Myostatin Regulates Tissue Potency and Cardiac Calcium-Handling Proteins

Attenuating myostatin enhances striated muscle growth, reduces adiposity, and improves cardiac contractility. To determine whether myostatin influences tissue potency in a manner that could control such pleiotropic actions, we generated label-retaining mice with wild-type and mstn−/− (Jekyll) backgr...

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Bibliographic Details
Published in:Endocrinology (Philadelphia) 2014-05, Vol.155 (5), p.1771-1785
Main Authors: Jackson, Melissa F, Li, Naisi, Rodgers, Buel D
Format: Article
Language:English
Subjects:
Adipogenesis
Animals
Calcium Signaling
Calcium-Binding Proteins - metabolism
Crosses, Genetic
Female
Green Fluorescent Proteins - genetics
Green Fluorescent Proteins - metabolism
Growth Factors-Cytokines
Histones - genetics
Histones - metabolism
Male
Mice
Mice, Knockout
Mice, Transgenic
Muscle Development
Mutant Proteins
Myocardium - cytology
Myocardium - metabolism
Myostatin - genetics
Myostatin - metabolism
Osteogenesis
Recombinant Fusion Proteins - metabolism
Sex Characteristics
Stem Cells - cytology
Stem Cells - metabolism
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Summary:Attenuating myostatin enhances striated muscle growth, reduces adiposity, and improves cardiac contractility. To determine whether myostatin influences tissue potency in a manner that could control such pleiotropic actions, we generated label-retaining mice with wild-type and mstn−/− (Jekyll) backgrounds in which slow-cycling stem, transit-amplifying, and progenitor cells are preferentially labeled by histone 2B/green fluorescent protein. Jekyll mice were born with fewer label-retaining cells (LRCs) in muscle and heart, consistent with increased stem/progenitor cell contributions to embryonic growth of both tissues. Cardiac LRC recruitment from noncardiac sources occurred in both groups, but lasted longer in Jekyll hearts, whereas heightened β-adrenergic sensitivity of mstn−/− hearts was explained by elevated SERCA2a, phospholamban, and β2-adrenergic receptor levels. Jekyll mice were also born with more adipose LRCs despite significantly smaller tissue weights. Reduced adiposity in mstn−/− animals is therefore due to reduced lipid deposition as adipoprogenitor pools appear to be enhanced. By contrast, increased bone densities of mstn−/− mice are likely compensatory to hypermuscularity because LRC counts were similar in Jekyll and wild-type tibia. Myostatin therefore significantly influences the potency of different tissues, not just muscle, as well as cardiac Ca2+-handling proteins. Thus, the pleiotropic phenotype of mstn−/− animals may not be due to enhanced muscle development per se, but also to altered stem/progenitor cell pools that ultimately influence tissue potency.
ISSN:0013-7227
1945-7170
DOI:10.1210/en.2013-2014