key Laboratory of Digital Stomatology &amp; NHC Key Laboratory of Digital Stomatology &amp; NMPA Key Laboratory for Dental Materials  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingtong","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Prosthodontics Peking University School and Hospital of Stomatology &amp; National Center for Stomatology &amp; National Clinical Research Center for Oral Diseases &amp; National Engineering Research Center of Oral Biomaterials and Digital Medical Devices &amp; Beijing Key Laboratory of Digital Stomatology &amp; NHC Key Laboratory of Digital Stomatology &amp; NMPA Key Laboratory for Dental Materials  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiyue","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Prosthodontics Peking University School and Hospital of Stomatology &amp; National Center for Stomatology &amp; National Clinical Research Center for Oral Diseases &amp; National Engineering Research Center of Oral Biomaterials and Digital Medical Devices &amp; Beijing Key Laboratory of Digital Stomatology &amp; NHC Key Laboratory of Digital Stomatology &amp; NMPA Key Laboratory for Dental Materials  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuyun","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Prosthodontics Peking University School and Hospital of Stomatology &amp; National Center for Stomatology &amp; National Clinical Research Center for Oral Diseases &amp; National Engineering Research Center of Oral Biomaterials and Digital Medical Devices &amp; Beijing Key Laboratory of Digital Stomatology &amp; NHC Key Laboratory of Digital Stomatology &amp; NMPA Key Laboratory for Dental Materials  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"Dong","sequence":"additional","affiliation":[{"name":"Central Laboratory Peking University School and Hospital of Stomatology &amp; 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