Résumé :
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Previously, we have shown that null mutation of myostatin resulted in muscle fibre hypertrophy that is independent of satellite cell activity. Here, we investigated the effect of myostatin blockade in mature mouse muscle. Myostatin was blocked after intramuscular injection of recombinant AAV-2/1 coding for the myostatin propeptide (AAV-prop) into tibialis anterior (TA) muscle of 6 weeks old female C57Bl6 mice. The local overexpression of myostatin propeptide resulted in a 28% increase of muscle weight after 28 days of treatment compared to the contralateral side that was injected with a AAV-Mseap control vector (P<0.001). Morphometric analysis revealed a 16% increase of mean single fibre area following AAV-prop injection compared to the controls (P=0.004). The mean fibre number after AAV-prop vector injection was 3328 compared to 3420 after control vector injection (P=0.47). Thus, excessive growth after myostatin blockade resulted exclusively from fibre hypertrophy. Next, the number of myonuclei was determined on cross sections of TA muscles. Muscle fibres contained on average 0.65 myonuclei after injection of AAV-prop compared to 0.63 myonuclei after control vector injection (P=0.77). We finally determined the effect of myostatin blockade on satellite cell number. We injected AAV-prop vector into TA muscle of Myf5nlacZ/+ mice, in which satellite cells express the transgene lacZ. One month after injection of AAV-prop, muscle fibres contained on average 32 satellite cells versus 25 satellite cells per 1000 fibres after control vector injection, a difference that was statistically not significant (P=0.31). As Myf-5 is expressed in quiescent as well as in activated proliferating satellite cells, we can conclude that satellite cell activity is not increased after myostatin blockade. Above results confirm findings from previous analysis of constitutive myostatin knockout mice. Myostatin blockade in adult muscle resulted in fibre hypertrophy without concomitant increase in myonuclear number and without any evidence of increased satellite cell activity.
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