Effect of tyrosine-rich amelogenin peptide on behavior and differentiation of endothelial cells

Clin Oral Investig. 2016 Nov;20(8):2275-2284. doi: 10.1007/s00784-016-1726-2. Epub 2016 Feb 12.


Background: Enamel matrix derivative (EMD) is an effective biomaterial for periodontal tissue regeneration and might stimulate angiogenesis. Tyrosine-rich amelogenin peptide (TRAP) is present in EMD and is thought to contribute in its biological activity. In the present study, we investigated the effect of chemically synthesized TRAP on proliferation, migration, angiogenic structure formation, and differentiation of human umbilical vein endothelial cells (HUVECs) in vitro.

Material and methods: The effects of TRAP isolated from EMD and chemically synthesized TRAP on proliferation/viability, migration, and angiogenic structure formation were investigated. Expression of angiopoietin-2 (ang-2), von Willebrand factor (vWF), E-selectin, intracellular adhesion molecules 1 (ICAM-1), vascular endothelial growth factor (VEGF) receptors FMS-like tyrosine kinase 1 (FLT-1), and kinase insert domain receptor (KDR) was measured on both messenger RNA (mRNA) and protein levels.

Results: The proliferation/viability of HUVECs was inhibited by TRAP at concentration of 100 μg/ml and slightly stimulated by EMD at similar concentration. Both EMD and TRAP stimulated endothelial cell migration in microchemotaxis chamber. The effect of both TRAP preparations on the migration was significantly higher than that of EMD. All substances stimulated formation of angiogenic structure in vitro. The expression of ICAM-1, E-selectin, FLT-1, KDR, and vWF was significantly increased by both TRAP and EMD at a concentration 50 μg/ml. The expression of ang-2 was not affected by TRAP but was significantly increased by EMD.

Conclusion: Our in vitro study shows that TRAP confer the most effects of EMD on the endothelial cells.

Clinical relevance: TRAP might be used as a basis for development of new approaches for periodontal regeneration.

Keywords: Angiogenesis; Enamel matrix derivative; Endothelial cells; Wound healing.

MeSH terms

  • Amelogenin / pharmacology*
  • Biomarkers / analysis
  • Cell Differentiation / drug effects*
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Dental Enamel Proteins / pharmacology*
  • Endothelial Cells / drug effects*
  • Humans
  • In Vitro Techniques
  • Neovascularization, Pathologic
  • Tyrosine / pharmacology*
  • Umbilical Veins / cytology


  • Amelogenin
  • Biomarkers
  • Dental Enamel Proteins
  • enamel matrix proteins
  • Tyrosine