New Roles and Mechanism of Action of BMP4 in Postnatal Tooth Cytodifferentiation

Bone. 2010 Jun;46(6):1533-45. doi: 10.1016/j.bone.2010.02.024. Epub 2010 Mar 3.

Abstract

During the phase of overt tooth cytodifferentiation that occurs after birth in the mouse and using the 3.6Collagen1a-Cre and the BMP4 floxed and BMP4 knockout mice, the BMP4 gene was deleted in early collagen producing odontoblasts around postnatal day 1. BMP4 expression was reduced over 90% in alveolar osteoblasts and odontoblasts. There was decreased rate of predentin to dentin formation and decreased mature odontoblast differentiation reflected in reduced DMP1 expression and proper dentinal tubule formation, as well as reduced Collagen type I and Osteocalcin expression. We observed mutant dysmorphogenic odontoblasts that failed to properly elongate and differentiate. The consequence of this failed differentiation process leads to permanent loss of dentin thickness, apparent enlarged pulp chambers in the molars and reduced bone supporting the tooth structures in mice as old as 10-12 months. Deletion of the BMP4 gene in odontoblasts also indirectly disrupted the process of enamel formation that persisted throughout life. The mechanism for this altered differentiation program in the absence of the BMP4 gene in odontoblasts is from decreased BMP signaling, and decreased expression of three key transcription factors, Dlx3, Dlx5, and Osterix. BMP signaling, as well as Dlx3 and Amelogenin expression, is also indirectly reduced in the ameloblasts of the odontoblast BMP4 cKO mice. This supports a key paracrine or endocrine postnatal role of odontoblast derived BMP4 on the proper amelogenesis and formation of the enamel.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Ameloblasts / cytology
  • Ameloblasts / metabolism
  • Amelogenin / genetics
  • Animals
  • Bone Morphogenetic Protein 4 / genetics
  • Bone Morphogenetic Protein 4 / metabolism*
  • Cell Differentiation / genetics
  • Cell Differentiation / physiology*
  • Dental Enamel / metabolism
  • Homeodomain Proteins / genetics
  • Immunohistochemistry
  • In Situ Hybridization
  • Mice
  • Mice, Knockout
  • Odontoblasts / cytology
  • Odontoblasts / metabolism
  • Osteoblasts / cytology
  • Osteoblasts / metabolism
  • Tooth / cytology*
  • Tooth / metabolism*
  • Transcription Factors / genetics

Substances

  • Amelogenin
  • Bone Morphogenetic Protein 4
  • Distal-less homeobox proteins
  • Homeodomain Proteins
  • Transcription Factors