Constitutive stabilization of β-catenin in the dental mesenchyme leads to excessive dentin and cementum formation
Constitutive stabilization of β-catenin in the dental mesenchyme leads to excessive dentin and cementum formation
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DOI：
10.1016/j.bbrc.2011.07.116
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发表时间：
2011-09-09
影响因子：
3.1
通讯作者：
Cho, Eui-Sic
中科院分区：
文献类型：
--
作者：
Kim, Tak-Heun;Lee, Ju-Yeon;Cho, Eui-Sic
Wnt/β-catenin信号在发育过程中的形态发生和细胞分化中起重要作用。Wnt/β-catenin信号在牙齿形态发生中的重要作用已为人们所熟知，但Wnt/β-catenin信号在牙齿硬组织形成中的作用尚不明确。为了了解Wnt/β-catenin信号在牙本质和牙骨质形成中的作用，我们在牙本质间充质中建立并分析了条件性β-catenin稳定的小鼠。OC-Cre；Catnb(lox(Ex3)/+)小鼠表现出畸形的牙齿，其特征是牙本质异常形成和牙骨质过度沉积。大量牙本质迅速形成，前牙本质变宽，牙冠内有大量球状钙化。磨牙根部较短，被过度形成的细胞牙骨质覆盖。随着年龄增长，牙髓腔和牙周间隙分别因过度形成的牙本质和牙骨质而变窄。为了比较突变小鼠基因表达的变化，在成牙本质细胞中，Col1a1的表达增加，而Dspp的表达降低。而成牙骨质细胞中Cal1a1和BSP的表达均增加。基因表达的变化与基质蛋白的定位一致。Biglycan和PC-1分别在成牙本质细胞和牙本质基质中表达增加，而PHEX表达降低。成牙骨质细胞和牙骨质基质中TnAP升高，Dmp1和FGF23降低。我们的结果表明，g-catenin在牙间充质中的持续稳定导致成牙本质细胞的过早分化和成牙骨质细胞的分化，并在体内诱导过多的牙本质和牙骨质形成。这些结果表明，Wnt/β-catenin信号在成牙本质细胞和成牙骨质细胞分化过程中起着重要的时空调控作用，抑制Wnt/β-catenin信号可能在牙齿发育过程中牙本质和牙骨质的形成中起重要作用。局部调控Wnt/β-catenin信号转导系统具有促进牙本质和牙周组织再生的治疗潜力。(C)2011 Elsevier Inc.保留所有权利。
Wnt/beta-catenin signaling plays an important role in morphogenesis and cellular differentiation during development. Essential roles of Wnt/beta-catenin signaling in tooth morphogenesis have been well known, but the involvement of Wnt/beta-catenin signaling in the dental hard tissue formation remains undefined. To understand roles of Wnt/beta-catenin signaling in dentin and cementum formation, we generated and analyzed the conditional beta-catenin stabilized mice in the dental mesenchyme. The OC-Cre;Catnb(lox(ex3)/+) mice exhibited malformed teeth characterized by aberrantly formed dentin and excessively deposited cementum. Large amount of dentin was rapidly formed with widened predentin and numerous globular calcifications in the crown. Whereas roots of molars were short and covered with the excessively formed cellular cementum. With age, the coronal pulp chamber and periodontal space were narrowed by the excessively formed dentin and cementum, respectively. To compare the changes of gene expression in the mutant mice, Col1a1 expression was increased but that of Dspp was decreased in the odontoblasts. However, both of Cal1a1 and Bsp expression was increased in the cementoblasts. The gene expression changes were consistent with the localization of matrix proteins. Biglycan and PC-1 was increased but Phex was decreased in the odontoblasts and dentin matrix, respectively. TNAP was increased but Dmp1 and FGF23 was decreased in the cementoblasts and cementum matrix, respectively. Our results indicate that persistent stabilization of g-catenin in the dental mesenchyme leads to premature differentiation of odontoblasts and differentiation of cementoblasts, and induces excessive dentin and cementum formation in vivo. These results suggest that temporospatial regulation of Wnt/beta-catenin signaling plays critical roles in the differentiation of odontoblasts and cementoblasts, and that inhibition of Wnt/beta-catenin signaling may be important for the formation of dentin and cementum during tooth development. Local modulation of Wnt/beta-catenin signaling has therapeutic potential to improve the regeneration of dentin and periodontium. (C) 2011 Elsevier Inc. All rights reserved.