Vibration platform for mice to deliver precise, low intensity mechanical signals to the musculoskeleton.

OBJECTIVE: Low intensity vibration as a therapeutic and training modality has received increased attention despite the lack of clear mechanistic pathways. Thus, to determine mechanisms underpinning vibration-induced musculoskeletal adaptations, a vibration platform for mice was designed, constructed, and validated. METHODS: Critical aspects of the platform include use of off-the-shelf components to (1) tailor individual parameter selection (acceleration and frequency), (2) produce low error across the plate's surface and throughout the range of vibration parameters, and (3) utilize accelerometer feedback to ensure fidelity within and between bouts of vibration. The vibration device is controlled by a centrally-mounted linear actuator on the underside of the platform that is modulated by accelerometer feedback. RESULTS: Triaxial accelerometers confirmed that vibrations were purely vertical and acceleration responses were within 5% of target stimuli for all accelerations (0.2-1.0 g) and frequencies (25-90 Hz). The platform produced acceleration responses with ≤4% error between 25-90 Hz. Vibration modes were not detected indicating that the circular plate produced uniform stimuli across the platform (error ≤1.1%, P≥0.23) and mouse body mass did not affect the platform's performance (P≥0.43). CONCLUSIONS: Our vibration device for mice improves upon existing devices and enables precise, low intensity mechanical signals to be applied with confidence.

Musculoskeletal response of dystrophic mice to short term, low intensity, high frequency vibration.

OBJECTIVES: We aimed to identify parameters of low-intensity vibration that initiate the greatest osteogenic response in dystrophin-deficient mice and determine vibration safety for diseased muscle in three separate studies. METHODS: Study1: Mdx mice were randomized into seven vibration treatments and 14 d later, plasma osteocalcin and tibial osteogenic gene expression were compared among treatments. Study2: Three days of vibration was compared to other modalities known to elicit muscle injury in mdx mice. Study3: Dystrophic mice with more severe phenotypes due to altered utrophin were subjected to 7 d vibration to determine if muscle injury was induced. Muscle torque and genes associated with inflammation and myogenesis were assessed in Studies 2-3. RESULTS: Two sets of parameters (45 Hz 0.6 g and 90 Hz 0.6 g) evoked osteogenic responses. 45 Hz upregulated alkaline phosphatase and tended to upregulate osteoprotegerin without altering RANKL, and 90 Hz simultaneously upregulated osteprotegerin and RANKL. Thus, subsequent muscle studies utilized 45 Hz. Vibration for 3 or 7 d was not injurious to dystrophic muscle as shown by the lack of differences between vibrated and non-vibrated mice in torque and gene expression. CONCLUSIONS: Results indicate that vibration at 45 Hz and 0.6 g is safe for dystrophic muscle and may be a therapeutic modality to improve musculoskeletal health in DMD.

Prednisolone treatment and restricted physical activity further compromise bone of mdx mice.

OBJECTIVES: The purpose of this study was to determine the extent to which prednisolone treatment and restricted physical activity caused deleterious changes in inherently compromised mdx bone. METHODS: Four week-old male mdx mice (n=36) were treated for 8-wk either with or without prednisolone (0.8-1.3 mg/kg/d) and were housed in traditional or small cages (restricted activity). Tibial bone strength, geometry, and intrinsic material properties were assessed at the mid-shaft by three-point bending and micro-computed tomography (µCT). RESULTS: Three-point bending results showed that both prednisolone and restricted activity reduced bone strength (7%), however stiffness was only reduced in restricted-activity mice. µCT analyses showed that cortical bone area and cortical thickness were 13% smaller in restricted-activity mice, and may have accounted for their compromised bone strength. Intrinsic material properties, including volumetric bone mineral density (vBMD) and modulus of elasticity, were not impacted by either treatment, however, vBMD tended to be lower in restricted-activity mice (p=0.06). CONCLUSIONS: These data show that prednisolone treatment and restricted physical activity independently accentuate reductions in the strength and geometry of mdx bone, but do not influence intrinsic material properties.