Treatment with soluble activin type IIB-receptor improves bone mass and strength in a mouse model of Duchenne muscular dystrophy
Puolakkainen, T., Ma, H., Kainulainen, H., Pasternack, A., Rantalainen, T., Ritvos, O., Heikinheimo, K., Hulmi, J., & Kiviranta, R. (2017). Treatment with soluble activin type IIB-receptor improves bone mass and strength in a mouse model of Duchenne muscular dystrophy. BMC Musculoskeletal Disorders, 18(1), Article 20. https://doi.org/10.1186/s12891-016-1366-3
Julkaistu sarjassa
BMC Musculoskeletal DisordersTekijät
Päivämäärä
2017Tekijänoikeudet
© The Author(s), 2017. This is an open access article under the terms of the Creative Commons Attribution 4.0 International License.
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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BioMed CentralISSN Hae Julkaisufoorumista
1471-2474Julkaisu tutkimustietojärjestelmässä
https://converis.jyu.fi/converis/portal/detail/Publication/26491770
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