Cell and Tissue Research

, Volume 374, Issue 3, pp 531–540 | Cite as

The Nfic-osterix pathway regulates ameloblast differentiation and enamel formation

  • D. S. Lee
  • Song Yi Roh
  • Joo-Cheol ParkEmail author
Regular Article


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.


Runt-related transcription factor 2 Nuclear factor 1-C Osterix Ameloblast Enamel 



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.

Ethical approval

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).

Supplementary material

441_2018_2901_MOESM1_ESM.docx (15 kb)
ESM 1 (DOCX 14 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Laboratory for the Study of Regenerative Dental Medicine, Department of Oral Histology-Developmental Biology & Dental Research Institute, School of DentistrySeoul National UniversitySeoulSouth Korea

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