Abstract
Odontoblasts are a type of terminally differentiated matrix-secreting cells. A number of molecular mechanisms are involved in the differentiation of odontoblasts. Several studies demonstrated that Krüppel-like factor 4 (KLF4) promotes odontoblast differentiation via control of dentin sialophosphoprotein (DSPP). Because nuclear factor I-C (NFIC) is also known to control DSPP, we investigated the relationship between NFIC and KLF4 during odontoblast differentiation. Klf4 mRNA expression was significantly decreased in Nfic(-/-) pulp cells compared with wild type cells. In immunohistochemistry assays, dentin matrix protein 1 (Dmp1), and DSP protein expression was barely observed in Nfic(-/-) odontoblasts and dentin matrix. Nfic bound directly to the Klf4 promoter and stimulated Klf4 transcriptional activity, thereby regulating Dmp1 and DSPP expression during odontoblast differentiation. Nfic or Klf4 overexpression promoted mineralized nodule formation in MDPC-23 cells. In addition, Nfic overexpression also decreased Slug luciferase activity but augmented E-cadherin promoter activity via up-regulation of Klf4 in odontoblasts. Our study reveals important signaling pathways during dentinogenesis: the Nfic-Klf4-Dmp1-Dspp and the Nfic-Klf4-E-cadherin pathways in odontoblasts. Our results indicate the important role of NFIC in regulating KLF4 during dentinogenesis.
Highlights
The role of nuclear factor I-C (NFIC) and Krüppel-like factor 4 (KLF4) and their interrelationship during dentinogenesis remain unclear
Because nuclear factor I-C (NFIC) is known to control dentin sialophosphoprotein (DSPP), we investigated the relationship between NFIC and KLF4 during odontoblast differentiation
Among 190,230 probes on the BeadChip, 2,338 genes differed by factors of greater than 2-fold in pulp cells of NficϪ/Ϫ mice compared with wild type
Summary
The role of NFIC and KLF4 and their interrelationship during dentinogenesis remain unclear. Results: Our study establishes the Nfic-Klf dentin matrix protein 1 (Dmp1)-Dspp pathway in odontoblasts. Several studies demonstrated that Krüppel-like factor 4 (KLF4) promotes odontoblast differentiation via control of dentin sialophosphoprotein (DSPP). Because nuclear factor I-C (NFIC) is known to control DSPP, we investigated the relationship between NFIC and KLF4 during odontoblast differentiation. Nfic bound directly to the Klf promoter and stimulated Klf transcriptional activity, thereby regulating Dmp and DSPP expression during odontoblast differentiation. KLF4 overexpression in human dental pulp cells led to down-regulate the cell proliferation rate and up-regulate odontoblast-related genes, such as dentin matrix protein 1 (DMP1), DSPP, and alkaline phosphatase (ALP) [11, 12]. We investigated the roles of NFIC and KLF4 and their relationship during odontoblast differentiation and dentin formation
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