Nuclear Factor I-C Is Essential for Odontogenic Cell Proliferation and Odontoblast Differentiation during Tooth Root Development

Abstract

Our previous studies have demonstrated that nuclear factor I-C (NFI-C) null mice developed short molar roots that contain aberrant odontoblasts and abnormal dentin formation. Based on these findings, we performed studies to elucidate the function of NFI-C in odontoblasts. Initial studies demonstrated that aberrant odontoblasts become dissociated and trapped in an osteodentin-like mineralized tissue. Abnormal odontoblasts exhibit strong BSP expression, but a decreased level of DSPP expression when compared to wild type odontoblasts. Loss of Nfic result in an increase in p-Smad2/3 expression in aberrant odontoblasts and pulp cells in the sub-odontoblastic layer in vivo, and primary pulp cells from Nfic-deficient mice in vitro. Cell proliferation analysis of both cervical loop and ectomesenchymal cells of the Nfic-deficient mice revealed significantly decreased proliferative activity compared to wild type mice. In addition, Nfic-deficient primary pulp cells showed increased expression of p21 and p16, but decreased expression of cyclin D1 and cyclin B1, strongly suggesting cell growth arrest due to lack of Nfic activity. Analysis of the pulp and abnormal dentin in Nfic-deficient mice revealed an increase in apoptotic activity. Further, Nfic-deficient primary pulp cells exhibited an increase in caspase-8 and -3 activation, while the cleaved form of Bid was hardly detected. These results indicate that the loss of Nfic leads to the suppression of odontogenic cell proliferation, differentiation, and induces apoptosis of aberrant odontoblasts during root formation, thereby contributing to the formation of short roots