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Col1a1-cre mediated activation of β-catenin leads to aberrant dento-alveolar complex formation.

Kim TH, Bae CH, Jang EH, Yoon CY, Bae Y, Ko SO, Taketo MM, Cho ES - Anat Cell Biol (2012)

Bottom Line: Lower incisors and molars did not erupt.These results indicate that local activation of β-catenin in the osteoblasts and odontoblasts leads to aberrant dento-alveolar complex formation.Therefore, appropriate inhibition of Wnt/β-catenin signaling is important for the dento-alveolar complex formation.

View Article: PubMed Central - PubMed

Affiliation: Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences, Chonbuk National University School of Dentistry, Jeonju, Korea.

ABSTRACT
Wnt/β-catenin signaling plays a critical role in bone formation and regeneration. Dentin and cementum share many similarities with bone in their biochemical compositions and biomechanical properties. Whether Wnt/β-catenin signaling is involved in the dento-alveolar complex formation is unknown. To understand the roles of Wnt/β-catenin signaling in the dento-alveolar complex formation, we generated conditional β-catenin activation mice through intercross of Catnb(+/lox(ex3)) mice with Col1a1-cre mice. In mutant mice, tooth formation and eruption was disturbed. Lower incisors and molars did not erupt. Bone formation was increased in the mandible but tooth formation was severely disturbed. Hypomineralized dentin was deposited in the crown but roots of molars were extremely short and distorted. In the odontoblasts of mutant molars, expression of dentin matrix proteins was obviously downregulated following the activation of β-catenin whereas that of mineralization inhibitor was increased. Cementum and periodontal ligament were hypoplastic but periodontal space was narrow due to increased alveolar bone formation. While cementum matrix proteins were decreased, bone matrix proteins were increased in the cementum and alveolar bone of mutant mice. These results indicate that local activation of β-catenin in the osteoblasts and odontoblasts leads to aberrant dento-alveolar complex formation. Therefore, appropriate inhibition of Wnt/β-catenin signaling is important for the dento-alveolar complex formation.

No MeSH data available.


Related in: MedlinePlus

Mineralization defects in dentin of Col1a1-cre:Catnb+/lox(ex3) mice. (A, B) Immunohistochemistry reveal that β-catenin is localized in the Od and pulp cells of mandibular first molar of WT mice, which is restrictedly increased in the odontoblasts of MT mice. (C, D) Phex is localized in the odontoblasts of WT mice, but which is clearly reduced in the odontoblasts of MT mice. (E, F) In WT mice, Dspp is localized in the dentin as well as odontoblasts, but it is obviously decreased in the predentin and odontoblasts of MT mice. Dspp remains only in thin mineralized dentin of MT mice. (G, H) Localization of Fgf23 is not found in the dentin and odontoblasts of WT mice but which is clearly observed in the predentin of MT mice. (I-L) Bgn and Dmp1 are mainly localized in the predentin and a part of dentin in WT mice, which also decreased in the predentin of MT mice. Od, odontoblasts; WT, wild type; MT, mutant; Phex, phosphate regulating endopeptidase homologue on the X chromosome; Dspp, dentin sialophosphoprotein; Fgf23, fibroblast growth factor-23; Bgn, biglycan; Dmp1, dentin matrix protein-1. Scale bar=100 µm (A-L).
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Figure 3: Mineralization defects in dentin of Col1a1-cre:Catnb+/lox(ex3) mice. (A, B) Immunohistochemistry reveal that β-catenin is localized in the Od and pulp cells of mandibular first molar of WT mice, which is restrictedly increased in the odontoblasts of MT mice. (C, D) Phex is localized in the odontoblasts of WT mice, but which is clearly reduced in the odontoblasts of MT mice. (E, F) In WT mice, Dspp is localized in the dentin as well as odontoblasts, but it is obviously decreased in the predentin and odontoblasts of MT mice. Dspp remains only in thin mineralized dentin of MT mice. (G, H) Localization of Fgf23 is not found in the dentin and odontoblasts of WT mice but which is clearly observed in the predentin of MT mice. (I-L) Bgn and Dmp1 are mainly localized in the predentin and a part of dentin in WT mice, which also decreased in the predentin of MT mice. Od, odontoblasts; WT, wild type; MT, mutant; Phex, phosphate regulating endopeptidase homologue on the X chromosome; Dspp, dentin sialophosphoprotein; Fgf23, fibroblast growth factor-23; Bgn, biglycan; Dmp1, dentin matrix protein-1. Scale bar=100 µm (A-L).

Mentions: Immunohistochemistry revealed that β-catenin was localized in the differentiated odontoblasts and pulp cells of the mandibular first molar of WT mice, which is restrictedly increased in the odontoblasts of MT mice (Fig. 3A, B). Phex was localized in the differentiated odontoblasts of WT mice, but was clearly absent in the odontoblasts of MT mice except some cells included in dentin matrix (Fig. 3C, D). Dspp was extensively localized in the dentin matrix and odontoblasts of WT mice. But it was obviously decreased in the odontoblasts and predentin except thin mineralized dentin layer of MT mice (Fig. 3E, F). A mineralization inhibitor, Fgf23 was not localized in the odontoblasts as well as dentin matrix of WT mice. Interestingly, Fgf23 was extensively localized in the predentin layer of MT mice (Fig. 3G, H). Bgn was exclusively localized in the thin predentin layer in WT mice, but was significantly decreased in the MT mice (Fig. 3I, J). Dmp1 was localized in the junction area between dentin and predentin both of WT and MT mice. These results suggest that activation of β-catenin in the odontoblasts may disturb the differentiation of odontoblasts and mineralization of dentin matrix.


