title: Nuclear factor I-C (NFIC) regulates dentin sialophosphoprotein (DSPP) and E-cadherin via control of Krüppel-like factor 4 (KLF4) during dentinogenesis.
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.
authors.affiliation: From the Department of Oral Histology-Developmental Biology and Dental Research Institute, School of Dentistry, Seoul National University, 101 Daehagro, Chongro-gu, Seoul 110-749, Korea and.
authors.forename: Hye-Kyung
authors.initials: HK
authors.lastname: Lee
authors.affiliation: From the Department of Oral Histology-Developmental Biology and Dental Research Institute, School of Dentistry, Seoul National University, 101 Daehagro, Chongro-gu, Seoul 110-749, Korea and.
authors.forename: Dong-Seol
authors.initials: DS
authors.lastname: Lee
authors.affiliation: From the Department of Oral Histology-Developmental Biology and Dental Research Institute, School of Dentistry, Seoul National University, 101 Daehagro, Chongro-gu, Seoul 110-749, Korea and.
authors.forename: Su-Jin
authors.initials: SJ
authors.lastname: Park
authors.affiliation: the Department of Dental Hygiene, Namseoul University, Cheon-An, Chung-Nam 331-707, Korea.
authors.forename: Kwang-Hee
authors.initials: KH
authors.lastname: Cho
authors.affiliation: the Department of Dental Hygiene, Namseoul University, Cheon-An, Chung-Nam 331-707, Korea.
authors.forename: Hyun-Sook
authors.initials: HS
authors.lastname: Bae
authors.affiliation: From the Department of Oral Histology-Developmental Biology and Dental Research Institute, School of Dentistry, Seoul National University, 101 Daehagro, Chongro-gu, Seoul 110-749, Korea and jcapark@snu.ac.kr.
authors.forename: Joo-Cheol
authors.initials: JC
authors.lastname: Park
mesh_terms: D000565:Ameloblasts / Q000166:cytology / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation; D003804:Dentin / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D003810:Dentinogenesis / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D057809:HEK293 Cells; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics* / Q000378:metabolism; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D051839:NFI Transcription Factors / Q000235:genetics* / Q000378:metabolism; D009804:Odontoblasts / Q000166:cytology / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D051381:Rats; D012795:Sialoglycoproteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic; D000099311:Dentin Sialophosphoprotein
chemical_list: D015820:Cadherins; D016326:Extracellular Matrix Proteins; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D008156:Luciferases; D051839:NFI Transcription Factors; D010750:Phosphoproteins; D012795:Sialoglycoproteins; D000099311:Dentin Sialophosphoprotein; C081635:Dmp1 protein, rat; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; C000715469:Klf4 protein, rat; C497649:Nfic protein, rat
keywords: DSPP; Dentin; Dentinogenesis; Differentiation; Gene Regulation; KLF5; NFIC; Odontoblast; Signaling; Tooth Development