The role of heme oxygenase-1 in the proliferation and odontoblastic differentiation of human dental pulp cells

J Endod. 2010 Aug;36(8):1326-31. doi: 10.1016/j.joen.2010.04.011. Epub 2010 Jun 19.

Abstract

Introduction: It was recently reported that heme oxygenase-1 (HO-1) activity is related to stem cell differentiation; however, the involvement of HO-1 in pulp cell growth and differentiation has not been well explored. The purpose of this study was to investigate the role of HO-1 in the growth and differentiation of human dental pulp cells (HDPCs).

Methods: We evaluated cell growth by MTT assay, mineralization by alizarin red staining, and differentiation marker mRNA expression by reverse transcriptase polymerase chain reaction.

Results: HO-1 induction by cobaltic protoporphyrin IX (CoPP) in HDPCs increased cell growth and mineralization and up-regulated the messenger RNA expression of such odontoblastic markers as alkaline phosphatase, osteopontin, bone sialoprotein, dentin matrix protein-1, and dentin sialophosphoprotein. Carbon monoxide scavenger, iron chelator, HO-1 inhibitor, and HO-1 small interfering RNA (siRNA) attenuated HDPC growth and differentiation.

Conclusions: CoPP treatment results in dental pulp cell proliferation and odontoblast differentiation that appears partly mediated by HO-1. Our results suggest that odontoblastic differentiation and growth are positively regulated by HO-1 induction and negatively regulated by HO-1 inhibition. Thus, pharmacologic HO-1 induction might represent a potent therapeutic approach for pulp capping and the regeneration of HDPCs.

MeSH terms

  • Alkaline Phosphatase / analysis
  • Anthraquinones
  • Calcification, Physiologic / physiology
  • Carbon Monoxide / antagonists & inhibitors
  • Cell Culture Techniques
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Coloring Agents
  • Dental Pulp / cytology*
  • Dental Pulp / drug effects
  • Dental Pulp / enzymology
  • Enzyme Induction
  • Enzyme Inhibitors / pharmacology
  • Extracellular Matrix Proteins / analysis
  • Free Radical Scavengers / pharmacology
  • Heme Oxygenase-1 / antagonists & inhibitors
  • Heme Oxygenase-1 / biosynthesis
  • Heme Oxygenase-1 / physiology*
  • Humans
  • Integrin-Binding Sialoprotein
  • Iron Chelating Agents / pharmacology
  • Metalloporphyrins / pharmacology
  • Odontoblasts / drug effects
  • Odontoblasts / enzymology
  • Odontoblasts / physiology*
  • Osteopontin / analysis
  • Phosphoproteins / analysis
  • Protoporphyrins / pharmacology
  • RNA, Messenger / analysis
  • RNA, Small Interfering / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sialoglycoproteins / analysis
  • Tetrazolium Salts
  • Thiazoles
  • Up-Regulation

Substances

  • Anthraquinones
  • Coloring Agents
  • DMP1 protein, human
  • Enzyme Inhibitors
  • Extracellular Matrix Proteins
  • Free Radical Scavengers
  • IBSP protein, human
  • Integrin-Binding Sialoprotein
  • Iron Chelating Agents
  • Metalloporphyrins
  • Phosphoproteins
  • Protoporphyrins
  • RNA, Messenger
  • RNA, Small Interfering
  • Sialoglycoproteins
  • Tetrazolium Salts
  • Thiazoles
  • dentin sialophosphoprotein
  • Osteopontin
  • alizarin
  • cobaltiprotoporphyrin
  • Carbon Monoxide
  • tin protoporphyrin IX
  • Heme Oxygenase-1
  • Alkaline Phosphatase
  • thiazolyl blue