Overactivation of the NF-κB pathway impairs molar enamel formation

Akane Yamada, Maiko Kawasaki, Yasuo Miake, Yurie Yamada, James Blackburn, Katsushige Kawasaki, Supaluk Trakanant, Takahiro Nagai, Jun Nihara, Takehisa Kudo, Fumiya Meguro, Ruth Schmidt-Ullrich, Bigang Liu, Yinling Hu, Angustias Page, Ángel Ramírez, Paul T. Sharpe, Takeyasu Maeda, Ritsuo Takagi, Atsushi Ohazama*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)


Objective: Hypohidrotic ectodermal dysplasia (HED) is a hereditary disorder characterized by abnormal structures and functions of the ectoderm-derived organs, including teeth. HED patients exhibit a variety of dental symptoms, such as hypodontia. Although disruption of the EDA/EDAR/EDARADD/NF-κB pathway is known to be responsible for HED, it remains unclear whether this pathway is involved in the process of enamel formation. Experimental subjects and methods: To address this question, we examined the mice overexpressing Ikkβ (an essential component required for the activation of NF-κB pathway) under the keratin 5 promoter (K5-Ikkβ). Results: Upregulation of the NF-κB pathway was confirmed in the ameloblasts of K5-Ikkβ mice. Premature abrasion was observed in the molars of K5-Ikkβ mice, which was accompanied by less mineralized enamel. However, no significant changes were observed in the enamel thickness and the pattern of enamel rods in K5-Ikkβ mice. Klk4 expression was significantly upregulated in the ameloblasts of K5-Ikkβ mice at the maturation stage, and the expression of its substrate, amelogenin, was remarkably reduced. This suggests that abnormal enamel observed in K5-Ikkβ mice was likely due to the compromised degradation of enamel protein at the maturation stage. Conclusion: Therefore, we could conclude that the overactivation of the NF-κB pathway impairs the process of amelogenesis.

Original languageEnglish
Pages (from-to)1513-1522
Number of pages10
JournalOral Diseases
Issue number7
Publication statusPublished - 1 Oct 2020


  • NF-κB
  • enamel
  • molar
  • tooth development


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