Nuclear factor I-C expression pattern in developing teeth and its important role in odontogenic differentiation of human molar stem cells from the apical papilla.

Abstract

Nuclear factor I-C (NFIC) has an important role in the development of murine dental roots, but its role in human root formation is unreported. We thus elucidated the regulatory role of NFIC in the differentiation of human stem cells from the apical papilla (hSCAPs). The first step for this was to determine the expression of NFIC in human teeth, and it was found that NFIC expression was restricted to the odontoblasts and preodontoblasts of the developing molars of humans and mice. NFIC was found to be expressed in odontoblast-like cells after the subcutaneous transplantation of hSCAPs. NFIC expression was concomitant with dentin sialophosphoprotein (DSPP) in the mineralization of hSCAPs. NFIC knockdown in hSCAPs significantly inhibited expression of DSPP and promoted that of dentin matrix protein 1 (DMP1), meanwhile upregulated the expression of TGF-β1 and downregulated SMAD3 and SMAD4. NFIC expression was significantly upregulated after TGF-β1 treatment in hSCAPs. NFIC knockdown prolonged G1 phase of the cell cycle, but had no effect on cell proliferation and migration. These results suggest that NFIC is involved in the development of human root dentin and the regulation of odontoblastic differentiation of hSCAPs. NFIC may participate in the DMP1-DSPP signaling pathway and comprises a complex signaling cycle with TGF-β1.