Modulation of myostatin expression during modified muscle use

Abstract

Previous findings have provided strong evidence that myostatin functions as a negative regulator of muscle mass during development and growth. In the present study, we test the hypothesis that myostatin may serve a similar function in fully differentiated muscle experiencing modified loading. Our findings show that myostatin expression can be modulated in fully differentiated, nonpathological skeletal muscle in a manner that is inversely related to changes in muscle mass. Atrophy of rat hind limb muscles induced by 10 days of unloading resulted in a 16% decrease in plantaris mass, a 110% increase in myostatin mRNA, and a 37% increase in myostatin protein. Immunohistochemical observations showed a detectable increase in myostatin concentration at myotendinous junctions during muscle unloading. The concentration of myostatin mRNA and protein returned to values not significantly different from ambulatory controls after 4 days of reloading, during which time plantaris mass also returned to control values. However, the results also show that periods of 30 min of daily muscle loading during the unloading period were sufficient to prevent significant losses of muscle mass caused by unloading, although myostatin mRNA still showed a 55% increase in concentration. Thus, significant increases in myostatin expression are not sufficient for muscle mass loss, although muscle mass loss during unloading is accompanied by increases in myostatin.

Effect of RNA oligonucleotide targeting Foxo-1 on muscle growth in normal and cancer cachexia mice

“…[9][10][11] Increases in GDF-8 expression have been observed in conditions of muscle atrophy and/or dystrophy, while the GDF-8 mRNA is modified in response to muscle loading after atrophy. 12 To explore Foxo-1 as a potential molecular target for muscle wasting conditions and gain insight of the mechanism of Foxo-1 regulation of muscle development and growth, we used a modified RNA oligonucleotide targeting the Foxo-1 mRNA in muscle cells and in normal and cachectic mice. Our studies demonstrated that the modified RNA oligonucleotide could decrease the expression of Foxo-1 in cells and in vivo, leading to an increase in muscle weight.…”

Preparation and application of rat myostatin antiserum

“…It has been suggested that MSTN could inhibit myogenesis and promote atrophy of adult skeletal muscle by suppressing proliferation of satellite cells [17] . However, other studies supported that the role of MSTN was to inhibit hypertrophy of skeletal muscle rather than to induce atrophy [11,18,19] . Our previous studies showed that there was an apparent association between MSTN expression and rat sciatic nerve injury [12,13] .…”

“…It has been reported that 10 days of hindlimb unloading causes a 16% atrophy in rat plantaris muscle with a 110% and 37% increase in MSTN mRNA and protein level, respectively. However, 30 min daily muscle loading during the unloading period helps prevent significant loss of muscle mass, despite a concomitant 55% increase in myostatin mRNA expression [11] . We have previously described expression pattern profile of rat MSTN in response to muscle atrophy induced by sciatic nerve injury [12,13] .…”

Muscle type-specific responses of myoD and calpain 3 expression to recombinant porcine growth hormone in the pig

“…Myostatin knockout mice deposit two-to three-fold greater muscle mass than their wild-type littermates due to increase in both muscle fibre number (hyperplasia) and the fibre cross-sectional area (hypotrophy) (McPherron et al, 1997) during embryonic and early postnatal development (Wehling et al, 2000;Whittemore et al, 2003). A disruption of myostatin function by transgenic expression of its propetide (the 5 0 region, 866 nucleotides) was reported to result in significant muscle growth (Yang et al, 2001).…”