Laboratory for the Study of Regenerative Dental Medicine, Department of Oral Histology-Developmental Biology & Dental Research Institute, School of Dentistry, Seoul National University, 86 dong-506, Gwanak-ro, Gwanak-gu, Seoul, 08826, South Korea.
Cell Tissue Res. 2018 Dec;374(3):531-540. doi: 10.1007/s00441-018-2901-3. Epub 2018 Aug 9.
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.
釉质构成牙冠的最外层，其硬度可保护其他牙齿组织免受各种刺激。釉质一旦受损就无法再生，因为在牙齿萌出过程中，成釉细胞会丢失。由于成釉细胞分化机制尚不清楚，因此进一步的研究对于开发针对缺陷或受损釉质的治疗方法至关重要。先前，我们曾报道过，成骨细胞分化和骨形成是通过 runt 相关转录因子 2（Runx2）-核因子 1-C（Nfic）-骨形成蛋白 4（Osx）途径来调节的，其中 Nfic 可直接控制 Osx 的表达。该途径还调节成牙本质细胞分化和牙本质形成。本研究旨在探讨相同的途径是否适用于成釉细胞分化。在 Nfic 小鼠切牙中观察到结构型釉质缺陷，表现为成釉细胞排列紊乱，颈环增殖活性降低。Nfic 小鼠的成釉细胞分化标志物的表达也显著下调。实时 PCR 分析表明，Runx2、Nfic 和 Osx 调节成釉细胞分化标志物的表达，其中 Runx2 位于 Nfic 的上游，而 Nfic 控制 Osx 的表达。因此，我们提出 Runx2-Nfic-Osx 途径是调节成釉细胞分化的关键因素之一。
