TWIST family of basic helix-loop-helix transcription factors mediate human mesenchymal stem cell growth and commitment

Stem Cells. 2009 Oct;27(10):2457-68. doi: 10.1002/stem.181.

Abstract

The TWIST family of basic helix-loop-helix transcription factors, Twist-1 and Dermo-1 are known mediators of mesodermal tissue development and contribute to correct patterning of the skeleton. In this study, we demonstrate that freshly purified human bone marrow-derived mesenchymal stromal/stem cells (MSC) express high levels of Twist-1 and Dermo-1 which are downregulated following ex vivo expansion. Enforced expression of Twist-1 or Dermo-1 in human MSC cultures increased expression of the MSC marker, STRO-1, and the early osteogenic transcription factors, Runx2 and Msx2. Conversely, overexpression of Twist-1 and Dermo-1 was associated with a decrease in the gene expression of osteoblast-associated markers, bone morphogenic protein-2, bone sialoprotein, osteopontin, alkaline phosphatase and osteocalcin. High expressing Twist-1 or Dermo-1 MSC lines exhibited an enhanced proliferative potential of approximately 2.5-fold compared with control MSC populations that were associated with elevated levels of Id-1 and Id-2 gene expression. Functional studies demonstrated that high expressing Twist-1 and Dermo-1 MSC displayed a decreased capacity for osteo/chondrogenic differentiation and an enhanced capacity to undergo adipogenesis. These findings implicate the TWIST gene family members as potential mediators of MSC self-renewal and lineage commitment in postnatal skeletal tissues by exerting their effects on genes involved in the early stages of bone development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipogenesis / physiology
  • Adult
  • Biomarkers / analysis
  • Biomarkers / metabolism
  • Bone Development / physiology*
  • Cell Differentiation / physiology*
  • Cell Lineage / physiology*
  • Cell Proliferation*
  • Cells, Cultured
  • Down-Regulation / physiology
  • Humans
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Osteoblasts / metabolism
  • Osteogenesis / physiology
  • Proteins / analysis
  • Proteins / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Transcription Factors / analysis
  • Transcription Factors / metabolism
  • Twist-Related Protein 1 / genetics
  • Twist-Related Protein 1 / metabolism*
  • Young Adult

Substances

  • Biomarkers
  • Nuclear Proteins
  • Proteins
  • Repressor Proteins
  • TWIST1 protein, human
  • TWIST2 protein, human
  • Transcription Factors
  • Twist-Related Protein 1
  • Twist2 protein, mouse