TWIST1 promotes the odontoblast-like differentiation of dental stem cells

Adv Dent Res. 2011 Jul;23(3):280-4. doi: 10.1177/0022034511405387.

Abstract

Stem cells derived from the dental pulp of extracted human third molars (DPSCs) have the potential to differentiate into odontoblasts, osteoblasts, adipocytes, and neural cells when provided with the appropriate conditions. To advance the use of DPSCs for dentin regeneration, it is important to replicate the permissive signals that drive terminal events in odontoblast differentiation during tooth development. Such a strategy is likely to restore a dentin matrix that more resembles the tubular nature of primary dentin. Due to the limitations of culture conditions, the use of ex vivo gene therapy to drive the terminal differentiation of mineralizing cells holds considerable promise. In these studies, we asked whether the forced expression of TWIST1 in DPSCs could alter the potential of these cells to differentiate into odontoblast-like cells. Since the partnership between Runx2 and Twist1 proteins is known to control the onset of osteoblast terminal differentiation, we hypothesized that these genes act to control lineage determination of DPSCs. For the first time, our results showed that Twist1 overexpression in DPSCs enhanced the expression of DSPP, a gene that marks odontoblast terminal differentiation. Furthermore, co-transfection assays showed that Twist1 stimulates Dspp promoter activity by antagonizing Runx2 function in 293FT cells. Analysis of our in vitro data, taken together, suggests that lineage specification of DPSCs can be modulated through ex vivo gene modifications.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alkaline Phosphatase / analysis
  • Calcification, Physiologic / genetics
  • Cell Differentiation / genetics
  • Cell Line
  • Cell Lineage / genetics
  • Core Binding Factor Alpha 1 Subunit / antagonists & inhibitors
  • Core Binding Factor Alpha 1 Subunit / genetics
  • Dental Pulp / cytology*
  • Exons / genetics
  • Extracellular Matrix Proteins / analysis
  • Extracellular Matrix Proteins / genetics
  • Gene Expression Regulation / genetics
  • Gene Silencing
  • Genetic Vectors / genetics
  • Humans
  • Introns / genetics
  • Lentivirus / genetics
  • Nuclear Proteins / genetics*
  • Odontoblasts / physiology*
  • Osteoblasts / physiology
  • Osteocalcin / analysis
  • Osteopontin / analysis
  • Phosphoproteins / analysis
  • Phosphoproteins / genetics
  • Promoter Regions, Genetic / genetics
  • RNA, Small Interfering
  • Sialoglycoproteins / analysis
  • Sialoglycoproteins / genetics
  • Stem Cells / physiology*
  • Transfection / methods
  • Twist-Related Protein 1 / genetics*

Substances

  • Core Binding Factor Alpha 1 Subunit
  • DMP1 protein, human
  • Extracellular Matrix Proteins
  • Nuclear Proteins
  • Phosphoproteins
  • RNA, Small Interfering
  • RUNX2 protein, human
  • Sialoglycoproteins
  • TWIST1 protein, human
  • Twist-Related Protein 1
  • dentin sialophosphoprotein
  • Osteocalcin
  • Osteopontin
  • Alkaline Phosphatase