Molecular, cellular and physiological investigation of myostatin propeptide-mediated muscle growth in adult mice

Matsakas, A., Foster, K., Otto, A., Macharia, R., Elashry, M. I., Feist, S., Graham, I., Foster, H., Yaworsky, P., Walsh, F., Dickson, G. and Patel, K. (2009) Molecular, cellular and physiological investigation of myostatin propeptide-mediated muscle growth in adult mice. Neuromuscular Disorders, 19 (7). pp. 489-499. ISSN 0960-8966 doi: 10.1016/j.nmd.2009.06.367

Abstract/Summary

Inhibition of myostatin signalling or its biological activity has recently emerged as a potential remedial approach against muscle wasting and degenerative diseases such as muscular dystrophies. In the present study we systemically administered a recombinant AAV8 vector expressing a mutated myostatin propeptide (AAV8ProMyo) to healthy mice in order to assess its impact on the histological, cellular and physiological properties of the skeletal muscle, exploiting the fact that myostatin is naturally inhibited by its own propeptide. We report that a single intravenous administration of AAV8ProMyo leads to increases in muscle mass of tibialis anterior, extensor digitorum longus and gastrocnemius muscles 8 weeks post-injection and tibialis anterior, gastrocnemius and rectus femoris muscles 17 weeks post-injection. Moreover, treatment resulted in muscle fibre hypertrophy but not hyperplasia, with IIB myofibres responding to the greatest extent following propeptide-induced myostatin inhibition. Additionally, myofibre nuclear: cytoplasmic ratio was decreased in the AAV8ProMyo treated animals. Importantly, the hypertrophic EDL muscle 8 weeks after AAV8ProMyo treatment did not show the dramatic decrease in specific force displayed by the germline myostatin null mice. (C) 2009 Elsevier B.V. All rights reserved.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/9648
Item Type	Article
Refereed	Yes
Divisions	Life Sciences > School of Biological Sciences Interdisciplinary centres and themes > Institute for Cardiovascular and Metabolic Research (ICMR)
Uncontrolled Keywords	Myostatin, Satellite cell, Physiology, Skeletal, Muscle, Hypertrophy, Therapy, Propeptide, SKELETAL-MUSCLE, MYOBLAST PROLIFERATION, CONTRACTILE PROPERTIES, MUSCULAR-DYSTROPHY, TRANSGENIC MICE, DEFICIENT MICE, STEM-CELL, MDX, MICE, GENE, MASS
Download/View statistics	View download statistics for this item