title: Role of satellite cells versus myofibers in muscle hypertrophy induced by inhibition of the myostatin/activin signaling pathway.
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.
authors.affiliation: Department of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. sjlee@jhmi.edu
authors.forename: Se-Jin
authors.initials: SJ
authors.lastname: Lee
authors.forename: Thanh V
authors.initials: TV
authors.lastname: Huynh
authors.forename: Yun-Sil
authors.initials: YS
authors.lastname: Lee
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Sebald
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Wilcox-Adelman
authors.forename: Naoki
authors.initials: N
authors.lastname: Iwamori
authors.forename: Christoph
authors.initials: C
authors.lastname: Lepper
authors.forename: Martin M
authors.initials: MM
authors.lastname: Matzuk
authors.forename: Chen-Ming
authors.initials: CM
authors.lastname: Fan
mesh_terms: D030301:Activin Receptors, Type II / Q000235:genetics / Q000378:metabolism; D028341:Activins / Q000378:metabolism*; D000818:Animals; D038681:Follistatin / Q000235:genetics / Q000378:metabolism; D006984:Hypertrophy; D008561:Membrane Fusion / Q000502:physiology; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018485:Muscle Fibers, Skeletal / Q000166:cytology* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology; D055435:Myostatin / Q000378:metabolism*; D009929:Organ Size; D051763:PAX7 Transcription Factor / Q000235:genetics / Q000378:metabolism; D012038:Regeneration / Q000502:physiology; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D053671:Syndecan-4 / Q000235:genetics / Q000378:metabolism
chemical_list: D038681:Follistatin; C525912:Mstn protein, mouse; D055435:Myostatin; D051763:PAX7 Transcription Factor; C497322:Pax7 protein, mouse; C508306:Sdc4 protein, mouse; D053671:Syndecan-4; C422405:activin A; D028341:Activins; D030301:Activin Receptors, Type II; C425584:activin receptor type II-B