Excessive Wnt/β-catenin signaling disturbs tooth-root formation.
OBJECTIVE
Wingless-type MMTV integration site family (Wnt)/β-catenin signaling plays an essential role in cellular differentiation and matrix formation during skeletal development. However, little is known about its role in tooth-root formation. In a previous study, we found excessive formation of dentin and cementum in mice with constitutive β-catenin stabilization in the dental mesenchyme. In the present study we analyzed the molar roots of these mice to investigate the role of Wnt/β-catenin signaling in root formation in more detail.


METHODS
We generated OC-Cre:Catnb(+/lox(ex3)) mice by intercrossing Catnb(+/lox(ex3)) and OC-Cre mice, and we analyzed their mandibular molars using radiography, histomorphometry and immunohistochemistry.


RESULTS
OC-Cre:Catnb(+/lox(ex3)) mice showed impaired root formation. At the beginning of root formation in mutant molars, dental papilla cells did not show normal differentiation into odontoblasts; rather, they were prematurely differentiated and had a disorganized arrangement. Interestingly, SMAD family member 4 was upregulated in premature odontoblasts. In 4-wk-old mutant mice, molar roots were about half the length of those in their wild-type littermates. In contrast to excessively formed dentin in crown, root dentin was thin and hypomineralized in mutant mice. Biglycan and dentin sialophosphoprotein were downregulated in root dentin of mutant mice, whereas dentin matrix protein 1 and Dickkopf-related protein 1 were upregulated. Additionally, ectonucleotide pyrophosphatase/phosphodiesterase 1 was significantly downregulated in the cementoblasts of mutant molars. Finally, in the cementum of mutant mice, bone sialoprotein was downregulated but Dickkopf-related protein 2 was upregulated.


CONCLUSIONS
These results suggest that temporospatial regulation of Wnt/β-catenin signaling plays an important role in cell differentiation and matrix formation during root and cementum formation.
Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences, Chonbuk National University School of Dentistry, Jeonju, South Korea.
C H
CH
Bae
J Y
JY
Lee
T H
TH
Kim
J A
JA
Baek
J C
JC
Lee
X
X
Yang
M M
MM
Taketo
R
R
Jiang
E S
ES
Cho
D000818:Animals; D058578:Biglycan / Q000032:analysis; D002454:Cell Differentiation / Q000502:physiology; D016764:Cell Polarity / Q000502:physiology; D025021:Cementogenesis / Q000502:physiology; D003739:Dental Cementum / Q000473:pathology; D003771:Dental Papilla / Q000473:pathology; D003804:Dentin / Q000473:pathology; D003810:Dentinogenesis / Q000502:physiology; D015536:Down-Regulation; D016326:Extracellular Matrix Proteins / Q000032:analysis; D058574:Integrin-Binding Sialoprotein / Q000032:analysis; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis; D051379:Mice; D008817:Mice, Mutant Strains; D008963:Molar / Q000254:growth & development; D009154:Mutation / Q000235:genetics; D009804:Odontoblasts / Q000473:pathology; D009805:Odontogenesis / Q000502:physiology*; D010750:Phosphoproteins / Q000032:analysis; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases; D012795:Sialoglycoproteins / Q000032:analysis; D015398:Signal Transduction / Q000502:physiology; D051901:Smad4 Protein / Q000032:analysis; D014092:Tooth Root / Q000254:growth & development*; D015854:Up-Regulation; D060449:Wnt Signaling Pathway / Q000235:genetics / Q000502:physiology*; D000099311:Dentin Sialophosphoprotein
D058578:Biglycan; D016326:Extracellular Matrix Proteins; D058574:Integrin-Binding Sialoprotein; D036341:Intercellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases; D012795:Sialoglycoproteins; D051901:Smad4 Protein; D000099311:Dentin Sialophosphoprotein; C546885:Bgn protein, mouse; C501127:Dkk1 protein, mouse; C405060:Dkk2 protein, mouse; C513308:Dmp1 protein, mouse; C546872:Ibsp protein, mouse; C490810:Smad4 protein, mouse; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1