Nuclear factor I-C regulates intramembranous bone formation via control of FGF signalling

Our previous studies indicate that NFI-C is essential for tooth root development and endochondral ossification. However, its exact role in calvarial intramembranous bone formation remains unclear. In this study, we demonstrate that the disruption of the <i>Nfic</i> gene leads to defects in intramembranous bone formation, characterized by decreased osteogenic proliferative activity and reduced osteoblast differentiation during postnatal osteogenesis. Additionally, <i>Nfic</i>-deficient mice exhibited incomplete suture closure, although <i>Nfic</i> disruption did not affect prenatal calvarial bone development. We found that the expression levels of Fgfr1 and Fgfr2 were reduced in the primary calvarial mesenchymal cells of <i>Nfic</i>-deficient mice. In contrast, NFI-C overexpression in human bone marrow stromal cells (hBMSCs) significantly increased the expression of these factors. Furthermore, <i>NFI-C</i> regulates <i>FGFR1</i> expression by directly binding to its promoter. These results indicate that NFI-C is crucial in regulating calvarial bone formation and suture closure by controlling Fgfr1 expression and cellular proliferation.