Smad4-dependent transforming growth factor-β family signaling regulates the differentiation of dental epithelial cells in adult mouse incisors.
Smad4-dependent transforming growth factor-β family signaling regulates the differentiation of dental epithelial cells in adult mouse incisors.
复制标题
Smad4 依赖性转化生长因子-β 家族信号传导调节成年小鼠门牙牙上皮细胞的分化。
DOI：
10.1016/j.bone.2020.115456
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发表时间：
2020
期刊：
影响因子：
4.1
通讯作者：
Katagiri T.
中科院分区：
文献类型：
--
作者：
Machiya A;Tsukamoto S;Ohte S;Kuratani M;Suda N;Katagiri T.
牙齿由两种主要组织组成，牙釉质和牙本质，它们分别由上皮细胞和间充质细胞在发育过程中形成。啮齿动物的门牙是研究牙齿形成的分子机制的有用的实验模型，因为它们不仅在胚胎中而且在成体中同时生长。转化生长因子-β（TGF-β）家族成员通过必需的辅激活因子Smad 4调节上皮-间充质相互作用。在本研究中，我们建立了Smad 4条件性基因敲除（cKO）小鼠，并检查了成年切牙的表型。Smad 4 cKO小鼠在一个月内死于严重贫血。在对照和Smad 4 cKO小鼠的上皮细胞中检测到磷酸化Smad 1/5/9和Smad 2/3。在Smad 4 cKO小鼠中观察到紊乱和发育不良的上皮细胞，如成釉细胞。此外，碱性磷酸酶的表达和铁的积累减少牙上皮细胞在Smad 4 cKO小鼠。这些结果表明，TGF-β家族通过Smad 4信号传导是成年小鼠切牙中牙上皮细胞分化和功能所必需的。
Teeth consist of two major tissues, enamel and dentin, which are formed during development by epithelial and mesenchymal cells, respectively. Rodent incisors are useful experimental models for studying the molecular mechanisms of tooth formation because they are simultaneously growing in not only embryos but also adults. Members of the transforming growth factor-β (TGF-β) family regulate epithelial-mesenchymal interactions through an essential coactivator, Smad4. In the present study, we established Smad4 conditional knockout (cKO) mice and examined phenotypes in adult incisors. Smad4 cKO mice died with severe anemia within one month. Phosphorylated Smad1/5/9 and Smad2/3 were detected in epithelial cells in both control and Smad4 cKO mice. Disorganized and hypoplastic epithelial cells, such as ameloblasts, were observed in Smad4 cKO mice. Moreover, alkaline phosphatase expression and iron accumulation were reduced in dental epithelial cells in Smad4 cKO mice. These findings suggest that TGF-β family signaling through Smad4 is required for the differentiation and functions of dental epithelial cells in adult mouse incisors.