Microtubule-associated protein tau (Mapt) is expressed in terminally differentiated odontoblasts and severely down-regulated in morphologically disturbed odontoblasts of Runx2 transgenic mice
Microtubule-associated protein tau (Mapt) is expressed in terminally differentiated odontoblasts and severely down-regulated in morphologically disturbed odontoblasts of Runx2 transgenic mice
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DOI：
10.1007/s00441-015-2135-6
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发表时间：
2015-08-01
影响因子：
3.6
通讯作者：
Komori, Toshihisa
中科院分区：
文献类型：
--
作者：
Miyazaki, Toshihiro;Baba, Tomomi T.;Komori, Toshihisa
Runx 2是成骨细胞、成牙本质细胞分化和软骨细胞终末分化的重要转录因子。我们以前已经表明，在Runx 2转基因{Tg（Col 1a 1-Runx 2）}小鼠中，在2.3 kb Col 1a 1启动子的控制下，成牙本质细胞的终末分化受到抑制，该启动子指导转基因表达成骨细胞和成牙本质细胞。在Tg（Col 1a 1-Runx 2）小鼠中，成牙本质细胞显示Dspp和巢蛋白表达严重减少，并失去其特征性极化形态，包括延伸至牙本质的长过程。我们通过比较野生型和Tg（Col 1a 1-Runx 2）小鼠磨牙中的基因表达来研究成牙本质细胞形态发生的分子机制，重点是细胞因子相关基因。使用微阵列，我们发现，微管相关蛋白tau（Mapt）的基因表达，神经元磷蛋白与神经元生物学和微管动力学和组装的重要作用，是高的野生型磨牙，但严重降低Tg（Col 1a 1-Runx 2）磨牙。免疫组化分析显示，Mapt特异性表达于终末分化的成牙本质细胞，包括野生型磨牙的突起，但其表达在Tg（Col 1a 1-Runx 2）磨牙中几乎检测不到。Mapt和Runx 2双染显示成牙本质细胞中的表达是相互的。野生型磨牙成牙本质细胞中Mapt和微管蛋白共定位。免疫电镜分析表明Mapt位于成牙本质细胞突起中α-微管蛋白阳性的丝状结构周围。因此，Mapt是终末分化成牙本质细胞的一个有用的标志物，并可能在成牙本质细胞的形态发生中发挥重要作用。
Runx2 is an essential transcription factor for osteoblast and odontoblast differentiation and the terminal differentiation of chondrocytes. We have previously shown that the terminal differentiation of odontoblasts is inhibited in Runx2 transgenic {Tg(Col1a1-Runx2)} mice under the control of the 2.3-kb Col1a1 promoter, which directs the transgene expression to osteoblasts and odontoblasts. Odontoblasts show severe reductions in Dspp and nestin expression and lose their characteristic polarized morphology, including a long process extending to dentin, in Tg(Col1a1-Runx2) mice. We study the molecular mechanism of odontoblast morphogenesis by comparing gene expression in the molars of wild-type and Tg(Col1a1-Runx2) mice, focusing on cytoskeleton-related genes. Using microarray, we found that the gene expression of microtubule-associated protein tau (Mapt), a neuronal phosphoprotein with important roles in neuronal biology and microtubule dynamics and assembly, was high in wild-type molars but severely reduced in Tg(Col1a1-Runx2) molars. Immunohistochemical analysis revealed that Mapt was specifically expressed in terminally differentiated odontoblasts including their processes in wild-type molars but its expression was barely detectable in Tg(Col1a1-Runx2) molars. Doublestaining of Mapt and Runx2 showed their reciprocal expression in odontoblasts. Mapt and tubulin co-localized in odontoblasts in wild-type molars. Immunoelectron microscopic analysis demonstrated Mapt lying around alpha-tubulin-positive filamentous structures in odontoblast processes. Thus, Mapt is a useful marker for terminally differentiated odontoblasts and might play an important role in odontoblast morphogenesis.