Myostatin/ activin blocking combined with exercise reconditions skeletal muscle expression profile of mdx mice
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Myostatin/ activin blocking combined with exercise reconditions skeletal muscle expression profile of mdx mice. / Kainulainen, Heikki; Papaioannou, Konstantinos G.; Silvennoinen, Mika; Autio, Reija; Saarela, Janne; Oliveira, Bernardo M.; Nyqvist, Miro; Pasternack, Arja; Hoen, Peter A.C. ´t; Kujala, Urho M.; Ritvos, Olli; Hulmi, Juha J.
In: Molecular and Cellular Endocrinology, Vol. 399, 2015, p. 131-142.Research output: Contribution to journal › Article › Scientific › peer-review
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TY - JOUR
T1 - Myostatin/ activin blocking combined with exercise reconditions skeletal muscle expression profile of mdx mice
AU - Kainulainen, Heikki
AU - Papaioannou, Konstantinos G.
AU - Silvennoinen, Mika
AU - Autio, Reija
AU - Saarela, Janne
AU - Oliveira, Bernardo M.
AU - Nyqvist, Miro
AU - Pasternack, Arja
AU - Hoen, Peter A.C. ´t
AU - Kujala, Urho M.
AU - Ritvos, Olli
AU - Hulmi, Juha J.
N1 - Contribution: organisation=sgn,FACT1=1<br/>Portfolio EDEND: 2015-01-13<br/>Publisher name: Elsevier
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
U2 - 10.1016/j.mce.2014.10.001
DO - 10.1016/j.mce.2014.10.001
M3 - Article
VL - 399
SP - 131
EP - 142
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
SN - 0303-7207
ER -