Force and scleraxis synergistically promote the commitment of human ES cells derived MSCs to tenocytes

Sci Rep. 2012;2:977. doi: 10.1038/srep00977. Epub 2012 Dec 14.

Abstract

As tendon stem/progenitor cells were reported to be rare in tendon tissues, tendons as vulnerable targets of sports injury possess poor self-repair capability. Human ESCs (hESCs) represent a promising approach to tendon regeneration. But their teno-lineage differentiation strategy has yet to be defined. Here, we report that force combined with the tendon-specific transcription factor scleraxis synergistically promoted commitment of hESCs to tenocyte for functional tissue regeneration. Force and scleraxis can independently induce tendon differentiation. However, force alone concomitantly activated osteogenesis, while scleraxis alone was not sufficient to commit, but augment tendon differentiation. Scleraxis synergistically augmented the efficacy of force on teno-lineage differentiation and inhibited the osteo-lineage differentiation by antagonized BMP signaling cascade. The findings not only demonstrated a novel strategy of directing hESC differentiation to tenocyte for functional tendon regeneration, but also offered insights into understanding the network of force, scleraxis and bmp2 controlling tendon-lineage differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Bone Morphogenetic Proteins / antagonists & inhibitors
  • Bone Morphogenetic Proteins / metabolism
  • Cell Differentiation
  • Cell Line
  • Cell Lineage
  • Collagen / metabolism
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / metabolism
  • Humans
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Mice, Nude
  • Osteogenesis
  • Regeneration
  • Signal Transduction
  • Stress, Mechanical*
  • Tendons / cytology*
  • Tendons / metabolism
  • Tissue Engineering
  • Transfection

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Bone Morphogenetic Proteins
  • SCX protein, human
  • Collagen