Overactivation of the NF-κB pathway impairs molar enamel formation


  • A. Yamada
  • M. Kawasaki
  • Y. Miake
  • Y. Yamada
  • J. Blackburn
  • K. Kawasaki
  • S. Trakanant
  • T. Nagai
  • J. Nihara
  • T. Kudo
  • F. Meguro
  • R. Schmidt-Ullrich
  • B. Liu
  • Y. Hu
  • A. Page
  • Á. Ramírez
  • P.T. Sharpe
  • T. Maeda
  • R. Takagi
  • A. Ohazama


  • Oral Diseases


  • Oral Dis 26 (7): 1513-1522


  • 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.