ALK5 is essential for tooth germ differentiation during tooth development
ALK5 is essential for tooth germ differentiation during tooth development
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ALK5 对于牙齿发育过程中的牙胚分化至关重要。
DOI：
10.1080/10520295.2018.1552018
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发表时间：
2019-05-26
影响因子：
1.6
通讯作者：
Du, J.
中科院分区：
文献类型：
--
作者：
Guo, W.;Fan, Z.;Du, J.
蛋白质 TGF β 超家族参与牙齿发育。 TGF beta 1 和 TGF beta 3 调节成牙本质细胞分化和牙本质细胞外基质合成。尽管 TGF β 家族成员配体在哺乳动物牙齿发育过程中的表达已得到充分表征，但人们对 TGF β 受体知之甚少，TGF β 受体是由 I 型和 II 型受体组成的异聚复合物。 ALK5 (TGF beta R1) 在牙齿间充质中的分子机制尚不清楚。我们研究了 ALK5 在 15.5 天胚胎小鼠下第一磨牙牙胚的牙胚间充质细胞 (TGMC) 中的作用。将人重组 TGF beta 3 蛋白或 ALK5 抑制剂 (SD208) 添加到细胞中。 SD208 抑制细胞增殖，TGF beta 3 促进细胞增殖。我们发现 SD208 抑制 TGMC 成骨和牙本质形成。经典和非经典 TGF β 信号通路都参与了该过程。当 ALK5 受到抑制时，TAK1、P-TAK1、p38 和 P-p38 显示出较高的表达，而 SMAD4 显示出较少的表达。我们的研究结果有助于理解 TGF β 信号传导在牙胚来源的间充质干细胞分化中的作用，并提出了优化牙源干细胞用于组织再生的可能目标。
The TGF beta superfamily of proteins participates in tooth development. TGF beta 1 and TGF beta 3 regulate odontoblast differentiation and dentin extracellular matrix synthesis. Although the expression of TGF beta family member ligands is well-characterized during mammalian tooth development, less is known about the TGF beta receptor, which is a heteromeric complex consisting of a type I and type II receptors. The molecular mechanism of ALK5 (TGF beta R1) in the dental mesenchyme is not clear. We investigated the role of ALK5 in tooth germ mesenchymal cells (TGMCs) from the lower first molar tooth germs of day 15.5 embryonic mice. Human recombinant TGF beta 3 protein or an ALK5 inhibitor (SD208) was added to the cells. Cell proliferation was inhibited by SD208 and promoted by TGF beta 3. We found that SD208 inhibited TGMCs osteogenesis and dentinogenesis. Both canonical and noncanonical TGF beta signaling pathways participated in the process. TAK1, P-TAK1, p38 and P-p38 showed greater expression and SMAD4 showed less expression when ALK5 was inhibited. Our findings contribute to understanding the role of TGF beta signaling for the differentiation of mesenchymal stem cells derived from dental germ and suggest possible targets for optimizing the use of stem cells of dental origin for tissue regeneration.