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Human Stat3 deficiency triggers Hyper\u2010IgE syndrome, associated with immune dysregulation, osseous defects, and dental malformations. This study employs genetically engineered murine models to dissect Stat3's mechanistic role within mesenchymal progenitor cells during molar root formation and periodontal tissue maturation. Conditional Stat3 knockout mice (Prx1\u2010Cre; Stat3\n                    <jats:sup>f\/f<\/jats:sup>\n                    ) are generated. Comparative assessments of mandibular first molar root development between Stat3 CKO and wild\u2010type cohorts are performed through histomorphometric evaluation, micro\u2010computed tomography, cellular proliferation assays (Ki67\/BrdU), and transcriptome sequencing. Stat3 ablation causes marked morphological defects in first molars, featuring reduced root length and elevated crown\u2010root proportion. The periodontal ligament (PDL) at the distal root exhibits diminished width in mutants. Alveolar bone displays suppressed expression of osteogenic markers (Runx2, Col1a1, Ocn), accompanied by decreased Ki67\n                    <jats:sup>+<\/jats:sup>\n                    and BrdU\n                    <jats:sup>+<\/jats:sup>\n                    cell populations in the PDL. Stat3 critically regulates mandibular first molar and alveolar bone morphogenesis. Conditional ablation of Stat3 disrupts the osteogenic capacity of Prx1\n                    <jats:sup>+<\/jats:sup>\n                    mesenchymal progenitors, as evidenced across in vivo and in vitro models.\n                  <\/jats:p>","DOI":"10.1002\/adbi.202500329","type":"journal-article","created":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T14:21:33Z","timestamp":1757686893000},"source":"Crossref","is-referenced-by-count":0,"title":["Loss of Stat3 in Prx1\n                    <sup>+<\/sup>\n                    Progenitors Impairs Molar Root Development"],"prefix":"10.1002","volume":"9","author":[{"given":"Xin","family":"Feng","sequence":"first","affiliation":[{"name":"Guangdong Province Key Laboratory of Stomatology Guanghua School and Hospital of Stomatology Sun Yat\u2010sen University  Guangzhou Guangdong 510055 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wangyu","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of 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