Disruption of Wnt/β-catenin signaling in odontoblasts and cementoblasts arrests tooth root development in postnatal mouse teeth

Int J Biol Sci. 2013;9(3):228-36. doi: 10.7150/ijbs.5476. Epub 2013 Feb 19.

Abstract

Tooth development undergoes a series of complex reciprocal interactions between dental epithelium and the underlying mesenchymal cells. Compared with the study in tooth crown formation, little is known about the molecular mechanism underlying the development of tooth roots. In the present study, we conditionally knock out β-catenin gene (Ctnnb1) within developing odontoblasts and cementoblasts during the development of tooth roots, and observed rootless molars as well as incomplete incisors. Histological analyses revealed intact structure of molar crown and labial side of incisor, however, as for the molar roots and the lingual portion of incisor, the formation of dentin and periodontal tissues were greatly hampered. In situ hybridization experiments using probes of odontoblastic marker genes collagen type I, alpha 1 (Col1a1), osteocalcin (OC) and dentin sialophosphoprotein (Dspp) manifested striking undifferentiation of root odontoblasts in which Ctnnb1 was eliminated. Bromodeoxyuridine (BrdU) labeling and proliferating cell nuclear antigen (PCNA) immunohistochemical experiments also showed retarded proliferation of pre-odontoblasts in mutant mice. However, cell apoptosis was not affected. Additionally, a disrupted formation of cementoblasts, suggested by the absence of transcripts of bone sialoprotein (Bsp) in follicle mesenchyme, was also evident in mutant mice. Our study provides strong in vivo evidence to confirm that Wnt/β-catenin signaling is functionally significant to root odontogenesis and cementogenesis during the tooth root development.

Keywords: Odontoblast; Tooth root development; Wnt/β-catenin signaling; mouse model..

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Cell Differentiation
  • Cell Proliferation
  • Dental Cementum / metabolism*
  • Dental Cementum / pathology
  • Dentin / metabolism
  • Gene Knockout Techniques
  • Incisor / growth & development
  • Incisor / pathology
  • Mice
  • Mice, Transgenic
  • Odontoblasts / metabolism*
  • Odontoblasts / pathology
  • Tooth Root / growth & development*
  • Tooth Root / pathology
  • Wnt Signaling Pathway / physiology*
  • beta Catenin / genetics

Substances

  • CTNNB1 protein, mouse
  • beta Catenin