S-Space College of Dentistry/School of Dentistry (치과대학/치의학대학원) Dept. of Dentistry (치의학과) Journal Papers (저널논문_치의학과)
Zinc is Essential for NFI-C Signaling for the Regulation of Odontoblast Differentiation.
- Oh, Hyun-Jung; Lee, Hye-Kyung; Park, Su-Jin; Cho, Young-Sik; Bae, Hyun-Sook; Cho, Moon-Il; Park, Joo-Cheol
- Issue Date
- JOURNAL OF CELLULAR BIOCHEMISTRY Vol.113 No.113, pp. 877-887
- Zinc is trace element essential for diverse metabolic and cellular signaling pathways for the growth, development, and maintenance. Zinc
deficiency is involved in bone malformations and oral disease. Mice deficient in zinc transporter Zip13 show connective tissue and skeletal
disorders, abnormal incisor teeth, and reduced root dentin formation in the molar teeth and share a morphologically similar phenotype to
nuclear factor I-C (NFI-C)-deficient mice. However, the precise function of zinc in NFI-C signaling-mediated odontoblast differentiation and
dentin formation remains unclear. Here, we show that zinc stimulated the expression of metal transcription factor-1, but decreased NFI-C
expression in odontoblastic MDPC-23 cells. Zinc also enhanced the phosphorylation of Smad2/3 (p-Smad2/3) and increased the binding
efficiency of NFI-C and p-Smad2/3 in the cytoplasm. In contrast, zinc deficiency resulted in the accumulation of NFI-C into nucleus.
Consequently, NFI-C had the biologic properties of a transcription factor, including DNA binding affinity for metallothionein-1 and the dentin
sialophosphoprotein (DSPP) promoter, and transcriptional activation of the DSPP gene. Furthermore, zinc deficiency condition promoted
DSPP expression in odontoblasts and dentin mineralization, while zinc sufficiency condition decreased DSPP expression and slightly delayed
dentin mineralization. These data suggest that zinc equilibrium is required for odontoblast differentiation and dentin formation during
dentinogenesis through the nuclear accumulation and modulation of NFI-C.
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