title: Lymphoid enhancer-binding factor 1 expression precedes dentin sialophosphoprotein expression during rat odontoblast differentiation and regeneration.
abstract: BACKGROUND
  The molecular mechanisms behind odontoblast differentiation remain obscure. Lymphoid enhancer-binding factor 1 (Lef1) is a transcription factor that mediates Wnt signaling and has been suggested to regulate dentin sialophosphoprotein (Dspp) expression in vitro. This study aimed to clarify their precise relationship in the process of odontoblast differentiation in vivo.
  
  
  METHODS
  The detailed spatiotemporal expression patterns of Lef1 and Dspp together with other known and putative odontoblast differentiation markers such as P21 and heat-shock protein 25 (Hsp25) were examined by in situ hybridization and immunohistochemistry on paraffin sections of rat incisors and developing molars at postnatal days 1-100. To observe odontoblast regeneration following tooth injury, a cavity was prepared on the upper first molar of 10-week-old rats and the expressions of Lef1 and Dspp were investigated.
  
  
  RESULTS
  Following undifferentiated state expressing none of these examined markers, preodontoblasts begun to express P21, Lef1 and Hsp25 according to their progress of differentiation, although Dspp was undetectable. Immature odontoblasts commenced transcribing Dspp simultaneously with dentin calcification. Lef1, Dspp and Hsp25 were co-expressed in mature odontoblasts. In contrast to continuously growing incisors, Lef1, Dspp and P21 were down-regulated in the resting odontoblasts in molars when primary dentin formation was completed. Remarkably, Lef1 expression also preceded Dspp expression in newly differentiated odontoblast-like cells during the pulpal healing process after tooth injury.
  
  
  CONCLUSIONS
  Lef1 expression precedes Dspp expression without exception in both primary and reparative dentinogeneses. Our results suggest that Lef1 might play a key role in odontoblast differentiation through regulating Dspp expression.
authors.affiliation: Division of Anatomy and Cell Biology of Hard Tissue, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, Chuo-ku, Niigata, Japan.
authors.forename: Mitsushiro
authors.initials: M
authors.lastname: Nakatomi
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ida-Yonemochi
authors.forename: Hayato
authors.initials: H
authors.lastname: Ohshima
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D003804:Dentin / Q000254:growth & development; D003810:Dentinogenesis / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics; D007180:Incisor / Q000254:growth & development; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000235:genetics*; D008963:Molar / Q000166:cytology / Q000254:growth & development / Q000293:injuries; D009804:Odontoblasts / Q000502:physiology*; D010750:Phosphoproteins / Q000235:genetics*; D047428:Protein Kinase Inhibitors / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration / Q000235:genetics; D012795:Sialoglycoproteins / Q000235:genetics*; D014074:Tooth Calcification / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics; D060449:Wnt Signaling Pathway / Q000235:genetics; D000099311:Dentin Sialophosphoprotein
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D016326:Extracellular Matrix Proteins; D055551:HSP27 Heat-Shock Proteins; D051821:Lymphoid Enhancer-Binding Factor 1; D010750:Phosphoproteins; D047428:Protein Kinase Inhibitors; D012795:Sialoglycoproteins; D000099311:Dentin Sialophosphoprotein; C486114:Hspb1 protein, rat; C497575:Lef1 protein, rat