Basic fibroblast growth factor inhibits mineralization but induces neuronal differentiation by human dental pulp stem cells through a FGFR and PLCγ signaling pathway

J Cell Biochem. 2011 Jul;112(7):1807-16. doi: 10.1002/jcb.23097.

Abstract

Basic fibroblast growth factor (basic FGF) has pivotal roles in the function of various cell types. Here, we report the effects of basic FGF in the regulation of dental pulp stem cell (DPSC) behaviors including maintaining stemness and directing differentiation. Cells isolated from human dental pulp tissues exhibited stem cell properties including the expression of mRNA markers for embryonic and mesenchymal stem cells, the expression of Stro-1, and the multipotential differentiation. Basic FGF stimulated colony-forming units of DPSCs and up-regulated the expression of the embryonic stem cell markers; Oct4, Rex-1, and Nanog. Moreover, osteogenic medium containing basic FGF inhibited alkaline phosphatase enzymatic activity and mineralization of DPSCs. On the contrary, basic FGF appeared to be an influential growth factor in the neurogenic differentiation of DPSCs. In the presence of basic FGF, increased DPSCs neurosphere size and the up-regulation of neurogenic markers were noted. Inhibitors of FGFR or PLCγ were able to ablate the basic FGF-induced neuronal differentiation of DPSCs. Taken together, these results suggest basic FGF may be involved in the mechanisms controlling DPSCs cell fate decisions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Adult Stem Cells / cytology*
  • Adult Stem Cells / drug effects
  • Alkaline Phosphatase / metabolism
  • Anthraquinones
  • Antigens, Differentiation / genetics
  • Antigens, Differentiation / metabolism
  • Calcification, Physiologic / drug effects*
  • Cell Differentiation
  • Cell Shape
  • Cells, Cultured
  • Colony-Forming Units Assay
  • Coloring Agents
  • Dental Pulp / cytology*
  • Enzyme Assays
  • Fibroblast Growth Factor 2 / pharmacology
  • Fibroblast Growth Factor 2 / physiology*
  • Humans
  • Neurons / cytology*
  • Neurons / drug effects
  • Osteoblasts / cytology
  • Osteoblasts / metabolism
  • Phospholipase C gamma / metabolism*
  • Receptors, Fibroblast Growth Factor / metabolism*
  • Signal Transduction*
  • Transcription, Genetic

Substances

  • Anthraquinones
  • Antigens, Differentiation
  • Coloring Agents
  • Receptors, Fibroblast Growth Factor
  • Fibroblast Growth Factor 2
  • alizarin
  • Alkaline Phosphatase
  • Phospholipase C gamma