PDGFs regulate tooth germ proliferation and ameloblast differentiation

Arch Oral Biol. 2010 Jun;55(6):426-34. doi: 10.1016/j.archoralbio.2010.03.011. Epub 2010 Apr 14.

Abstract

Objective: The purpose of this study was to elucidate the effects of platelet-derived growth factors (PDGFs) during tooth development, as well as the mechanisms underlying the interactions of growth factors with PDGF signalling during odontogenesis.

Design: We used an ex vivo tooth germ organ culture system and two dental cell lines, SF2 cells and mDP cells, as models of odontogenesis. AG17, a tyrosine kinase inhibitor, was utilised for blocking PDGF receptor signalling. To analyse the expressions of PDGFs, reverse transcriptase (RT)-PCR and immunohistochemistry were performed. Proliferation was examined using a BrdU incorporation assay for the organ cultures and a cell counting kit for the cell lines. The expressions of Fgf2 and ameloblastin were analysed by real-time RT-PCR.

Results: The PDGF ligands PDGF-A and PDGF-B, and their receptors, PDGFRalpha and PDGFRbeta, were expressed throughout the initial stages of tooth development. In the tooth germ organ cultures, PDGF-AA, but not PDGF-BB, accelerated cusp formation. Conversely, AG17 suppressed both growth and cusp formation of tooth germs. Exogenous PDGF-BB promoted mDP cell proliferation. Furthermore, PDGF-AA decreased Fgf2 expression and increased that of ameloblastin, a marker of differentiated ameloblasts.

Conclusion: Our results indicate that PDGFs are involved in initial tooth development and regulate tooth size and shape, as well as ameloblast differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ameloblasts / cytology*
  • Animals
  • Cell Differentiation
  • Cell Line
  • Cell Proliferation
  • Dental Enamel Proteins / biosynthesis
  • Dental Enamel Proteins / genetics
  • Epithelial Cells / cytology
  • Fibroblast Growth Factor 2 / biosynthesis
  • Fibroblast Growth Factor 2 / genetics
  • Gene Expression Regulation, Developmental*
  • Mesoderm / cytology
  • Mice
  • Mice, Inbred ICR
  • Odontogenesis / genetics*
  • Organ Culture Techniques
  • Platelet-Derived Growth Factor / biosynthesis*
  • Platelet-Derived Growth Factor / genetics
  • Platelet-Derived Growth Factor / physiology*
  • Receptors, Platelet-Derived Growth Factor / physiology*
  • Signal Transduction
  • Tooth Crown / growth & development
  • Tooth Germ / cytology*
  • Tooth Germ / embryology

Substances

  • Ambn protein, mouse
  • Dental Enamel Proteins
  • Platelet-Derived Growth Factor
  • Fibroblast Growth Factor 2
  • Receptors, Platelet-Derived Growth Factor