Myostatin/ activin blocking combined with exercise reconditions skeletal muscle expression profile of mdx mice

Heikki Kainulainen; Konstantinos G. Papaioannou; Mika Silvennoinen; Reija Autio; Janne Saarela; Bernardo M. Oliveira; Miro Nyqvist; Arja Pasternack; Peter A.C. ´t Hoen; Urho M. Kujala; Olli Ritvos; Juha J. Hulmi

doi:10.1016/j.mce.2014.10.001

Myostatin/ activin blocking combined with exercise reconditions skeletal muscle expression profile of mdx mice

Heikki Kainulainen, Konstantinos G. Papaioannou, Mika Silvennoinen, Reija Autio, Janne Saarela, Bernardo M. Oliveira, Miro Nyqvist, Arja Pasternack, Peter A.C. ´t Hoen, Urho M. Kujala, Olli Ritvos, Juha J. Hulmi

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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.

Translated title of the contribution	Myostatin/ activin blocking combined with exercise reconditions skeletal muscle expression profile of mdx mice
Original language	English
Pages (from-to)	131-142
Number of pages	12
Journal	Molecular and Cellular Endocrinology
Volume	399
DOIs	https://doi.org/10.1016/j.mce.2014.10.001
Publication status	Published - 2015
Publication type	A1 Journal article-refereed

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Kainulainen, H., Papaioannou, K. G., Silvennoinen, M., Autio, R., Saarela, J., Oliveira, B. M., Nyqvist, M., Pasternack, A., Hoen, P. A. C. ., Kujala, U. M., Ritvos, O., & Hulmi, J. J. (2015). Myostatin/ activin blocking combined with exercise reconditions skeletal muscle expression profile of mdx mice. Molecular and Cellular Endocrinology, 399, 131-142. https://doi.org/10.1016/j.mce.2014.10.001

@article{a2ad3884674e405e9384dcecf9a18327,

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.",

author = "Heikki Kainulainen and Papaioannou, {Konstantinos G.} and Mika Silvennoinen and Reija Autio and Janne Saarela and Oliveira, {Bernardo M.} and Miro Nyqvist and Arja Pasternack and Hoen, {Peter A.C. ´t} and Kujala, {Urho M.} and Olli Ritvos and Hulmi, {Juha J.}",

note = "Contribution: organisation=sgn,FACT1=1<br/>Portfolio EDEND: 2015-01-13<br/>Publisher name: Elsevier",

year = "2015",

doi = "10.1016/j.mce.2014.10.001",

language = "English",

volume = "399",

pages = "131--142",

journal = "Molecular and Cellular Endocrinology",

issn = "0303-7207",

publisher = "Elsevier",

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Kainulainen, H, Papaioannou, KG, Silvennoinen, M, Autio, R, Saarela, J, Oliveira, BM, Nyqvist, M, Pasternack, A, Hoen, PAC, Kujala, UM, Ritvos, O & Hulmi, JJ 2015, 'Myostatin/ activin blocking combined with exercise reconditions skeletal muscle expression profile of mdx mice', Molecular and Cellular Endocrinology, vol. 399, pp. 131-142. https://doi.org/10.1016/j.mce.2014.10.001

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

SN - 0303-7207

VL - 399

SP - 131

EP - 142

JO - Molecular and Cellular Endocrinology

JF - Molecular and Cellular Endocrinology

ER -

Myostatin/ activin blocking combined with exercise reconditions skeletal muscle expression profile of mdx mice

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