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Alterations in gene expression precede sarcopenia and osteopenia in botulinum toxin immobilized mice
J B Vegger1, A Brüel, A F Dahlgaard
1Department of Biomedicine, Aarhus University, Wilhelm Meyers Allé 3, DK-8000 Aarhus C, Denmark.
Objectives:
To investigate alteration of bone and muscle gene expression at different time points during 3 weeks of botulinum toxin (BTX) induced immobilization and how this correlate with conventional analysis of bone and muscle.
Methods:
Thirty-five 16-week-old female C57BL/6-mice were investigated; 15 were injected with BTX, 15 served as age-matched controls, and 5 as baseline. 5 BTX-injected and 5 control mice were euthanized after 1, 2, and 3 weeks. Analysis included RT-qPCR, dynamic bone histomorphometry, DEXA, µCT, mechanical testing, and muscle cell cross-sectional-area (CSA).
Results:
Genes related to osteoblasts were expressed at a lower level after 1 week, but not after 2 and 3 weeks of disuse. Moreover, genes related to osteoclasts were expressed at a higher level after 1 and 2 weeks of disuse, whereafter they approached the level of the controls. Genes related to muscle atrophy were upregulated 1 and 2 weeks after the BTX-injection, but not after 3 weeks. In contrast, deterioration of bone microstructure and strength, and reduction in muscle cell CSA were most evident after 3 weeks of disuse.
Conclusions:
Gene expression should be investigated during the first two weeks of immobilization, whereas changes in bone microstructure and muscle cell CSA are most prominent after 3 weeks of immobilization.
