Antagonistic Functions of USAG-1 and RUNX2 during Tooth Development.
Antagonistic Functions of USAG-1 and RUNX2 during Tooth Development.
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USAG-1 和 RUNX2 在牙齿发育过程中的拮抗功能。
DOI：
10.1371/journal.pone.0161067
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Bessho K
中科院分区：
文献类型：
--
作者：
Togo Y;Takahashi K;Saito K;Kiso H;Tsukamoto H;Huang B;Yanagita M;Sugai M;Harada H;Komori T;Shimizu A;MacDougall M;Bessho K
多生牙和牙齿发育不全是人类常见的形态异常。我们以前获得的证据表明，多余的上颌切牙的形式作为一个结果的连续发展的残迹上颌切牙牙胚在Usag-1无效小鼠。在Runx 2基因敲除小鼠中，牙胚的发育被阻止，并且这些小鼠还表现出与上磨牙和切牙相关的舌上皮芽。本研究的目的是调查在牙齿发育过程中Usag-1和Runx 2之间的潜在串扰。在本研究中，观察到三个有趣的现象，在双无效Usag-1-/-/Runx 2-/-小鼠：多生牙的患病率低于Usag-1 null小鼠;牙齿发育进一步进行相比，在Runx 2 null小鼠;和磨牙舌芽的频率低于Runx 2 null小鼠。因此，我们认为RUNX 2和USAG-1以拮抗的方式起作用。在Usag-1+/+/Runx 2-/-小鼠中，舌芽完全充满牙源性上皮Sox 2阳性细胞，而在Usag-1-/-/Runx 2 +/+小鼠的残基上颌切牙中，几乎没有牙源性上皮Sox 2阳性细胞有助于多生牙的形成。我们的研究结果表明，RUNX 2直接或间接地阻止牙源性上皮Sox 2阳性细胞的分化和/或增殖。我们假设RUNX 2抑制骨形态发生蛋白（BMP）和/或由USAG-1调节的Wnt信号通路，而RUNX 2表达由独立于USAG-1的BMP信号转导诱导。
Supernumerary teeth and tooth agenesis are common morphological anomalies in humans. We previously obtained evidence that supernumerary maxillary incisors form as a result of the successive development of the rudimentary maxillary incisor tooth germ in Usag-1 null mice. The development of tooth germs is arrested in Runx2 null mice, and such mice also exhibit lingual epithelial buds associated with the upper molars and incisors. The aim of this study is to investigate the potential crosstalk between Usag-1 and Runx2 during tooth development. In the present study, three interesting phenomena were observed in double null Usag-1-/-/Runx2-/- mice: the prevalence of supernumerary teeth was lower than in Usag-1 null mice; tooth development progressed further compared than in Runx2 null mice; and the frequency of molar lingual buds was lower than in Runx2 null mice. Therefore, we suggest that RUNX2 and USAG-1 act in an antagonistic manner. The lingual bud was completely filled with odontogenic epithelial Sox2-positive cells in the Usag-1+/+/Runx2-/- mice, whereas almost no odontogenic epithelial Sox2-positive cells contributed to supernumerary tooth formation in the rudimentary maxillary incisors of the Usag-1-/-/Runx2+/+ mice. Our findings suggest that RUNX2 directly or indirectly prevents the differentiation and/or proliferation of odontogenic epithelial Sox2-positive cells. We hypothesize that RUNX2 inhibits the bone morphogenetic protein (BMP) and/or Wnt signaling pathways regulated by USAG-1, whereas RUNX2 expression is induced by BMP signaling independently of USAG-1.