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

Se Jin Lee, Thanh V. Huynh, Yun Sil Lee, Suzanne M. Sebald, Sarah A. Wilcox-Adelman, Naoki Iwamori, Christoph Lepper, Martin M. Matzuk, Chen Ming Fan

Research output: Contribution to journalArticle

101 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)E2353-E2360
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number35
DOIs
Publication statusPublished - Aug 28 2012
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General

Fingerprint Dive into the research topics of 'Role of satellite cells versus myofibers in muscle hypertrophy induced by inhibition of the myostatin/activin signaling pathway'. Together they form a unique fingerprint.

  • Cite this