Activin is a known physiologic regulator of bone metabolism. Ovariectomy-induced osteopenia has been shown to be attenuated by injection of the activin type IIA decoy receptor (ActRIIA-Fc). However, immobilization-induced osteopenia is driven by different pathways than ovariectomy-induced osteopenia, and the role of activin in immobilization-induced osteopenia has not yet been elucidated.
The purpose of the study was to investigate the possible attenuation of the muscle and bone deterioration following botulinum toxin A (BTX) induced immobilization in mice.
Sixteen-week-old C57BL/6 mice were divided into five groups: baseline (n=10), control (n=12), ActRIIA-Fc (n=12), BTX (n=12), and BTX+ActRIIA-Fc (n=12). Immobilization was induced by injecting 2 IU/100 g BTX in the right hind limb musculature. The mice were euthanized after 21 days. Rectus femoris muscle mass and BMD of the whole femur were determined and μCT analyses of the mid-diaphyseal femur were performed. All experimental procedures were approved by the Danish Animal Experiments Inspectorate.
The ActRIIA-Fc treatment resulted in greater muscle weight (+8%, P<0.05) in the left (non-injected) limb compared with the control group. In the right limb (BTX-injected) of the BTX+ActRIIA-Fc group, treatment resulted in a greater muscle weight (+11%, borderline significant, P=0.05) than in the BTX group. ActRIIA-Fc mice had an 8% (P<0.05) higher femoral BMD than control mice and BTX+ActRIIA-Fc mice had a 14% (P<0.05) higher femoral BMD than BTX mice. At the mid-diaphyseal femur ActRIIA-Fc mice had significantly (+9%, P<0.05) higher bone area with no difference observed in tissue area or marrow area compared with control mice. BTX+ActRIIA-Fc mice had a significantly greater tissue area (+5%, P<0.05) and bone area (+13%, P<0.05) than BTX mice.
Conclusion: In conclusion The immobilization-induced loss of muscle mass, bone density, and bone area may be ameliorated by treatment with ActRIIA-Fc.
17 May 2014 - 20 May 2014