title: Myostatin regulates tissue potency and cardiac calcium-handling proteins.
abstract: 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.
authors: School of Molecular Biosciences (M.F.J., B.D.R.), Department of Animal Sciences (N.L., B.D.R.), Washington Center for Muscle Biology, Washington State University, Pullman, Washington 99164.
authors: Melissa F
authors: MF
authors: Jackson
authors: Naisi
authors: N
authors: Li
authors: Buel D
authors: BD
authors: Rodgers
mesh_terms: D050156:Adipogenesis; D000818:Animals; D020013:Calcium Signaling; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D003433:Crosses, Genetic; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D024510:Muscle Development; D050505:Mutant Proteins; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D055435:Myostatin / Q000235:genetics / Q000378:metabolism*; D010012:Osteogenesis; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012727:Sex Characteristics; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D002135:Calcium-Binding Proteins; D006657:Histones; C525912:Mstn protein, mouse; D050505:Mutant Proteins; D055435:Myostatin; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins