Distinctive role of ACVR1 in dentin formation: requirement for dentin thickness in molars and prevention of osteodentin formation in incisors of mice
Distinctive role of ACVR1 in dentin formation: requirement for dentin thickness in molars and prevention of osteodentin formation in incisors of mice
复制标题
ACVR1在牙本质形成中的独特作用：磨牙牙本质厚度的要求和预防小鼠门牙骨牙本质形成
DOI：
10.1007/s10735-018-9806-z
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发表时间：
2019
影响因子：
3.2
通讯作者：
Sun Hongchen
中科院分区：
文献类型：
--
作者：
Zhang Xue;Shi Ce;Zhao Huan;Zhou Yijun;Hu Yue;Yan Guangxing;Liu Cangwei;Li Daowei;Hao Xinqing;Mishina Yuji;Liu Qilin;Sun Hongchen
牙本质是牙齿的主要组成部分，具有保护牙髓和维持牙齿健康的作用。骨形态发生蛋白（BMP）信号传导是牙本质形成所必需的。在神经嵴中缺乏BMP I型受体，激活素A受体1（ACVR 1）的小鼠表现出畸形的下颌骨。然而，关于ACVR 1介导的BMP信号如何调节牙本质形成知之甚少。为了探索ACVR 1在小鼠磨牙和切牙牙本质形成中的作用，在Osterix表达细胞中条件性破坏Acvr 1（命名为cKO）。我们发现牙间充质中Acvr 1的缺失导致磨牙的牙本质发育不良和切牙的骨牙本质形成。具体而言，cKO小鼠表现出显着的牙齿表型，其特征在于较薄的牙本质和较厚的前牙本质，以及磨牙中成牙本质细胞的分化受损。我们还发现，在cKO下颌切牙的冠状部分，这是与成牙基因Dsp的表达减少和成骨基因Bsp的表达增加，导致从成牙本质细胞成骨细胞的细胞命运的改变。此外，与相应的对照组相比，cKO切牙中WNT拮抗剂Dkk 1和Sost的表达下调，而B-catenin的表达上调，而cKO磨牙中的表达水平没有变化。我们的研究结果表明ACVR 1在切牙和磨牙之间的独特和关键作用，这与WNT信号相关分子的改变有关。这项研究首次证明了ACVR 1在牙本质形成过程中的生理作用。
Dentin is a major component of teeth that protects dental pulp and maintains tooth health. Bone morphogenetic protein (BMP) signaling is required for the formation of dentin. Mice lacking a BMP type I receptor, activin A receptor type 1 (ACVR1), in the neural crest display a deformed mandible.Acvr1is known to be expressed in the dental mesenchyme. However, little is known about how BMP signaling mediated by ACVR1 regulates dentinogenesis. To explore the role of ACVR1 in dentin formation in molars and incisors in mice,Acvr1was conditionally disrupted inOsterix-expressing cells (designated as cKO). We found that loss ofAcvr1in the dental mesenchyme led to dentin dysplasia in molars and osteodentin formation in incisors. Specifically, the cKO mice exhibited remarkable tooth phenotypes characterized by thinner dentin and thicker predentin, as well as compromised differentiation of odontoblasts in molars. We also found osteodentin formation in the coronal part of the cKO mandibular incisors, which was associated with a reduction in the expression of odontogenic geneDspand an increase in the expression of osteogenic geneBsp, leading to an alteration of cell fate from odontoblasts to osteoblasts. In addition, the expressions of WNT antagonists,Dkk1andSost, were downregulated andB-cateninwas up-regulated in the cKO incisors, while the expression levels were not changed in the cKO molars, compared with the corresponding controls. Our results indicate the distinct and critical roles of ACVR1 between incisors and molars, which is associated with alterations in the WNT signaling related molecules. This study demonstrates for the first time the physiological roles of ACVR1 during dentinogenesis.