Intramuscular adipogenesis is inhibited by myo-endothelial progenitors with functioning Bmpr1a signalling

Nat Commun. 2014 Jun 5;5:4063. doi: 10.1038/ncomms5063.

Abstract

Developing human muscle contains inter-myofibre progenitors expressing Bmp-receptor 1a (Bmpr1a) and Myf5 that respond to stimulation with Bmp4. Here we ablate Bmpr1a in Myf5- and MyoD-expressing cells in vivo. Mutant mice reveal increased intramuscular fat and reduced myofibre size in selected muscles, or following muscle injury. Myo-endothelial progenitors are the most affected cell type: clonal studies demonstrate that ablation of Bmpr1a in myo-endothelial cells results in decreased myogenic activity, while adipogenic differentiation is significantly increased. Downstream phospho-Smad 1, 5, 8 signalling is also severely decreased in mutant myo-endothelial cells. Lineage tracing of endothelial cells using VE-cadherin(Cre) driver failed to reveal a significant contribution of these cells to developing or injured skeletal muscle. Thus, myo-endothelial progenitors with functioning Bmpr1a signalling demonstrate myogenic potential, but their main function in vivo is to inhibit intramuscular adipogenesis, both through a cell-autonomous and a cell-cell interaction mechanism.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipogenesis / genetics*
  • Animals
  • Antigens, CD
  • Bone Morphogenetic Protein Receptors, Type I / genetics*
  • Cadherins
  • Endothelial Cells / metabolism
  • Mice
  • Mice, Knockout
  • Muscle, Skeletal / metabolism*
  • MyoD Protein / metabolism
  • Myogenic Regulatory Factor 5 / metabolism
  • Signal Transduction
  • Smad1 Protein / metabolism
  • Smad5 Protein / metabolism
  • Smad8 Protein / metabolism
  • Stem Cells / metabolism*

Substances

  • Antigens, CD
  • Cadherins
  • Myf5 protein, mouse
  • MyoD Protein
  • MyoD1 myogenic differentiation protein
  • Myogenic Regulatory Factor 5
  • Smad1 Protein
  • Smad1 protein, mouse
  • Smad5 Protein
  • Smad5 protein, mouse
  • Smad8 Protein
  • Smad9 protein, mouse
  • cadherin 5
  • Bmpr1a protein, mouse
  • Bone Morphogenetic Protein Receptors, Type I