Col1a1-cre mediated activation of β-catenin leads to aberrant dento-alveolar complex formation.

Kim TH, Bae CH, Jang EH, Yoon CY, Bae Y, Ko SO, Taketo MM, Cho ES - Anat Cell Biol (2012)

Mineralization defects in dentin of Col1a1-cre:Catnb+/lox(ex3) mice. (A, B) Immunohistochemistry reveal that β-catenin is localized in the Od and pulp cells of mandibular first molar of WT mice, which is restrictedly increased in the odontoblasts of MT mice. (C, D) Phex is localized in the odontoblasts of WT mice, but which is clearly reduced in the odontoblasts of MT mice. (E, F) In WT mice, Dspp is localized in the dentin as well as odontoblasts, but it is obviously decreased in the predentin and odontoblasts of MT mice. Dspp remains only in thin mineralized dentin of MT mice. (G, H) Localization of Fgf23 is not found in the dentin and odontoblasts of WT mice but which is clearly observed in the predentin of MT mice. (I-L) Bgn and Dmp1 are mainly localized in the predentin and a part of dentin in WT mice, which also decreased in the predentin of MT mice. Od, odontoblasts; WT, wild type; MT, mutant; Phex, phosphate regulating endopeptidase homologue on the X chromosome; Dspp, dentin sialophosphoprotein; Fgf23, fibroblast growth factor-23; Bgn, biglycan; Dmp1, dentin matrix protein-1. Scale bar=100 µm (A-L).
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
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Figure 3: Mineralization defects in dentin of Col1a1-cre:Catnb+/lox(ex3) mice. (A, B) Immunohistochemistry reveal that β-catenin is localized in the Od and pulp cells of mandibular first molar of WT mice, which is restrictedly increased in the odontoblasts of MT mice. (C, D) Phex is localized in the odontoblasts of WT mice, but which is clearly reduced in the odontoblasts of MT mice. (E, F) In WT mice, Dspp is localized in the dentin as well as odontoblasts, but it is obviously decreased in the predentin and odontoblasts of MT mice. Dspp remains only in thin mineralized dentin of MT mice. (G, H) Localization of Fgf23 is not found in the dentin and odontoblasts of WT mice but which is clearly observed in the predentin of MT mice. (I-L) Bgn and Dmp1 are mainly localized in the predentin and a part of dentin in WT mice, which also decreased in the predentin of MT mice. Od, odontoblasts; WT, wild type; MT, mutant; Phex, phosphate regulating endopeptidase homologue on the X chromosome; Dspp, dentin sialophosphoprotein; Fgf23, fibroblast growth factor-23; Bgn, biglycan; Dmp1, dentin matrix protein-1. Scale bar=100 µm (A-L).
Mentions: Immunohistochemistry revealed that β-catenin was localized in the differentiated odontoblasts and pulp cells of the mandibular first molar of WT mice, which is restrictedly increased in the odontoblasts of MT mice (Fig. 3A, B). Phex was localized in the differentiated odontoblasts of WT mice, but was clearly absent in the odontoblasts of MT mice except some cells included in dentin matrix (Fig. 3C, D). Dspp was extensively localized in the dentin matrix and odontoblasts of WT mice. But it was obviously decreased in the odontoblasts and predentin except thin mineralized dentin layer of MT mice (Fig. 3E, F). A mineralization inhibitor, Fgf23 was not localized in the odontoblasts as well as dentin matrix of WT mice. Interestingly, Fgf23 was extensively localized in the predentin layer of MT mice (Fig. 3G, H). Bgn was exclusively localized in the thin predentin layer in WT mice, but was significantly decreased in the MT mice (Fig. 3I, J). Dmp1 was localized in the junction area between dentin and predentin both of WT and MT mice. These results suggest that activation of β-catenin in the odontoblasts may disturb the differentiation of odontoblasts and mineralization of dentin matrix.

Bottom Line: Lower incisors and molars did not erupt.These results indicate that local activation of β-catenin in the osteoblasts and odontoblasts leads to aberrant dento-alveolar complex formation.Therefore, appropriate inhibition of Wnt/β-catenin signaling is important for the dento-alveolar complex formation.

View Article: PubMed Central - PubMed

Affiliation: Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences, Chonbuk National University School of Dentistry, Jeonju, Korea.

ABSTRACT
Wnt/β-catenin signaling plays a critical role in bone formation and regeneration. Dentin and cementum share many similarities with bone in their biochemical compositions and biomechanical properties. Whether Wnt/β-catenin signaling is involved in the dento-alveolar complex formation is unknown. To understand the roles of Wnt/β-catenin signaling in the dento-alveolar complex formation, we generated conditional β-catenin activation mice through intercross of Catnb(+/lox(ex3)) mice with Col1a1-cre mice. In mutant mice, tooth formation and eruption was disturbed. Lower incisors and molars did not erupt. Bone formation was increased in the mandible but tooth formation was severely disturbed. Hypomineralized dentin was deposited in the crown but roots of molars were extremely short and distorted. In the odontoblasts of mutant molars, expression of dentin matrix proteins was obviously downregulated following the activation of β-catenin whereas that of mineralization inhibitor was increased. Cementum and periodontal ligament were hypoplastic but periodontal space was narrow due to increased alveolar bone formation. While cementum matrix proteins were decreased, bone matrix proteins were increased in the cementum and alveolar bone of mutant mice. These results indicate that local activation of β-catenin in the osteoblasts and odontoblasts leads to aberrant dento-alveolar complex formation. Therefore, appropriate inhibition of Wnt/β-catenin signaling is important for the dento-alveolar complex formation.

No MeSH data available.


Related in: MedlinePlus