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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

Deformities in the roots and periodontium of Col1a1-cre:Catnb+/lox(ex3) mice. (A, B) In contrast to WT mice, RD is thin and hypomineralized in MT mice. In addition, PS is narrower due to excessive formation of alveolar bone in MT mice. (C, D) In the RD of MT mice, Dspp is decreased in the dentin. (E-J) In WT mice, Bsp, Dmp1 and Fgf23 are specifically localized in the matrix of acellular cementum (arrows) and alveolar bone, which is decreased in the MT mice. (K, L) Osteopontin is localized in the cementum and periodontal ligaments of WT mice. It is also decreased in the cementum and periodontal ligaments of MT mice. WT, wild type; RD, root dentin; H&E, hematoxylin and eosin; MT, mutant; PS, periodontal space; Dspp, dentin sialophosphoprotein; Bsp, bone sialoprotein; Dmp1, dentin matrix protein-1; Fgf23, fibroblast growth factor-23; Opn, osteopontin. Scale bar=50 µm (A-L).
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Figure 4: Deformities in the roots and periodontium of Col1a1-cre:Catnb+/lox(ex3) mice. (A, B) In contrast to WT mice, RD is thin and hypomineralized in MT mice. In addition, PS is narrower due to excessive formation of alveolar bone in MT mice. (C, D) In the RD of MT mice, Dspp is decreased in the dentin. (E-J) In WT mice, Bsp, Dmp1 and Fgf23 are specifically localized in the matrix of acellular cementum (arrows) and alveolar bone, which is decreased in the MT mice. (K, L) Osteopontin is localized in the cementum and periodontal ligaments of WT mice. It is also decreased in the cementum and periodontal ligaments of MT mice. WT, wild type; RD, root dentin; H&E, hematoxylin and eosin; MT, mutant; PS, periodontal space; Dspp, dentin sialophosphoprotein; Bsp, bone sialoprotein; Dmp1, dentin matrix protein-1; Fgf23, fibroblast growth factor-23; Opn, osteopontin. Scale bar=50 µm (A-L).

Mentions: As described previously, molar roots were short and periodontium was defectively formed in the MT mice. In contrast to WT mice, root dentin was thin and hypomineralized in the MT mice. In addition, periodontal space was narrower due to excessively formed alveolar bone in the MT mice (Fig. 4A, B). In the root dentin of MT mice, Dspp was decreased in the dentin (Fig. 4C, D). In the WT mice, Bsp, Dmp1 and Fgf23 are specifically localized in the matrix of acellular cementum and alveolar bone, which was decreased in the MT mice (Fig. 4E-J). Opn was localized in the cementum and periodontal ligaments of WT mice, but it was also decreased in the cementum and periodontal ligaments of MT mice. From these results, it is suggested that activation of β-catenin in the osteoblasts and cells of periodontium may cause to increase bone formation and root deformities.


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)

Deformities in the roots and periodontium of Col1a1-cre:Catnb+/lox(ex3) mice. (A, B) In contrast to WT mice, RD is thin and hypomineralized in MT mice. In addition, PS is narrower due to excessive formation of alveolar bone in MT mice. (C, D) In the RD of MT mice, Dspp is decreased in the dentin. (E-J) In WT mice, Bsp, Dmp1 and Fgf23 are specifically localized in the matrix of acellular cementum (arrows) and alveolar bone, which is decreased in the MT mice. (K, L) Osteopontin is localized in the cementum and periodontal ligaments of WT mice. It is also decreased in the cementum and periodontal ligaments of MT mice. WT, wild type; RD, root dentin; H&E, hematoxylin and eosin; MT, mutant; PS, periodontal space; Dspp, dentin sialophosphoprotein; Bsp, bone sialoprotein; Dmp1, dentin matrix protein-1; Fgf23, fibroblast growth factor-23; Opn, osteopontin. 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 4: Deformities in the roots and periodontium of Col1a1-cre:Catnb+/lox(ex3) mice. (A, B) In contrast to WT mice, RD is thin and hypomineralized in MT mice. In addition, PS is narrower due to excessive formation of alveolar bone in MT mice. (C, D) In the RD of MT mice, Dspp is decreased in the dentin. (E-J) In WT mice, Bsp, Dmp1 and Fgf23 are specifically localized in the matrix of acellular cementum (arrows) and alveolar bone, which is decreased in the MT mice. (K, L) Osteopontin is localized in the cementum and periodontal ligaments of WT mice. It is also decreased in the cementum and periodontal ligaments of MT mice. WT, wild type; RD, root dentin; H&E, hematoxylin and eosin; MT, mutant; PS, periodontal space; Dspp, dentin sialophosphoprotein; Bsp, bone sialoprotein; Dmp1, dentin matrix protein-1; Fgf23, fibroblast growth factor-23; Opn, osteopontin. Scale bar=50 µm (A-L).
Mentions: As described previously, molar roots were short and periodontium was defectively formed in the MT mice. In contrast to WT mice, root dentin was thin and hypomineralized in the MT mice. In addition, periodontal space was narrower due to excessively formed alveolar bone in the MT mice (Fig. 4A, B). In the root dentin of MT mice, Dspp was decreased in the dentin (Fig. 4C, D). In the WT mice, Bsp, Dmp1 and Fgf23 are specifically localized in the matrix of acellular cementum and alveolar bone, which was decreased in the MT mice (Fig. 4E-J). Opn was localized in the cementum and periodontal ligaments of WT mice, but it was also decreased in the cementum and periodontal ligaments of MT mice. From these results, it is suggested that activation of β-catenin in the osteoblasts and cells of periodontium may cause to increase bone formation and root deformities.

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