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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

Molecular changes related with increased bone mass in the mandibles of Col1a1-cre:Catnb+/lox(ex3) mice. (A, B) In the mandible of MT mice, bone mass is increased but number of osteoblasts are decreased to compare with those of WT mice. (C-F) Bsp expression is slightly increased with increase of bone mass, but Tnap is clearly decreased in the MT. (G-J) Bgn is significantly increased in the mandible of MT mice, while Phex is almost disappeared in MT mice. (K, L) Increased expression of Dmp1 is also observed in MT mice. WT, wild type; H&E, hamatoxylin and eosin; MT, mutant; Bsp, bone sialoprotein; Tnap, tissue-nonspecific alkaline phosphatase; Bgn, biglycan; Phex, phosphate regulating endopeptidase homologue on the X chromosome; Dmp1, dentin matrix protein-1. Scale bar=50 µm (A-L).
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Figure 5: Molecular changes related with increased bone mass in the mandibles of Col1a1-cre:Catnb+/lox(ex3) mice. (A, B) In the mandible of MT mice, bone mass is increased but number of osteoblasts are decreased to compare with those of WT mice. (C-F) Bsp expression is slightly increased with increase of bone mass, but Tnap is clearly decreased in the MT. (G-J) Bgn is significantly increased in the mandible of MT mice, while Phex is almost disappeared in MT mice. (K, L) Increased expression of Dmp1 is also observed in MT mice. WT, wild type; H&E, hamatoxylin and eosin; MT, mutant; Bsp, bone sialoprotein; Tnap, tissue-nonspecific alkaline phosphatase; Bgn, biglycan; Phex, phosphate regulating endopeptidase homologue on the X chromosome; Dmp1, dentin matrix protein-1. Scale bar=50 µm (A-L).

Mentions: In the mandible of MT mice, trabecular spaces were reduced following increase of bone formation (Fig. 5A, B). Bsp immunoreactivity was increased whereas Tnap was decreased in the MT mice (Fig. 5C-F). Phex was strongly expressed in the bone matrix of WT mice but it was nearly absent in the MT mice (Fig. 5G, H). In the mandible of WT mice, Bgn was weakly expressed around osteoblasts. Increased Bgn immunoreactivities were observed around the osteoblasts and osteocytes in the MT mice (Fig. 5I, J). In addition, Dmp1 immunoreactivity was increased in the MT mice (Fig. 5K, L).


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)

Molecular changes related with increased bone mass in the mandibles of Col1a1-cre:Catnb+/lox(ex3) mice. (A, B) In the mandible of MT mice, bone mass is increased but number of osteoblasts are decreased to compare with those of WT mice. (C-F) Bsp expression is slightly increased with increase of bone mass, but Tnap is clearly decreased in the MT. (G-J) Bgn is significantly increased in the mandible of MT mice, while Phex is almost disappeared in MT mice. (K, L) Increased expression of Dmp1 is also observed in MT mice. WT, wild type; H&E, hamatoxylin and eosin; MT, mutant; Bsp, bone sialoprotein; Tnap, tissue-nonspecific alkaline phosphatase; Bgn, biglycan; Phex, phosphate regulating endopeptidase homologue on the X chromosome; Dmp1, dentin matrix protein-1. Scale bar=50 µm (A-L).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 5: Molecular changes related with increased bone mass in the mandibles of Col1a1-cre:Catnb+/lox(ex3) mice. (A, B) In the mandible of MT mice, bone mass is increased but number of osteoblasts are decreased to compare with those of WT mice. (C-F) Bsp expression is slightly increased with increase of bone mass, but Tnap is clearly decreased in the MT. (G-J) Bgn is significantly increased in the mandible of MT mice, while Phex is almost disappeared in MT mice. (K, L) Increased expression of Dmp1 is also observed in MT mice. WT, wild type; H&E, hamatoxylin and eosin; MT, mutant; Bsp, bone sialoprotein; Tnap, tissue-nonspecific alkaline phosphatase; Bgn, biglycan; Phex, phosphate regulating endopeptidase homologue on the X chromosome; Dmp1, dentin matrix protein-1. Scale bar=50 µm (A-L).
Mentions: In the mandible of MT mice, trabecular spaces were reduced following increase of bone formation (Fig. 5A, B). Bsp immunoreactivity was increased whereas Tnap was decreased in the MT mice (Fig. 5C-F). Phex was strongly expressed in the bone matrix of WT mice but it was nearly absent in the MT mice (Fig. 5G, H). In the mandible of WT mice, Bgn was weakly expressed around osteoblasts. Increased Bgn immunoreactivities were observed around the osteoblasts and osteocytes in the MT mice (Fig. 5I, J). In addition, Dmp1 immunoreactivity was increased in the MT mice (Fig. 5K, L).

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