Simvastatin Promotes Odontoblastic Differentiation and Expression of Angiogenic Factors via Heme Oxygenase-1 in Primary Cultured Human Dental Pulp Cells

Min, Kyung-San; Lee, Young-Man; Hong, Sung-Ok; Kim, Eun-Cheol

doi:10.1016/j.joen.2009.11.021

« Previous Next »Journal of Endodontics
Volume 36, Issue 3 , Pages 447-452, March 2010

Simvastatin Promotes Odontoblastic Differentiation and Expression of Angiogenic Factors via Heme Oxygenase-1 in Primary Cultured Human Dental Pulp Cells

Kyung-San Min, DDS, PhD
- Department of Conservative Dentistry, School of Dentistry, Wonkwang University, Iksan, Jeonbuk, Republic of Korea
- Drs Min and Lee contributed equally to this article.
Young-Man Lee, MS
- Department of Oral and Maxillofacial Pathology, School of Dentistry, Wonkwang University, Iksan, Jeonbuk, Republic of Korea
- Drs Min and Lee contributed equally to this article.
Sung-Ok Hong, DDS, MS
- Department of Conservative Dentistry, School of Dentistry, Wonkwang University, Iksan, Jeonbuk, Republic of Korea
Eun-Cheol Kim, DDS, PhD
- Department of Oral and Maxillofacial Pathology, School of Dentistry, Wonkwang University, Iksan, Jeonbuk, Republic of Korea
- Address requests for reprints to Dr Eun-Cheol Kim, Department of Oral and Maxillofacial Pathology, School of Dentistry, Wonkwang University, 344-2 Shinyongdong, Iksan, Jeonbuk 579-749, Republic of Korea.

published online 25 January 2010.

Abstract

Introduction

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.

Key Words: Angiogenesis heme oxygenase-1, odontoblastic differentiation, simvastatin