Résumé :
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A powerful inhibition of muscle growth is exerted by myostatin, a member of the TGF-ß family of signalling molecules. Loss of myostatin after gene knockout results in the excessive growth of skeletal muscle. Despite a larger muscle mass of myostatin KO mice relative to age matched controls, there was a severe decrease in maximum tetanic force generation of the EDL in sedentary myostatin knockout mice. Consequently, force generation expressed as a function of muscle weight was strongly decreased relative to controls. Interestingly, such force decline in myostatin KO mice could be reversed upon a swimming exercise protocol. Myostatin nulls could improve their exercise capacity, however, the time to exhaustion remained far lower compared to wild-types, indicating a large deficiency in forced exercise capacity. After the end of the long term exercise protocol, myostatin deficient muscle improved the maximal tetanic force to wild-type values, however, specific force remained compromised. Excessive muscle growth in absence of myostatin predominantly resulted from muscle fibre hypertrophy. This hypertrophy was not dependent on satellite cell activity. In two mouse models with myostatin-null mutation, constitutive (mstn-/-) and compact (BEHc/c), myofibres contained fewer myonuclei and fewer satellite cells despite an increase of up to 93% in muscle mass. Similarly, myofibre hypertrophy resulting from postnatal over-expression of myostatin propeptide involved no detectable satellite cell hyperactivity. No effect of myostatin on satellite cell proliferation could be observed in vitro, while activin receptors of myostatin signalling became down-regulated in postnatal satellite cells. Importantly, in dystrophic (mdx) mice, lack of myostatin (mstn-/-mdx) did not result in enhanced muscle regeneration. In conclusion, sustained muscle hypertrophy elicited by the blockade or absence of myostatin was independent of satellite cell activity. Such hypertrophic muscle was functionally compromised in sedendary mice and improved partially upon exercise. The reason for the depressed specific force remains unknown.
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