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.
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We thank Dr. T. Sugiyama (Akita University School of Medicine, Akita, Japan) for providing ameloblast-lineage cell line (ALC).
This research was supported by the National Research Foundation of Korea (NRF) grant (NRF-2015M3A9B6052852) and by Basic Science Research Program through the NRF grant funded by the Ministry of Science, ICT & Future Planning (NRF-2014R1A1A1005439).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflicts of interest.
All experiments involving mice were performed according to the Dental Research Institute guidelines and the Institutional Animal Care and Use Committees of Seoul National University (SNU-111013-2).
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