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

Puolakkainen, Tero, Ma, Hongqian, Kainulainen, Heikki, Pasternack, Arja, Rantalainen, Timo, Ritvos, Olli, Heikinheimo, Kristiina, Hulmi, Juha J. and Kiviranta, Riku 2017, Treatment with soluble activin type IIB-receptor improves bone mass and strength in a mouse model of Duchenne muscular dystrophy, BMC musculoskeletal disorders, vol. 18, pp. 1-11, doi: 10.1186/s12891-016-1366-3.

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Title Treatment with soluble activin type IIB-receptor improves bone mass and strength in a mouse model of Duchenne muscular dystrophy
Author(s) Puolakkainen, Tero
Ma, Hongqian
Kainulainen, Heikki
Pasternack, Arja
Rantalainen, TimoORCID iD for Rantalainen, Timo orcid.org/0000-0001-6977-4782
Ritvos, Olli
Heikinheimo, Kristiina
Hulmi, Juha J.
Kiviranta, Riku
Journal name BMC musculoskeletal disorders
Volume number 18
Article ID 20
Start page 1
End page 11
Total pages 11
Publisher BioMed Central
Place of publication London, Eng.
Publication date 2017-01-19
ISSN 1471-2474
Keyword(s) Animal models
Bone μCT
Bone-muscle interactions
Exercise
TGF-βs
Summary 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.
Language eng
DOI 10.1186/s12891-016-1366-3
Field of Research 110399 Clinical Sciences not elsewhere classified
1103 Clinical Sciences
Socio Economic Objective 920116 Skeletal System and Disorders (incl. Arthritis)
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2017, The Authors
Free to Read? Yes
Use Rights Creative Commons Attribution licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30093595

Document type: Journal Article
Collections: School of Exercise and Nutrition Sciences
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.