Zinc balance is critical for NFI-C mediated regulation of odontoblast differentiation.
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.
Department of Oral Histology-Developmental Biology, School of Dentistry and Dental Research Institute, BK 21, Seoul National University, Seoul 110-749, Korea.
Hyun-Jung
HJ
Oh
Hye-Kyung
HK
Lee
Su-Jin
SJ
Park
Young-Sik
YS
Cho
Hyun-Sook
HS
Bae
Moon-Il
MI
Cho
Joo-Cheol
JC
Park
D000818:Animals; D002113:Calcification, Physiologic / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D003804:Dentin / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008668:Metallothionein / Q000235:genetics; D051379:Mice; D051839:NFI Transcription Factors / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D009804:Odontoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics; D011401:Promoter Regions, Genetic; D012795:Sialoglycoproteins / Q000235:genetics; D015533:Transcriptional Activation; D015032:Zinc / Q000494:pharmacology*; D000099311:Dentin Sialophosphoprotein
D016326:Extracellular Matrix Proteins; D008668:Metallothionein; D051839:NFI Transcription Factors; D010750:Phosphoproteins; D012795:Sialoglycoproteins; D015032:Zinc; D000099311:Dentin Sialophosphoprotein