title: Myostatin/activin blocking combined with exercise reconditions skeletal muscle expression profile of mdx mice.
abstract: Duchenne muscular dystrophy is characterized by muscle wasting and decreased aerobic metabolism. Exercise and blocking of myostatin/activin signaling may independently or combined counteract muscle wasting and dystrophies. The effects of myostatin/activin blocking using soluble activin receptor-Fc (sActRIIB-Fc) administration and wheel running were tested alone or in combination for 7 weeks in dystrophic mdx mice. Expression microarray analysis revealed decreased aerobic metabolism in the gastrocnemius muscle of mdx mice compared to healthy mice. This was not due to reduced home-cage physical activity, and was further downregulated upon sActRIIB-Fc treatment in enlarged muscles. However, exercise activated pathways of aerobic metabolism and counteracted the negative effects of sActRIIB-Fc. Exercise and sActRIIB-Fc synergistically increased expression of major urinary protein, but exercise blocked sActRIIB-Fc induced phosphorylation of STAT5 in gastrocnemius muscle. In conclusion, exercise alone or in combination with myostatin/activin blocking corrects aerobic gene expression profiles of dystrophic muscle toward healthy wild type mice profiles.
authors.affiliation: Department of Biology of Physical Activity, Neuromuscular Research Center, University of Jyväskylä, Rautpohjankatu 8, P.O. Box 35, Jyväskylä FI-40014, Finland.
authors.forename: Heikki
authors.initials: H
authors.lastname: Kainulainen
authors.affiliation: Department of Biology of Physical Activity, Neuromuscular Research Center, University of Jyväskylä, Rautpohjankatu 8, P.O. Box 35, Jyväskylä FI-40014, Finland.
authors.forename: Konstantinos G
authors.initials: KG
authors.lastname: Papaioannou
authors.affiliation: Department of Biology of Physical Activity, Neuromuscular Research Center, University of Jyväskylä, Rautpohjankatu 8, P.O. Box 35, Jyväskylä FI-40014, Finland.
authors.forename: Mika
authors.initials: M
authors.lastname: Silvennoinen
authors.affiliation: Department of Signal Processing, Tampere University of Technology, Korkeakoulunkatu 1, P.O. BOX 553, Tampere FI-33101, Finland.
authors.forename: Reija
authors.initials: R
authors.lastname: Autio
authors.affiliation: Department of Biology of Physical Activity, Neuromuscular Research Center, University of Jyväskylä, Rautpohjankatu 8, P.O. Box 35, Jyväskylä FI-40014, Finland.
authors.forename: Janne
authors.initials: J
authors.lastname: Saarela
authors.affiliation: Department of Biology of Physical Activity, Neuromuscular Research Center, University of Jyväskylä, Rautpohjankatu 8, P.O. Box 35, Jyväskylä FI-40014, Finland.
authors.forename: Bernardo M
authors.initials: BM
authors.lastname: Oliveira
authors.affiliation: Department of Medical Biochemistry and Genetics, University of Turku, Kiinamyllynkatu 10, Turku FIN-20520, Finland.
authors.forename: Miro
authors.initials: M
authors.lastname: Nyqvist
authors.affiliation: Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Haartmaninkatu 3, P.O. Box 21, Helsinki FIN-00014, Finland.
authors.forename: Arja
authors.initials: A
authors.lastname: Pasternack
authors.affiliation: Department of Human Genetics, Leiden University Medical Center (LUMC), Postzone S-04-P, PO Box 9600, Leiden 2300 RC, The Netherlands.
authors.forename: Peter A C
authors.initials: PA
authors.lastname: 't Hoen
authors.affiliation: Department of Health Sciences, University of Jyväskylä, Rautpohjankatu 8, P.O. Box 35, Jyväskylä FI-40014, Finland.
authors.forename: Urho M
authors.initials: UM
authors.lastname: Kujala
authors.affiliation: Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Haartmaninkatu 3, P.O. Box 21, Helsinki FIN-00014, Finland.
authors.forename: Olli
authors.initials: O
authors.lastname: Ritvos
authors.affiliation: Department of Biology of Physical Activity, Neuromuscular Research Center, University of Jyväskylä, Rautpohjankatu 8, P.O. Box 35, Jyväskylä FI-40014, Finland. Electronic address: juha.hulmi@jyu.fi.
authors.forename: Juha J
authors.initials: JJ
authors.lastname: Hulmi
mesh_terms: D030301:Activin Receptors, Type II / Q000235:genetics / Q000494:pharmacology*; D000818:Animals; D028322:Inhibin-beta Subunits / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051379:Mice; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000378:metabolism*; D055435:Myostatin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010805:Physical Conditioning, Animal; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000494:pharmacology; D050799:STAT5 Transcription Factor / Q000378:metabolism
chemical_list: C525912:Mstn protein, mouse; D055435:Myostatin; D011993:Recombinant Fusion Proteins; D050799:STAT5 Transcription Factor; C103008:inhibin beta A subunit; D028322:Inhibin-beta Subunits; D030301:Activin Receptors, Type II; C425584:activin receptor type II-B
keywords: Muscle hypertrophy; Muscular dystrophy; Oxidative metabolism; Physical activity; mRNA profiling