Loss of Stat3 in Prx1+ Progenitors Impairs Molar Root Development.

IF 2.6 3区 生物学 Q3 MATERIALS SCIENCE, BIOMATERIALS
Xin Feng, Wangyu Luo, Yichen Yao, Lichieh Lin, Laiting Chan, Jiarui Lu, Zijing Huang, Jingyi Feng, Le Zhao, Xiaolei Zhang, Liu Yang
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Abstract

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.

Prx1+祖细胞中Stat3的缺失会损害臼齿根的发育。
信号转导和转录激活因子3 (Stat3)作为中枢转录调节剂协调细胞增殖、存活、凋亡、血管形成、免疫调节和迁移过程。人类Stat3缺乏会引发高ige综合征,与免疫失调、骨缺损和牙齿畸形相关。本研究采用基因工程小鼠模型来分析Stat3在磨牙根形成和牙周组织成熟过程中在间充质祖细胞中的机制作用。生成条件Stat3敲除小鼠(Prx1-Cre; Stat3f/f)。通过组织形态学评估、显微计算机断层扫描、细胞增殖测定(Ki67/BrdU)和转录组测序,对Stat3 CKO和野生型队列的下颌第一磨牙根发育进行了比较评估。Stat3消融导致第一磨牙明显的形态缺损,表现为牙根长度缩短,冠根比例升高。在突变体中,远端根的牙周韧带(PDL)宽度减小。牙槽骨显示成骨标志物(Runx2, Col1a1, Ocn)的表达受到抑制,同时PDL中Ki67+和BrdU+细胞数量减少。Stat3对下颌第一磨牙和牙槽骨形态发生有重要的调控作用。在体内和体外模型中证实,Stat3的条件消融会破坏Prx1+间充质祖细胞的成骨能力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Advanced biology
Advanced biology Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)
CiteScore
6.60
自引率
0.00%
发文量
130
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