title: Alterations in gene expression precede sarcopenia and osteopenia in botulinum toxin immobilized mice.
abstract: 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.
  
  
  
  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).
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Biomedicine, Aarhus University, Wilhelm Meyers Allé 3, DK-8000 Aarhus C, Denmark.
authors.forename: J B
authors.initials: JB
authors.lastname: Vegger
authors.forename: A
authors.initials: A
authors.lastname: Brüel
authors.forename: A F
authors.initials: AF
authors.lastname: Dahlgaard
authors.forename: J S
authors.initials: JS
authors.lastname: Thomsen
mesh_terms: D015502:Absorptiometry, Photon; D000818:Animals; D001851:Bone Diseases, Metabolic / Q000235:genetics*; D001905:Botulinum Toxins / Q000633:toxicity; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D007103:Immobilization / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D009465:Neuromuscular Agents / Q000633:toxicity; D016133:Polymerase Chain Reaction; D011897:Random Allocation; D055948:Sarcopenia / Q000235:genetics*; D059467:Transcriptome; D055114:X-Ray Microtomography
chemical_list: D009465:Neuromuscular Agents; D001905:Botulinum Toxins