Effects of fibroblast growth factor-2 on the expression and regulation of chemokines in human dental pulp cells

J Endod. 2010 Nov;36(11):1824-30. doi: 10.1016/j.joen.2010.08.020.

Abstract

Background: Fibroblast growth factor-2 (FGF-2) participates in both hematopoiesis and osteogenesis; however, the effects of FGF-2 on chemokines during odontoblastic differentiation have not been reported. This study investigated whether human dental pulp cells (HDPCs) treated with FGF-2 could express chemokines during differentiation into odontoblastic cells and sought to identify its underlying mechanism of action.

Methods: To analyze differentiation, we measured alkaline phosphatase (ALP) activity, calcified nodule formation by alizarin red staining, and marker RNA (mRNA) expression by reverse-transcriptase polymerase chain reaction (RT-PCR). Expression of chemokines, such as interleukin-6 (IL-6), IL-8, monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), and MIP-3α, were evaluated by RT-PCR.

Results: ALP activity, the mineralization, and mRNA expression for odontoblastic markers were enhanced by FGF-2 in HDPCs. FGF-2 also up-regulated the expression of IL-6, IL-8, MCP-1, MIP-1α, and MIP-3α mRNAs, which were attenuated by inhibitors of p38, ERK1/2 and p38 MAP kinases, protein kinase C, phosphoinositide-3 kinase, and NF-κB.

Conclusion: Taken together, these data suggest that FGF-2 plays a role not only as a differentiation inducing factor in the injury repair processes of pulpal tissue but also as a positive regulator of chemokine expression, which may help in tissue engineering and pulp regeneration using HDPCs. However, the fate of odontoblastic or osteoblastic differentiation, effective local delivery for FGF-2, interaction of chemotatic and odontogenic factors, and other limitations will need to be overcome before a major modality for the treatment of pulp disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase / analysis
  • Anthraquinones
  • Calcification, Physiologic / drug effects
  • Cell Differentiation / drug effects
  • Cell Line
  • Cell Proliferation / drug effects
  • Chemokine CCL2 / analysis
  • Chemokine CCL20 / analysis
  • Chemokine CCL3 / analysis
  • Chemokines / drug effects*
  • Coloring Agents
  • Dental Pulp / cytology
  • Dental Pulp / drug effects*
  • Dental Pulp / immunology
  • Enzyme Inhibitors / pharmacology
  • Fibroblast Growth Factor 2 / pharmacology*
  • Gene Expression Regulation / drug effects
  • Genetic Markers / genetics
  • Humans
  • Interleukin-6 / analysis
  • Interleukin-8 / analysis
  • NF-kappa B / antagonists & inhibitors
  • Odontoblasts / drug effects
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Kinase C / antagonists & inhibitors
  • RNA / analysis
  • Signal Transduction / drug effects
  • Stem Cells / drug effects
  • Up-Regulation / drug effects
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors

Substances

  • Anthraquinones
  • CCL2 protein, human
  • Chemokine CCL2
  • Chemokine CCL20
  • Chemokine CCL3
  • Chemokines
  • Coloring Agents
  • Enzyme Inhibitors
  • Genetic Markers
  • Interleukin-6
  • Interleukin-8
  • NF-kappa B
  • Phosphoinositide-3 Kinase Inhibitors
  • Fibroblast Growth Factor 2
  • alizarin
  • RNA
  • Protein Kinase C
  • p38 Mitogen-Activated Protein Kinases
  • Alkaline Phosphatase