Disturbance of the Nuclear Factor I-C Gene Induces Apoptosis in Odontoblast During Tooth Root Development

Abstract

Nfic (-/-) mice demonstrated aberrant odontoblast differentiation, abnormal dentin formation, and thus molar lacking roots. However, other tissues/organs in the body including ameloblasts appeared to be unaffected and normal. In the present study, first we observed the expression of p-Smad2/3 and TGFβ-RI in Nfic (-/-) mice. Second, we investigated if disruption of Nfic gene causes apoptosis of odontoblasts. Third, we examined to uncover the molecular mechanism of apoptosis in Nfic (-/-) odontoblasts. Initial studies demonstrated that disturbance of the Nfic gene increased both TGFβ-RI and p-Smad2/3 expression in aberrant odontoblasts and pulp cells in the sub-odontoblastic layer. Analysis of apoptotic cells in the sub-odontoblastic layer of the pulp in Nfic (-/-) mice exhibited an increased apoptotic activity. Further, Nfic (-/-) primary pulp cells increased not only the expression of Fas and FasL but also the activation of caspase-8 and -3, while the cleaved form of Bid was hardly detected. These findings indicate that NFI-C plays important roles in regulation of differentiation and apoptosis in odontoblasts during tooth root formation.