Differentiating dental pulp cells via RGD-dendrimer conjugates

J Dent Res. 2010 Dec;89(12):1433-8. doi: 10.1177/0022034510384870. Epub 2010 Oct 6.

Abstract

Traumatic dental injuries are often irreversible, underscoring the need for therapies that protect dental pulp cells and enhance their regeneration. We hypothesized that generation 5 poly amido amine (PAMAM) dendrimers (G5), functionalized with fluorescein isothiocyanate (FL) and αVβ3-specific, cyclic arginine-glycine-aspartic acid (RGD) peptides, will bind to dental pulp cells (DPCs) and modulate their differentiation. Dental pulp cells and mouse odontoblast-like cells (MDPC-23) (±) treated with G5-FL-RGD were analyzed via Western blot, RT-PCR, and quantitative PCR. Transcription of dental differentiation markers was as follows: Dentin matrix protein (DMP-1), dentin sialoprotein (DSPP), and matrix extracellular phosphoglycoprotein (MEPE) as well as vascular endothelial growth factor (VEGF) all increased via the JNK pathway. Long-term G5-RGD treatment of dental pulp cells resulted in enhanced mineralization as examined via Von Kossa assay, suggesting that PAMAM dendrimers conjugated to cyclic RGD peptides can increase the odontogenic potential of these cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Animals
  • Blotting, Western
  • Cell Differentiation / drug effects
  • Cell Line
  • Cells, Cultured
  • Dendrimers / pharmacology*
  • Dental Pulp / cytology
  • Dental Pulp / drug effects*
  • Enamel Organ / cytology
  • Enamel Organ / drug effects
  • Extracellular Matrix Proteins / analysis
  • Fluorescein-5-isothiocyanate
  • Fluorescent Dyes
  • Glycoproteins / analysis
  • Humans
  • Integrin alphaVbeta3 / analysis
  • JNK Mitogen-Activated Protein Kinases / analysis
  • Mice
  • Odontoblasts / cytology
  • Odontoblasts / drug effects
  • Odontogenesis / drug effects
  • Oligopeptides / pharmacology*
  • Phosphoproteins / analysis
  • Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sialoglycoproteins / analysis
  • Tissue Culture Techniques
  • Tooth Calcification / drug effects
  • Vascular Endothelial Growth Factor A / analysis

Substances

  • DMP1 protein, human
  • Dendrimers
  • Extracellular Matrix Proteins
  • Fluorescent Dyes
  • Glycoproteins
  • Integrin alphaVbeta3
  • MEPE protein, human
  • Oligopeptides
  • PAMAM Starburst
  • Phosphoproteins
  • Sialoglycoproteins
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • dentin sialophosphoprotein
  • arginyl-glycyl-aspartic acid
  • JNK Mitogen-Activated Protein Kinases
  • Fluorescein-5-isothiocyanate