Simvastatin promotes odontoblastic differentiation and expression of angiogenic factors via heme oxygenase-1 in primary cultured human dental pulp cells.
BACKGROUND
Although simvastatin has multiple demonstrable effects, its function in dentinogenesis remains unclear. In this study, we tested the hypothesis that the addition of simvastatin to human dental pulp cells (HDPCs) stimulates odontogenesis both by promoting odontoblastic differentiation and by favoring the release of angiogenic factors. In addition, the role of heme oxygenase-1 (HO-1) in these effects was investigated.


METHODS
The expression of markers for odontoblastic differentiation and angiogenesis was analyzed by means of alkaline phosphatase (ALP) activity, alizarin red staining, and Western blotting.


RESULTS
Simvastatin enhanced the differentiation of HDPCs by up-regulating mineralization nodules and odontogenic markers as well as angiogenic markers. These phenomena were then correlated with the induction of HO-1 protein levels. The inducing effect of simvastatin on odontoblastic differentiation and angiogenesis was nullified by an HO-1 inhibitor and a carbon monoxide (CO) scavenger.


CONCLUSIONS
These results suggested that simvastatin exerts its odontoblastic differentiation and angiogenesis-inducing effects in HDPCs through a mechanism that involves the action of HO-1 and its product CO.
Min
Kyung-San
KS
Department of Conservative Dentistry, School of Dentistry, Wonkwang University, Iksan, Jeonbuk, Republic of Korea.
Lee
Young-Man
YM
Hong
Sung-Ok
SO
Kim
Eun-Cheol
EC
D000704:Analysis of Variance; D042501:Angiogenic Proteins / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003782:Dental Pulp / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D003810:Dentinogenesis / Q000187:drug effects / Q000502:physiology; D051547:Heme Oxygenase-1 / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D009804:Odontoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019821:Simvastatin / Q000494:pharmacology*; D018709:Statistics, Nonparametric
D042501:Angiogenic Proteins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin; D051547:Heme Oxygenase-1