Transforming growth factor beta2 regulates growth and differentiation of pulp cells via ALK5/Smad2/3

J Endod. 2008 Apr;34(4):427-32. doi: 10.1016/j.joen.2008.02.007.

Abstract

Transforming growth factor beta (TGF-beta) may regulate the biological activities of dental pulp cells. We found that human dental pulp cells expressed TGF-beta1, TGF-beta2, and a little amount of TGF-beta3 messenger RNA (mRNA). The exposure of pulp cells to TGF-beta2 induced the phosphorylation of Smad2/3, Smad1/5/8, and extracellular regulated-kinase 1/2 (ERK1/2) as observed by Western blotting. Exposure to TGF-beta2 decreased the alkaline phosphatase (ALP) mRNA expression and enzyme activity. Pretreatment of pulp cells with SB431542 (an inhibitor of TGF-beta ALK-4, ALK-5, and ALK-7 receptors) but not U0126 (a MEK1 inhibitor) prevented the inhibition of viable cell number, ALP activity, and mRNA expression by TGF-beta2 in dental pulp cells. These results suggest that TGF-beta may affect the growth and differentiation of dental pulp cells via an autocrine fashion by activation of the ALK/Smad2/3-signal transduction pathways. TGF-beta2 possibly regulates the differentiation of pulp cell at specific stages synergistically with other factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Benzamides / pharmacology
  • Cell Differentiation
  • Cell Proliferation
  • Dental Pulp / cytology
  • Dental Pulp / metabolism*
  • Dioxoles / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Extracellular Signal-Regulated MAP Kinases / physiology
  • Humans
  • MAP Kinase Kinase Kinases / physiology
  • MAP Kinase Signaling System / physiology*
  • Protein Isoforms
  • Protein Serine-Threonine Kinases / antagonists & inhibitors
  • Protein Serine-Threonine Kinases / metabolism*
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptors, Transforming Growth Factor beta / antagonists & inhibitors
  • Receptors, Transforming Growth Factor beta / metabolism*
  • Smad Proteins, Receptor-Regulated / metabolism*
  • Transforming Growth Factor beta1 / biosynthesis
  • Transforming Growth Factor beta2 / biosynthesis
  • Transforming Growth Factor beta2 / physiology*

Substances

  • 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide
  • Benzamides
  • Dioxoles
  • Enzyme Inhibitors
  • Protein Isoforms
  • Receptors, Transforming Growth Factor beta
  • Smad Proteins, Receptor-Regulated
  • Transforming Growth Factor beta1
  • Transforming Growth Factor beta2
  • Protein Serine-Threonine Kinases
  • Extracellular Signal-Regulated MAP Kinases
  • MAP Kinase Kinase Kinases
  • Receptor, Transforming Growth Factor-beta Type I
  • TGFBR1 protein, human
  • Alkaline Phosphatase