Wnt Signaling Regulates Pulp Volume and Dentin Thickness

Won Hee Lim; Bo Liu; Du Cheng; Daniel J. Hunter; Zhendong Zhong; Daniel M. Ramos; Bart O. Williams; Paul T. Sharpe; Claire Bardet; Su-jung Mah; Jill A. Helms

doi:10.1002/jbmr.2088

Wnt Signaling Regulates Pulp Volume and Dentin Thickness

Won Hee Lim, Bo Liu, Du Cheng, Daniel J. Hunter, Zhendong Zhong, Daniel M. Ramos, Bart O. Williams, Paul T. Sharpe, Claire Bardet, Su-jung Mah, Jill A. Helms^*

^*Corresponding author for this work

Centre for Craniofacial & Regenerative Biology

Research output: Contribution to journal › Article › peer-review

46 Citations (Scopus)

Abstract

Odontoblasts, cementoblasts, ameloblasts, and osteoblasts all form mineralized tissues in the craniofacial complex, and all these cell types exhibit active Wnt signaling during postnatal life. We set out to understand the functions of this Wnt signaling, by evaluating the phenotypes of mice in which the essential Wnt chaperone protein, Wntless was eliminated. The deletion of Wls was restricted to cells expressing Osteocalcin (OCN), which in addition to osteoblasts includes odontoblasts, cementoblasts, and ameloblasts. Dentin, cementum, enamel, and bone all formed in OCN‐Cre;Wls fl/fl mice but their homeostasis was dramatically affected. The most notable feature was a significant increase in dentin volume and density. We attribute this gain in dentin volume to a Wnt‐mediated misregulation of Runx2. Normally, Wnt signaling stimulates Runx2, which in turn inhibits dentin sialoprotein (DSP); this inhibition must be relieved for odontoblasts to differentiate. In OCN‐Cre;Wls fl/fl mice, Wnt pathway activation is reduced and Runx2 levels decline. The Runx2‐mediated repression of DSP is relieved and odontoblast differentiation is accordingly enhanced. This study demonstrates the importance of Wnt signaling in the homeostasis of mineralized tissues of the craniofacial complex.

Original language	English
Article number	N/A
Pages (from-to)	892-901
Number of pages	10
Journal	Journal of Bone and Mineral Research
Volume	29
Issue number	4
DOIs	https://doi.org/10.1002/jbmr.2088
Publication status	Published - Apr 2014

Keywords

RECEPTOR-RELATED PROTEIN-5
HIGH-BONE-MASS
TOOTH DEVELOPMENT
GENE-EXPRESSION
UP-REGULATION
BETA-CATENIN
STEM-CELLS
ODONTOBLASTS
MICE
TELOMERASE

Access to Document

10.1002/jbmr.2088

Cite this

@article{ec1e90a474714136a8e7580adca14379,

title = "Wnt Signaling Regulates Pulp Volume and Dentin Thickness",

abstract = "Odontoblasts, cementoblasts, ameloblasts, and osteoblasts all form mineralized tissues in the craniofacial complex, and all these cell types exhibit active Wnt signaling during postnatal life. We set out to understand the functions of this Wnt signaling, by evaluating the phenotypes of mice in which the essential Wnt chaperone protein, Wntless was eliminated. The deletion of Wls was restricted to cells expressing Osteocalcin (OCN), which in addition to osteoblasts includes odontoblasts, cementoblasts, and ameloblasts. Dentin, cementum, enamel, and bone all formed in OCN‐Cre;Wls fl/fl mice but their homeostasis was dramatically affected. The most notable feature was a significant increase in dentin volume and density. We attribute this gain in dentin volume to a Wnt‐mediated misregulation of Runx2. Normally, Wnt signaling stimulates Runx2, which in turn inhibits dentin sialoprotein (DSP); this inhibition must be relieved for odontoblasts to differentiate. In OCN‐Cre;Wls fl/fl mice, Wnt pathway activation is reduced and Runx2 levels decline. The Runx2‐mediated repression of DSP is relieved and odontoblast differentiation is accordingly enhanced. This study demonstrates the importance of Wnt signaling in the homeostasis of mineralized tissues of the craniofacial complex.",

keywords = "RECEPTOR-RELATED PROTEIN-5, HIGH-BONE-MASS, TOOTH DEVELOPMENT, GENE-EXPRESSION, UP-REGULATION, BETA-CATENIN, STEM-CELLS, ODONTOBLASTS, MICE, TELOMERASE",

