Prolyl hydroxylase inhibitors increase the production of vascular endothelial growth factor in dental pulp-derived cells

J Endod. 2012 Nov;38(11):1498-503. doi: 10.1016/j.joen.2012.08.003. Epub 2012 Sep 18.


Introduction: Prolyl hydroxylase (PHD) inhibitors can induce a proangiogenic response that stimulates regeneration in soft and hard tissues. However, the effect of PHD inhibitors on the dental pulp is unclear. The purpose of this study was to evaluate the effects of PHD inhibitors on the proangiogenic capacity of human dental pulp-derived cells.

Methods: To test the response of dental pulp-derived cells to PHD inhibitors, the cells were exposed to dimethyloxalylglycine, desferrioxamine, L-mimosine, and cobalt chloride. To assess the response of dental pulp cells to a capping material supplemented with PHD inhibitors, the cells were treated with supernatants from calcium hydroxide. Viability, proliferation, and protein synthesis were assessed by formazan formation, (3)[H]thymidine, and (3)[H]leucine incorporation assays. The effect on the proangiogenic capacity was measured by immunoassays for vascular endothelial growth factor (VEGF).

Results: We found that all 4 PHD inhibitors can reduce viability, proliferation, and protein synthesis at high concentrations. At nontoxic concentrations and in the presence of supernatants from calcium hydroxide, PHD inhibitors stimulated the production of VEGF in dental pulp-derived cells. When calcium hydroxide was supplemented with the PHD inhibitors, the supernatants from these preparations did not significantly elevate VEGF levels.

Conclusions: These results show that PHD inhibitors can stimulate VEGF production of dental pulp-derived cells, suggesting a corresponding increase in their proangiogenic capacity. Further studies will be required to understand the impact that this might have on pulp regeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids, Dicarboxylic / pharmacology
  • Cells, Cultured
  • Cobalt / pharmacology
  • Deferoxamine / pharmacology
  • Dental Pulp / cytology
  • Dental Pulp / drug effects*
  • Dental Pulp / metabolism*
  • Dental Pulp Capping
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Mimosine / pharmacokinetics
  • Mimosine / pharmacology
  • Neovascularization, Physiologic / drug effects*
  • Procollagen-Proline Dioxygenase / antagonists & inhibitors*
  • Regeneration / drug effects
  • Siderophores / pharmacology
  • Vascular Endothelial Growth Factor A / biosynthesis*


  • Amino Acids, Dicarboxylic
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Siderophores
  • Vascular Endothelial Growth Factor A
  • Cobalt
  • Mimosine
  • Procollagen-Proline Dioxygenase
  • cobaltous chloride
  • Deferoxamine
  • oxalylglycine