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BMC Musculoskeletal Disorders
Published in: BMC Musculoskeletal Disorders 1/2017

Open Access 01-12-2017 | Research article

Treatment with soluble activin type IIB-receptor improves bone mass and strength in a mouse model of Duchenne muscular dystrophy

Authors: Tero Puolakkainen, Hongqian Ma, Heikki Kainulainen, Arja Pasternack, Timo Rantalainen, Olli Ritvos, Kristiina Heikinheimo, Juha J. Hulmi, Riku Kiviranta

Published in: BMC Musculoskeletal Disorders | Issue 1/2017

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Abstract

Background

Inhibition of activin/myostatin pathway has emerged as a novel approach to increase muscle mass and bone strength. Duchenne muscular dystrophy (DMD) is a neuromuscular disorder that leads to progressive muscle degeneration and also high incidence of fractures. The aim of our study was to test whether inhibition of activin receptor IIB ligands with or without exercise could improve bone strength in the mdx mouse model for DMD.

Methods

Thirty-two mdx mice were divided to running and non-running groups and to receive either PBS control or soluble activin type IIB-receptor (ActRIIB-Fc) once weekly for 7 weeks.

Results

Treatment of mdx mice with ActRIIB-Fc resulted in significantly increased body and muscle weights in both sedentary and exercising mice. Femoral μCT analysis showed increased bone volume and trabecular number (BV/TV +80%, Tb.N +70%, P < 0.05) in both ActRIIB-Fc treated groups. Running also resulted in increased bone volume and trabecular number in PBS-treated mice. However, there was no significant difference in trabecular bone structure or volumetric bone mineral density between the ActRIIB-Fc and ActRIIB-Fc-R indicating that running did not further improve bone structure in ActRIIB-Fc-treated mice. ActRIIB-Fc increased bone mass also in vertebrae (BV/TV +20%, Tb.N +30%, P < 0.05) but the effects were more modest. The number of osteoclasts was decreased in histological analysis and the expression of several osteoblast marker genes was increased in ActRIIB-Fc treated mice suggesting decreased bone resorption and increased bone formation in these mice. Increased bone mass in femurs translated into enhanced bone strength in biomechanical testing as the maximum force and stiffness were significantly elevated in ActRIIB-Fc-treated mice.

Conclusions

Our results indicate that treatment of mdx mice with the soluble ActRIIB-Fc results in a robust increase in bone mass, without any additive effect by voluntary running. Thus ActRIIB-Fc could be an attractive option in the treatment of musculoskeletal disorders.
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Metadata
Title
Treatment with soluble activin type IIB-receptor improves bone mass and strength in a mouse model of Duchenne muscular dystrophy
Authors
Tero Puolakkainen
Hongqian Ma
Heikki Kainulainen
Arja Pasternack
Timo Rantalainen
Olli Ritvos
Kristiina Heikinheimo
Juha J. Hulmi
Riku Kiviranta
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Musculoskeletal Disorders / Issue 1/2017
Electronic ISSN: 1471-2474
DOI
https://doi.org/10.1186/s12891-016-1366-3

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