Prolyl hydroxylase inhibitors increase the production of vascular endothelial growth factor in dental pulp-derived cells.
BACKGROUND
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.
Department of Oral Surgery, Medical University of Vienna, Vienna, Austria.
Heinz-Dieter
HD
Müller
Barbara
B
Cvikl
Reinhard
R
Gruber
Georg
G
Watzek
Hermann
H
Agis
D000600:Amino Acids, Dicarboxylic / Q000494:pharmacology; D002478:Cells, Cultured; D003035:Cobalt / Q000494:pharmacology; D003676:Deferoxamine / Q000494:pharmacology; D003782:Dental Pulp / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D003785:Dental Pulp Capping; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008898:Mimosine / Q000493:pharmacokinetics / Q000494:pharmacology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011393:Procollagen-Proline Dioxygenase / Q000037:antagonists & inhibitors*; D012038:Regeneration / Q000187:drug effects; D017262:Siderophores / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
D000600:Amino Acids, Dicarboxylic; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D017262:Siderophores; D042461:Vascular Endothelial Growth Factor A; D003035:Cobalt; D008898:Mimosine; D011393:Procollagen-Proline Dioxygenase; C018021:cobaltous chloride; D003676:Deferoxamine; C040947:oxalylglycine