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Role of satellite cells versus myofibers in muscle hypertrophy induced by inhibition of the myostatin/activin signaling pathway.

Myostatin and activin A are structurally related secreted proteins that act to limit skeletal muscle growth. The cellular targets for myostatin and activin A in muscle and the role of satellite cells in mediating muscle hypertrophy induced by inhibition of this signaling pathway have not been fully elucidated. Here we show that myostatin/activin A inhibition can cause muscle hypertrophy in mice lacking either syndecan4 or Pax7, both of which are important for satellite cell function and development. Moreover, we show that muscle hypertrophy after pharmacological blockade of this pathway occurs without significant satellite cell proliferation and fusion to myofibers and without an increase in the number of myonuclei per myofiber. Finally, we show that genetic ablation of Acvr2b, which encodes a high-affinity receptor for myostatin and activin A specifically in myofibers is sufficient to induce muscle hypertrophy. All of these findings are consistent with satellite cells playing little or no role in myostatin/activin A signaling in vivo and render support that inhibition of this signaling pathway can be an effective therapeutic approach for increasing muscle growth even in disease settings characterized by satellite cell dysfunction.

Pubmed ID: 22869749

Authors

  • Lee SJ
  • Huynh TV
  • Lee YS
  • Sebald SM
  • Wilcox-Adelman SA
  • Iwamori N
  • Lepper C
  • Matzuk MM
  • Fan CM

Journal

Proceedings of the National Academy of Sciences of the United States of America

Publication Data

August 28, 2012

Associated Grants

  • Agency: NIH HHS, Id: DP5 OD009208
  • Agency: NIH HHS, Id: DP5OD009208
  • Agency: NINDS NIH HHS, Id: P01NS0720027
  • Agency: NIAMS NIH HHS, Id: R01 AR059685
  • Agency: NIAMS NIH HHS, Id: R01 AR060042
  • Agency: NIAMS NIH HHS, Id: R01 AR060636
  • Agency: NICHD NIH HHS, Id: R01 HD032067
  • Agency: NIAMS NIH HHS, Id: R01AR059685
  • Agency: NIAMS NIH HHS, Id: R01AR060042
  • Agency: NIAMS NIH HHS, Id: R01AR060636
  • Agency: NICHD NIH HHS, Id: R01HD032067

Mesh Terms

  • Activin Receptors, Type II
  • Activins
  • Animals
  • Follistatin
  • Hypertrophy
  • Membrane Fusion
  • Mice
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Muscle Fibers, Skeletal
  • Muscle, Skeletal
  • Myostatin
  • Organ Size
  • PAX7 Transcription Factor
  • Regeneration
  • Satellite Cells, Skeletal Muscle
  • Signal Transduction
  • Syndecan-4