{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T06:56:18Z","timestamp":1790751378947,"version":"4.1.0"},"reference-count":51,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271017"],"award-info":[{"award-number":["82271017"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32571424"],"award-info":[{"award-number":["32571424"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Proliferation"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Repair of maxillofacial bone defects presents significant clinical challenges. Orofacial mesenchymal stem cells (OMSCs) mediate maxillofacial bone repair, while the molecular mechanisms governing osteogenic commitment of OMSCs remain incompletely understood. Here, we investigate the function of AF4\/FMR2 family member 4 (AFF4) in OMSCs osteogenesis and maxillofacial bone healing. By using a tamoxifen\u2010inducible\n                    <jats:italic>Aff4<\/jats:italic>\n                    knockout mouse model, we demonstrate that AFF4 depletion significantly delays the alveolar bone repair post\u2010tooth extraction. OMSCs of\n                    <jats:italic>Aff4<\/jats:italic>\n                    knockout mice exhibit decreased expression of osteogenic markers (RUNX2, ALPL, OSX, COL1A1) and reduced mineralization in\u00a0vitro. Mechanistically, AFF4 loss suppresses AMPK signalling and downstream mitophagy, manifested by reduced Parkin translocation and LC3B recruitment to mitochondria, and impaired mitophagosome\u2010lysosome fusion. Notably, the rescue of mitophagy and the osteogenic capacity of\n                    <jats:italic>Aff4<\/jats:italic>\n                    \u2010deficient OMSCs by AICAR (an AMPK activator) was abolished by Compound C (an AMPK inhibitor). Collectively, our findings establish the critical role of AFF4 in maxillofacial bone regeneration and demonstrate that it functions through the AMPK\u2010mitophagy axis in OMSCs. This study provides a novel insight into the function of AFF4 in maxillofacial bone biology.\n                  <\/jats:p>","DOI":"10.1111\/cpr.70284","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T06:02:16Z","timestamp":1790748136000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>AFF4<\/scp>\n                    Loss Compromises Osteogenesis of Orofacial Mesenchymal Stem Cells During Alveolar Bone Repair via\n                    <scp>AMPK<\/scp>\n                    \u2010Mediated Mitophagy"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5325-108X","authenticated-orcid":false,"given":"Li","family":"Zhu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7426-3493","authenticated-orcid":false,"given":"Shuo","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guowen","family":"Luo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingyue","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hengyi","family":"Lin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9592-9506","authenticated-orcid":false,"given":"Yiling","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6427-5869","authenticated-orcid":false,"given":"Chenchen","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology Sichuan University  Chengdu China"},{"name":"Department of Pediatric Dentistry, West China Hospital of Stomatology Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shujuan","family":"Zou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology Sichuan University  Chengdu China"},{"name":"Department of Orthodontics, West China Hospital of Stomatology Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a025775"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.12732"},{"issue":"1","key":"e_1_2_11_4_1","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/s41368-026-00433-8","article-title":"Research Progress in Heterogeneity of Dental Mesenchymal Stem Cells","volume":"18","author":"Fu H.","year":"2026","journal-title":"International Journal of Oral Science"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41368-022-00175-3"},{"issue":"1","key":"e_1_2_11_6_1","first-page":"107","article-title":"Research Progress in Biological Characteristics and Influencing Factors of Jaw Bone Marrow Mesenchymal Stem Cell","volume":"57","author":"Li T. 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