ABSTRACT
Stringent regulation of the chondrocyte cell cycle is required for endochondral bone formation. During the longitudinal growth of long bones, mesenchymal stem cells condense and differentiate into chondrocytes. Epiphyseal chondrocytes sequentially differentiate to form growth- plate cartilage, which is subsequently replaced with bone. Although the importance of nuclear factor 1C (Nfic) in hard tissue formation has been extensively studied, knowledge regarding its biological roles and molecular mechanisms in this process remains insufficient. Herein, we demonstrated that Nfic deficiency affects femoral growth-plate formation. Chondrocyte proliferation was downregulated and the number of apoptotic cell was increased in the growth plates of Nfic-/- mice. Further, the expression of the cell cycle inhibitor p21 was upregulated in the primary chondrocytes of Nfic-/- mice, whereas that of cyclin D1 was downregulated. Our findings suggest that Nfic may contribute to postnatal chondrocyte proliferation by inhibiting p21 expression and by increasing the stability of cyclin D1 protein.
Subject(s)
Chondrocytes/cytology , Chondrocytes/metabolism , Growth Plate/cytology , Growth Plate/metabolism , NFI Transcription Factors/metabolism , Animals , Cell Differentiation/physiology , Cell Proliferation/physiology , Humans , MiceABSTRACT
Enamel makes up the outermost layer of the crown and its hardness protects other dental tissues from various stimuli. Enamel cannot be regenerated once damaged because ameloblasts are lost during the tooth eruption. Since the ameloblast differentiation mechanism is still unknown, further research is essential for developing treatments for defective or damaged enamel. Previously, we have reported that osteoblast differentiation and bone formation were regulated through the runt-related transcription factor 2 (Runx2)-nuclear factor 1-C (Nfic)-osterix (Osx) pathway where Nfic directly controls Osx expression. This pathway regulates odontoblast differentiation and dentin formation as well. The aim of this study was to investigate if the same pathway is applicable for ameloblast differentiation. Structural enamel defects with disorganized ameloblasts and decreased proliferation activity of the cervical loop were observed in Nfic-/- mice incisors. Expression of the ameloblast differentiation markers was also downregulated significantly in Nfic-/- mice. Real-time PCR analyses suggested that Runx2, Nfic, and Osx regulate the expression of ameloblast differentiation markers, where Runx2 is upstream of Nfic, and Nfic controls Osx expression. Therefore, we suggest the Runx2-Nfic-Osx pathway as one of the key factors that regulate ameloblast differentiation.
Subject(s)
Ameloblasts/cytology , Ameloblasts/metabolism , Cell Differentiation , Dental Enamel/metabolism , NFI Transcription Factors/metabolism , Signal Transduction , Sp7 Transcription Factor/metabolism , Animals , Biomarkers/metabolism , Cell Line , Cell Lineage , Cell Proliferation , Core Binding Factor Alpha 1 Subunit/metabolism , Dental Enamel/ultrastructure , Mice , NFI Transcription Factors/deficiency , Tooth/metabolism , Tooth/ultrastructure , X-Ray MicrotomographyABSTRACT
Nuclear factor I-C (NFI-C) plays a pivotal role in various cellular processes such as odontoblast and osteoblast differentiation. Nfic-deficient mice showed abnormal tooth and bone formation. The transplantation of Nfic-expressing mouse bone marrow stromal cells rescued the impaired bone formation in Nfic-/- mice. Studies suggest that NFI-C regulate osteogenesis and dentinogenesis in concert with several factors including transforming growth factor-ß1, Krüppel-like factor 4, and ß-catenin. This review will focus on the function of NFI-C during tooth and bone formation and on the relevant pathways that involve NFI-C.