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Adeno-associated virus-8-Mediated intravenous transfer of myostatin propeptide leads to systemic functional improvements of slow but not fast muscle

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Foster, K., Graham, I. R., Otto, A., Foster, H., Trollet, C., Yaworsky, P. J., Walsh, F. S., Bickham, D., Curtin, N. A., Kawar, S. L., Patel, K. and Dickson, G. (2009) Adeno-associated virus-8-Mediated intravenous transfer of myostatin propeptide leads to systemic functional improvements of slow but not fast muscle. Rejuvenation Research, 12 (2). pp. 85-93. ISSN 1549-1684

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To link to this article DOI: 10.1089/rej.2008.0815

Abstract/Summary

Myostatin is a member of the transformating growth factor-_ (TGF-_) superfamily of proteins and is produced almost exclusively in skeletal muscle tissue, where it is secreted and circulates as a serum protein. Myostatin acts as a negative regulator of muscle mass through the canonical SMAD2/3/4 signaling pathway. Naturally occurring myostatin mutants exhibit a ‘double muscling’ phenotype in which muscle mass is dramatically increased as a result of both hypertrophy and hyperplasia. Myostatin is naturally inhibited by its own propeptide; therefore, we assessed the impact of adeno associated virus-8 (AAV8) myostatin propeptide vectors when systemically introduced in MF-1 mice. We noted a significant systemic increase in muscle mass in both slow and fast muscle phenotypes, with no evidence of hyperplasia; however, the nuclei-to- cytoplasm ratio in all myofiber types was significantly reduced. An increase in muscle mass in slow (soleus) muscle led to an increase in force output; however, an increase in fast (extensor digitorum longus [EDL]) muscle mass did not increase force output. These results suggest that the use of gene therapeutic regimens of myostatin inhibition for age-related or disease-related muscle loss may have muscle-specific effects.

Item Type:Article
Refereed:Yes
Divisions:Interdisciplinary centres and themes > Institute for Cardiovascular and Metabolic Research (ICMR)
Faculty of Life Sciences > School of Biological Sciences > Biomedical Sciences
ID Code:29504
Uncontrolled Keywords:VIRUS SEROTYPE-8 VECTORS, SKELETAL-MUSCLE, MYOBLAST PROLIFERATION, NEGATIVE REGULATOR, DYSTROPHIC MUSCLE, SELF-RENEWAL, STEM-CELL, GROWTH, MICE, Gene Expression
Publisher:Mary Ann Liebert Inc.

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