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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

Disturbances in tooth formation and eruption failure of molars in Col1a1-cre:Catnb+/lox(ex3) mice. (A, B) In microradiography, general dimensions of craniofacial skeleton in MT mice are smaller than those in WT littermates. Particularly, mandible of MT is severely retarded and resulted in malocclusion. (C, D) In the mid-sagittal view, mandibular incisor is shorter and smaller than that of WT mice. (E, F) Molars of MT mice are impacted within mandible and root formation is impaired while those of WT mice are normally formed and erupted into the oral cavity. (G, H) In H&E-stained sagittal sections of the mandibles, bone deposition is remarkably increased and molars are not erupted in the MT mice. (I, J) In MT mice, β-catenin expression is upregulated in the odontoblasts and osteoblasts. MT, mutant; WT, wild type; H&E, hematoxylin and eosin. Scale bar=100 µm (G-J).
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Figure 2: Disturbances in tooth formation and eruption failure of molars in Col1a1-cre:Catnb+/lox(ex3) mice. (A, B) In microradiography, general dimensions of craniofacial skeleton in MT mice are smaller than those in WT littermates. Particularly, mandible of MT is severely retarded and resulted in malocclusion. (C, D) In the mid-sagittal view, mandibular incisor is shorter and smaller than that of WT mice. (E, F) Molars of MT mice are impacted within mandible and root formation is impaired while those of WT mice are normally formed and erupted into the oral cavity. (G, H) In H&E-stained sagittal sections of the mandibles, bone deposition is remarkably increased and molars are not erupted in the MT mice. (I, J) In MT mice, β-catenin expression is upregulated in the odontoblasts and osteoblasts. MT, mutant; WT, wild type; H&E, hematoxylin and eosin. Scale bar=100 µm (G-J).

Mentions: In microradiographic examination, general dimensions of craniofacial skeleton in MT mice were smaller than those in WT littermates (Fig. 2A, B). Mandible of MT mice was severely retarded in growth and mal-occluded. In microtomographic view of mid-sagittal sections of mandible, incisors were shorter and smaller than those of WT mice (Fig. 2C, D). In the molars of MT mice, root formation was severely impaired while those of WT mice were normally formed (Fig. 2E, F). In H&E stained sections, deposition of bone matrix was remarkably increased in the mandible, but was poorly mineralized in the MT mice (Fig. 2G, H). In the MT mice, molars with short roots were formed but were not erupted into the oral cavity. Overall dentin was poorly mineralized. In the consecutive sections of MT mice, β-catenin expression was increased in the odontoblasts and osteoblasts (Fig. 2I, J).


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)

Disturbances in tooth formation and eruption failure of molars in Col1a1-cre:Catnb+/lox(ex3) mice. (A, B) In microradiography, general dimensions of craniofacial skeleton in MT mice are smaller than those in WT littermates. Particularly, mandible of MT is severely retarded and resulted in malocclusion. (C, D) In the mid-sagittal view, mandibular incisor is shorter and smaller than that of WT mice. (E, F) Molars of MT mice are impacted within mandible and root formation is impaired while those of WT mice are normally formed and erupted into the oral cavity. (G, H) In H&E-stained sagittal sections of the mandibles, bone deposition is remarkably increased and molars are not erupted in the MT mice. (I, J) In MT mice, β-catenin expression is upregulated in the odontoblasts and osteoblasts. MT, mutant; WT, wild type; H&E, hematoxylin and eosin. Scale bar=100 µm (G-J).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3472146&req=5

Figure 2: Disturbances in tooth formation and eruption failure of molars in Col1a1-cre:Catnb+/lox(ex3) mice. (A, B) In microradiography, general dimensions of craniofacial skeleton in MT mice are smaller than those in WT littermates. Particularly, mandible of MT is severely retarded and resulted in malocclusion. (C, D) In the mid-sagittal view, mandibular incisor is shorter and smaller than that of WT mice. (E, F) Molars of MT mice are impacted within mandible and root formation is impaired while those of WT mice are normally formed and erupted into the oral cavity. (G, H) In H&E-stained sagittal sections of the mandibles, bone deposition is remarkably increased and molars are not erupted in the MT mice. (I, J) In MT mice, β-catenin expression is upregulated in the odontoblasts and osteoblasts. MT, mutant; WT, wild type; H&E, hematoxylin and eosin. Scale bar=100 µm (G-J).
Mentions: In microradiographic examination, general dimensions of craniofacial skeleton in MT mice were smaller than those in WT littermates (Fig. 2A, B). Mandible of MT mice was severely retarded in growth and mal-occluded. In microtomographic view of mid-sagittal sections of mandible, incisors were shorter and smaller than those of WT mice (Fig. 2C, D). In the molars of MT mice, root formation was severely impaired while those of WT mice were normally formed (Fig. 2E, F). In H&E stained sections, deposition of bone matrix was remarkably increased in the mandible, but was poorly mineralized in the MT mice (Fig. 2G, H). In the MT mice, molars with short roots were formed but were not erupted into the oral cavity. Overall dentin was poorly mineralized. In the consecutive sections of MT mice, β-catenin expression was increased in the odontoblasts and osteoblasts (Fig. 2I, J).

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