Effect of verapamil, a calcium channel blocker, on the odontogenic activity of human dental pulp cells cultured with silicate-based materials

J Endod. 2014 Aug;40(8):1105-11. doi: 10.1016/j.joen.2013.12.019. Epub 2014 Feb 7.

Abstract

Introduction: This study examines how calcium silicate cement extracts influence the behavior of human dental pulp cells (hDPCs) through calcium channels and active mitogen-activated protein kinase pathways, in particular extracellular signal-related kinase (ERK).

Methods: HDPCs are treated with various silicon concentrations both with and without verapamil, after which the cells' viability and odontogenic differentiation markers are determined by using PrestoBlue assay and Western blot, respectively.

Results: The silicon promoted cell proliferation and inhibited calcium channel blockers. It was also found that silicon increased ERK and p38 activity in a dose-dependent manner. Furthermore, it raised the expression and secretion of alkaline phosphatase, osteocalcin, dentin sialophosphoprotein, and dentin matrix protein-1. In addition, statistically significant differences (P < .05) have been found in the secretion of osteocalcin in ERK inhibitor + verapamil between the silicon concentrations; these varations are dose-dependent and indicate that ERK signaling is involved in the silicon-induced odontogenic differentiation of hDPCs.

Conclusions: The current study shows that silicon ions released from calcium silicate substrates play a key role in odontoblastic differentiation of hDPCs through calcium channels and modulate ERK activation.

Keywords: Calcium channel blocker; MAPK; calcium silicate cement; human dental pulp cells; odontogenic differentiation; verapamil.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase / analysis
  • Aluminum Compounds / pharmacology
  • Calcium Channel Blockers / pharmacology*
  • Calcium Channels / drug effects
  • Calcium Compounds / administration & dosage
  • Calcium Compounds / pharmacology*
  • Cell Culture Techniques
  • Cell Differentiation / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Dental Pulp / cytology*
  • Dental Pulp / drug effects
  • Dose-Response Relationship, Drug
  • Drug Combinations
  • Extracellular Matrix Proteins / analysis
  • Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
  • Extracellular Signal-Regulated MAP Kinases / drug effects
  • Flavonoids / pharmacology
  • Humans
  • MAP Kinase Signaling System / drug effects
  • Odontogenesis / drug effects*
  • Osteocalcin / analysis
  • Oxides / pharmacology
  • Phosphoproteins / analysis
  • Protein Kinase Inhibitors / pharmacology
  • Sialoglycoproteins / analysis
  • Silicate Cement / pharmacology
  • Silicates / administration & dosage
  • Silicates / pharmacology*
  • Silicon / administration & dosage
  • Silicon / pharmacology
  • Verapamil / antagonists & inhibitors
  • Verapamil / pharmacology*
  • p38 Mitogen-Activated Protein Kinases / drug effects

Substances

  • Aluminum Compounds
  • Calcium Channel Blockers
  • Calcium Channels
  • Calcium Compounds
  • DMP1 protein, human
  • Drug Combinations
  • Extracellular Matrix Proteins
  • Flavonoids
  • Oxides
  • Phosphoproteins
  • Protein Kinase Inhibitors
  • Sialoglycoproteins
  • Silicates
  • dentin sialophosphoprotein
  • mineral trioxide aggregate
  • Osteocalcin
  • Silicate Cement
  • Verapamil
  • Extracellular Signal-Regulated MAP Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Alkaline Phosphatase
  • calcium silicate
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
  • Silicon