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.
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).
To link to this article DOI: 10.1089/rej.2008.0815
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.
|Date Deposited:||18 Oct 2012 23:47|
|Last Modified:||24 Mar 2015 17:00|
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