Nuclear factor I-C regulates intramembranous bone formation via control of FGF signalling
Jieun Lee,
Joo-Cheol Park,
Heung‐Joong Kim,
Hyun Sook Bae,
Dong-Seol Lee
Affiliations
Jieun Lee
Department of Oral Hygiene, Namseoul University, Cheonan, Republic of Korea
Joo-Cheol Park
Department of Oral Histology-Developmental Biology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, Republic of Korea; Regenerative Dental Medicine R and D Center, Hysensbio Co., Ltd., Seoul, Republic of Korea
Heung‐Joong Kim
Department of Anatomy and Orofacial Development School of Dentistry Chosun University, Dong-gu, Gwangju, Republic of Korea
Hyun Sook Bae
Department of Oral Hygiene, Namseoul University, Cheonan, Republic of Korea; Corresponding author. Department of Oral Hygiene, Namseoul University, Cheonan, 31020, Republic of Korea.
Dong-Seol Lee
Department of Oral Histology-Developmental Biology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, Republic of Korea; Regenerative Dental Medicine R and D Center, Hysensbio Co., Ltd., Seoul, Republic of Korea; Corresponding author. Department of Oral Histology-Developmental Biology, School of Dentistry and Dental Research Institute, Seoul National University, 1, Gwanak-ro, Gwanak-gu, Seoul, 08826, Republic of Korea.
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 Nfic gene leads to defects in intramembranous bone formation, characterized by decreased osteogenic proliferative activity and reduced osteoblast differentiation during postnatal osteogenesis. Additionally, Nfic-deficient mice exhibited incomplete suture closure, although Nfic 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 Nfic-deficient mice. In contrast, NFI-C overexpression in human bone marrow stromal cells (hBMSCs) significantly increased the expression of these factors. Furthermore, NFI-C regulates FGFR1 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.
