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Role of satellite cells versus myofibers in muscle hypertrophy induced by inhibition of the myostatin/activin signaling pathway.
Proc Natl Acad Sci U S A. 2012 Aug 28; 109(35):E2353-60.PN

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+Show Affiliations

Department of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. sjlee@jhmi.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22869749

Citation

Lee, Se-Jin, et al. "Role of Satellite Cells Versus Myofibers in Muscle Hypertrophy Induced By Inhibition of the Myostatin/activin Signaling Pathway." Proceedings of the National Academy of Sciences of the United States of America, vol. 109, no. 35, 2012, pp. E2353-60.
Lee SJ, Huynh TV, Lee YS, et al. Role of satellite cells versus myofibers in muscle hypertrophy induced by inhibition of the myostatin/activin signaling pathway. Proc Natl Acad Sci USA. 2012;109(35):E2353-60.
Lee, S. J., Huynh, T. V., Lee, Y. S., Sebald, S. M., Wilcox-Adelman, S. A., Iwamori, N., Lepper, C., Matzuk, M. M., & Fan, C. M. (2012). Role of satellite cells versus myofibers in muscle hypertrophy induced by inhibition of the myostatin/activin signaling pathway. Proceedings of the National Academy of Sciences of the United States of America, 109(35), E2353-60. https://doi.org/10.1073/pnas.1206410109
Lee SJ, et al. Role of Satellite Cells Versus Myofibers in Muscle Hypertrophy Induced By Inhibition of the Myostatin/activin Signaling Pathway. Proc Natl Acad Sci USA. 2012 Aug 28;109(35):E2353-60. PubMed PMID: 22869749.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of satellite cells versus myofibers in muscle hypertrophy induced by inhibition of the myostatin/activin signaling pathway. AU - Lee,Se-Jin, AU - Huynh,Thanh V, AU - Lee,Yun-Sil, AU - Sebald,Suzanne M, AU - Wilcox-Adelman,Sarah A, AU - Iwamori,Naoki, AU - Lepper,Christoph, AU - Matzuk,Martin M, AU - Fan,Chen-Ming, Y1 - 2012/08/06/ PY - 2012/8/8/entrez PY - 2012/8/8/pubmed PY - 2012/12/12/medline SP - E2353 EP - 60 JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc. Natl. Acad. Sci. U.S.A. VL - 109 IS - 35 N2 - 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. SN - 1091-6490 UR - https://www.unboundmedicine.com/medline/citation/22869749/Role_of_satellite_cells_versus_myofibers_in_muscle_hypertrophy_induced_by_inhibition_of_the_myostatin/activin_signaling_pathway_ L2 - http://www.pnas.org/cgi/pmidlookup?view=long&pmid=22869749 DB - PRIME DP - Unbound Medicine ER -