The Nfic-osterix pathway regulates ameloblast differentiation and enamel formation
The Nfic-osterix pathway regulates ameloblast differentiation and enamel formation
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DOI：
10.1007/s00441-018-2901-3
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发表时间：
2018-12-01
影响因子：
3.6
通讯作者：
Park, Joo-Cheol
中科院分区：
文献类型：
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作者：
Lee, D. S.;Roh, Song Yi;Park, Joo-Cheol
牙釉质是牙冠最外层的一层，它的硬度可以保护其他牙齿组织免受各种刺激。牙釉质一旦受损就不能再生，因为成釉细胞在牙萌出过程中会丢失。由于成釉细胞的分化机制尚不清楚，进一步的研究对于开发治疗有缺陷或受损的釉质是必要的。以前，我们已经报道了成骨细胞分化和骨形成是通过矮小相关转录因子2(Runx2)-核因子1-C(NFc)-OSX(OSX)途径来调节的，其中NFIC直接控制OSX的表达。该途径还调节成牙本质细胞分化和牙本质形成。这项研究的目的是探讨相同的途径是否适用于成釉细胞分化。在NFIC(-/-)小鼠的门牙中观察到结构性的釉质缺陷和紊乱的成釉细胞以及颈环的增殖活性降低。成釉细胞分化标记物在NFIC(-/-)小鼠中的表达也显著下调。实时定量聚合酶链式反应分析表明，Runx2、NFIC和OSX调控成釉细胞分化标志物的表达，其中Runx2位于NFIC的上游，NFIC控制OSX的表达。因此，我们认为Runx2-NFIC-OSX通路是调控成釉细胞分化的关键因素之一。
Enamel makes up the outermost layer of the crown and its hardness protects other dental tissues from various stimuli. Enamel cannot be regenerated once damaged because ameloblasts are lost during the tooth eruption. Since the ameloblast differentiation mechanism is still unknown, further research is essential for developing treatments for defective or damaged enamel. Previously, we have reported that osteoblast differentiation and bone formation were regulated through the runt-related transcription factor 2 (Runx2)-nuclear factor 1-C (Nfic)-osterix (Osx) pathway where Nfic directly controls Osx expression. This pathway regulates odontoblast differentiation and dentin formation as well. The aim of this study was to investigate if the same pathway is applicable for ameloblast differentiation. Structural enamel defects with disorganized ameloblasts and decreased proliferation activity of the cervical loop were observed in Nfic(-/-) mice incisors. Expression of the ameloblast differentiation markers was also downregulated significantly in Nfic(-/-) mice. Real-time PCR analyses suggested that Runx2, Nfic, and Osx regulate the expression of ameloblast differentiation markers, where Runx2 is upstream of Nfic, and Nfic controls Osx expression. Therefore, we suggest the Runx2-Nfic-Osx pathway as one of the key factors that regulate ameloblast differentiation.