Overactivation of the NF-κB pathway impairs molar enamel formation

Abstract

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-kappa B 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 overexpressingIkk beta(an essential component required for the activation of NF-kappa B pathway) under the keratin 5 promoter (K5-Ikk beta). Results: Upregulation of the NF-kappa B pathway was confirmed in the ameloblasts ofK5-Ikk beta mice. Premature abrasion was observed in the molars ofK5-Ikk beta mice, which was accompanied by less mineralized enamel. However, no significant changes were observed in the enamel thickness and the pattern of enamel rods inK5-Ikk beta mice.Klk4expression was significantly upregulated in the ameloblasts ofK5-Ikk beta mice at the maturation stage, and the expression of its substrate, amelogenin, was remarkably reduced. This suggests that abnormal enamel observed inK5-Ikk beta 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-kappa B pathway impairs the process of amelogenesis.