Xin Feng, Wangyu Luo, Yichen Yao, Lichieh Lin, Laiting Chan, Jiarui Lu, Zijing Huang, Jingyi Feng, Le Zhao, Xiaolei Zhang, Liu Yang
{"title":"Prx1+祖细胞中Stat3的缺失会损害臼齿根的发育。","authors":"Xin Feng, Wangyu Luo, Yichen Yao, Lichieh Lin, Laiting Chan, Jiarui Lu, Zijing Huang, Jingyi Feng, Le Zhao, Xiaolei Zhang, Liu Yang","doi":"10.1002/adbi.202500329","DOIUrl":null,"url":null,"abstract":"<p><p>Signal Transducer and Activator of Transcription 3 (Stat3) acts as a central transcriptional modulator coordinating cellular proliferation, survival, apoptosis, vascularization, immune regulation, and migratory processes. Human Stat3 deficiency triggers Hyper-IgE 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-Cre; Stat3<sup>f/f</sup>) are generated. Comparative assessments of mandibular first molar root development between Stat3 CKO and wild-type cohorts are performed through histomorphometric evaluation, micro-computed 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-root 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<sup>+</sup> and BrdU<sup>+</sup> 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<sup>+</sup> mesenchymal progenitors, as evidenced across in vivo and in vitro models.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":" ","pages":"e00329"},"PeriodicalIF":2.6000,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Loss of Stat3 in Prx1<sup>+</sup> Progenitors Impairs Molar Root Development.\",\"authors\":\"Xin Feng, Wangyu Luo, Yichen Yao, Lichieh Lin, Laiting Chan, Jiarui Lu, Zijing Huang, Jingyi Feng, Le Zhao, Xiaolei Zhang, Liu Yang\",\"doi\":\"10.1002/adbi.202500329\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Signal Transducer and Activator of Transcription 3 (Stat3) acts as a central transcriptional modulator coordinating cellular proliferation, survival, apoptosis, vascularization, immune regulation, and migratory processes. Human Stat3 deficiency triggers Hyper-IgE 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-Cre; Stat3<sup>f/f</sup>) are generated. Comparative assessments of mandibular first molar root development between Stat3 CKO and wild-type cohorts are performed through histomorphometric evaluation, micro-computed 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-root 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<sup>+</sup> and BrdU<sup>+</sup> 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<sup>+</sup> mesenchymal progenitors, as evidenced across in vivo and in vitro models.</p>\",\"PeriodicalId\":7234,\"journal\":{\"name\":\"Advanced biology\",\"volume\":\" \",\"pages\":\"e00329\"},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2025-09-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Advanced biology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1002/adbi.202500329\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"MATERIALS SCIENCE, BIOMATERIALS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advanced biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1002/adbi.202500329","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MATERIALS SCIENCE, BIOMATERIALS","Score":null,"Total":0}
Loss of Stat3 in Prx1+ Progenitors Impairs Molar Root Development.
Signal Transducer and Activator of Transcription 3 (Stat3) acts as a central transcriptional modulator coordinating cellular proliferation, survival, apoptosis, vascularization, immune regulation, and migratory processes. Human Stat3 deficiency triggers Hyper-IgE 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-Cre; Stat3f/f) are generated. Comparative assessments of mandibular first molar root development between Stat3 CKO and wild-type cohorts are performed through histomorphometric evaluation, micro-computed 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-root 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+ and BrdU+ 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+ mesenchymal progenitors, as evidenced across in vivo and in vitro models.