author = "Lim, {Won Hee} and Bo Liu and Du Cheng and Hunter, {Daniel J.} and Zhendong Zhong and Ramos, {Daniel M.} and Williams, {Bart O.} and Sharpe, {Paul T.} and Claire Bardet and Su-jung Mah and Helms, {Jill A.}",

year = "2014",

month = apr,

doi = "10.1002/jbmr.2088",

language = "English",

volume = "29",

pages = "892--901",

journal = "Journal of Bone and Mineral Research",

issn = "0884-0431",

publisher = "Wiley-Blackwell",

number = "4",

}

TY - JOUR

T1 - Wnt Signaling Regulates Pulp Volume and Dentin Thickness

AU - Lim, Won Hee

AU - Liu, Bo

AU - Cheng, Du

AU - Hunter, Daniel J.

AU - Zhong, Zhendong

AU - Ramos, Daniel M.

AU - Williams, Bart O.

AU - Sharpe, Paul T.

AU - Bardet, Claire

AU - Mah, Su-jung

AU - Helms, Jill A.

PY - 2014/4

Y1 - 2014/4

N2 - Odontoblasts, cementoblasts, ameloblasts, and osteoblasts all form mineralized tissues in the craniofacial complex, and all these cell types exhibit active Wnt signaling during postnatal life. We set out to understand the functions of this Wnt signaling, by evaluating the phenotypes of mice in which the essential Wnt chaperone protein, Wntless was eliminated. The deletion of Wls was restricted to cells expressing Osteocalcin (OCN), which in addition to osteoblasts includes odontoblasts, cementoblasts, and ameloblasts. Dentin, cementum, enamel, and bone all formed in OCN‐Cre;Wls fl/fl mice but their homeostasis was dramatically affected. The most notable feature was a significant increase in dentin volume and density. We attribute this gain in dentin volume to a Wnt‐mediated misregulation of Runx2. Normally, Wnt signaling stimulates Runx2, which in turn inhibits dentin sialoprotein (DSP); this inhibition must be relieved for odontoblasts to differentiate. In OCN‐Cre;Wls fl/fl mice, Wnt pathway activation is reduced and Runx2 levels decline. The Runx2‐mediated repression of DSP is relieved and odontoblast differentiation is accordingly enhanced. This study demonstrates the importance of Wnt signaling in the homeostasis of mineralized tissues of the craniofacial complex.

AB - Odontoblasts, cementoblasts, ameloblasts, and osteoblasts all form mineralized tissues in the craniofacial complex, and all these cell types exhibit active Wnt signaling during postnatal life. We set out to understand the functions of this Wnt signaling, by evaluating the phenotypes of mice in which the essential Wnt chaperone protein, Wntless was eliminated. The deletion of Wls was restricted to cells expressing Osteocalcin (OCN), which in addition to osteoblasts includes odontoblasts, cementoblasts, and ameloblasts. Dentin, cementum, enamel, and bone all formed in OCN‐Cre;Wls fl/fl mice but their homeostasis was dramatically affected. The most notable feature was a significant increase in dentin volume and density. We attribute this gain in dentin volume to a Wnt‐mediated misregulation of Runx2. Normally, Wnt signaling stimulates Runx2, which in turn inhibits dentin sialoprotein (DSP); this inhibition must be relieved for odontoblasts to differentiate. In OCN‐Cre;Wls fl/fl mice, Wnt pathway activation is reduced and Runx2 levels decline. The Runx2‐mediated repression of DSP is relieved and odontoblast differentiation is accordingly enhanced. This study demonstrates the importance of Wnt signaling in the homeostasis of mineralized tissues of the craniofacial complex.

KW - RECEPTOR-RELATED PROTEIN-5

KW - HIGH-BONE-MASS

KW - TOOTH DEVELOPMENT

KW - GENE-EXPRESSION

KW - UP-REGULATION

KW - BETA-CATENIN

KW - STEM-CELLS

KW - ODONTOBLASTS

KW - MICE

KW - TELOMERASE

U2 - 10.1002/jbmr.2088

DO - 10.1002/jbmr.2088

M3 - Article

SN - 0884-0431

VL - 29

SP - 892

EP - 901

JO - Journal of Bone and Mineral Research

JF - Journal of Bone and Mineral Research

IS - 4

M1 - N/A

ER -

Wnt Signaling Regulates Pulp Volume and Dentin Thickness

Abstract

Keywords

Access to Document

Fingerprint

Cite this