Inhibition of Bone Loss and Muscle Atrophy by Dynamic Muscle Contractions With Rest Periods in a Functional Disuse Mouse Model

Author(s):  
Adiba Ali ◽  
Yi-Xian Qin

Osteoporosis, induced by aging and long-term disuse, often occurs together with muscle loss. Musculoskeletal disuse causes severe physiologic changes and it has been proposed the synergistic effects of muscle function and bone adaptation. Bone fluid flow has been shown to be induced during mechanical loading, and is proposed to be a critical mediator of bone adaptation. The skeletal muscle may serve as a muscle pump that may mediate bone mechanotransduction via modulation of intramedullary pressure. Thus, muscular stimulation is proposed to be used to simultaneously treat both muscle and bone loss, but the optimal parameters required for such treatment is unclear. Studies have separately investigated the optimal signal parameters for bone or muscle. Insertion of recovery periods during high frequency stimulations have shown potential to reduce muscle atrophy by minimizing fatigue and mimicking physiologic contractions, and demonstrated enhancement of bone remodeling. Our preliminary research has indicated that dynamic muscle contractions within an optimal frequency range can significantly recover disuse induced bone loss. However, the optimal rest periods required to prevent muscle fatigue during stimulations are not clear. The overall objective of this study was to evaluate optimized dynamic muscle stimulations at relatively high frequency, e.g., 20 Hz, and to test the role of varying the rest duration on muscle mass and bone morphology in a functional hind limb disuse mouse model.

Author(s):  
Yi-Xian Qin ◽  
Hoyan Lam ◽  
Murtaza Malbari

Musculoskeletal adaptations to aging and disuse environment have significant physiological effects on skeletal health, i.e., osteopenia and bone loss. Osteoporosis often occurs together with muscle loss. Such musculoskeletal complications cause severe physiologic changes and have been proposed the synergistic effects of muscle function and bone adaptation. The role of mechanobiology in the skeletal tissue may be closely related to load-induced transductive signals, e.g., bone fluid flow, which is proposed to be a critical mediator of bone and muscle adaptation. The skeletal muscle may serve as a muscle pump that may mediate bone mechanotransduction via modulation of intramedullary pressure. Muscular stimulation (MS) is proposed to be used to simultaneously treat both muscle and bone loss. Indeed, our recent data have demonstrated that high frequency, short duration stimulation can inhibit bone loss and muscle atrophy. Although 10 min dynamic loading can effectively attenuate bone loss, it cannot totally recover disuse osteopenia. The optimal parameters required for such treatment are unclear. Studies have separately investigated the optimal signal parameters for bone or muscle. Insertion of recovery periods during high frequency stimulations to extend the loading cycles have shown potential to reduce muscle atrophy by minimizing fatigue and mimicking physiologic contractions, and demonstrated enhancement of bone remodeling. The overall hypothesis for this study is that dynamic MS can enhance anabolic activity in bone, and inhibit bone loss in a functional disuse condition. Combined high frequency and sufficient loading cycle may be able to completely mitigate bone loss induced by disuse osteopenia.


Author(s):  
M. Hu ◽  
J. Cheng ◽  
S. Ferreri ◽  
F. Serra-Hsu ◽  
W. Lin ◽  
...  

Bone loss is a critical health problem of astronauts in long-term space missions. A growing number of evidence has pointed out bone fluid flow as a critical regulator in mechanotransductive signaling and bone adaptation. Intramedullary pressure (ImP) is a key mediator for bone fluid flow initiation and it influences the osteogenic signals within the skeleton. The potential ImP-induced bone fluid flow then triggers bone adaptation [1]. Previous in vivo study has demonstrated that ImP induced by oscillatory electrical stimulations can effectively mitigate disuse osteopenia in a frequency-dependent manner in a disuse rat model [2, 3]. In order to develop the translational potentials of ImP, a non-invasive intervention with direct fluid flow coupling is necessary to develop new treatments for microgravity-induced osteopenia/osteoporosis.


Author(s):  
Y. X. Qin ◽  
M. Hu ◽  
F. Serra-Hsu ◽  
J. Cheng ◽  
S. Ferreri ◽  
...  

Osteoporosis gives rise to fragile bones that have higher fracture risks due to diminished bone mass and altered bone microarchitecture [1]. Mechanical loading mediated bone adaptation has demonstrated promising potentials as a non-pharmacological alteration for both osteogenic response and attenuation of osteopenia [2]. Intramedullary pressure (ImP) has been proposed as a key factor for fluid flow initiation and mechanotransductive signal inductions in bone. It is also suggested that integration of strain signals over time allows low-level mechanical strain in the skeleton to trigger osteogenic activities. The potential bone fluid flow induced by strain and ImP mediates adaptive responses in the skeleton [3]. Previous in vivo studies using oscillatory electrical stimulations showed that dynamic muscle contractions can generate ImP and bone strain to mitigate disuse osteopenia in a frequency-dependent manner. To apply ImP alteration as a means for bone fluid flow regulation, it may be necessary to develop a new method that could couple external loading with internal bone fluid flow. In order to further study the direct effect of ImP on bone adaptation, it was hypothesized that external dynamic hydraulic stimulation (DHS) can generate ImP with minimal strain in a frequency-dependent manner. The aim of this study was to evaluate the immediate effects on local and distant ImP and bone strain induced by a novel, non-invasive dynamic external pressure stimulus in response to a range of loading frequencies.


2021 ◽  
Vol 138 ◽  
pp. 111503
Author(s):  
Chiaki Yamada ◽  
Anny Ho ◽  
Juliet Akkaoui ◽  
Christopher Garcia ◽  
Carolina Duarte ◽  
...  

Heliyon ◽  
2021 ◽  
Vol 7 (8) ◽  
pp. e07828
Author(s):  
Michael M. Schündeln ◽  
Jakob Höppner ◽  
Felix L. Meyer ◽  
Wiebke Schmuck ◽  
Max D. Kauther ◽  
...  
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2009 ◽  
Vol 36 (5) ◽  
pp. 406-410 ◽  
Author(s):  
David Polak ◽  
Asaf Wilensky ◽  
Lior Shapira ◽  
Amal Halabi ◽  
Dita Goldstein ◽  
...  

Bone ◽  
2018 ◽  
Vol 109 ◽  
pp. 49-55 ◽  
Author(s):  
Kavitha Ranganathan ◽  
Xiaowei Hong ◽  
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Joe Habbouche ◽  
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2018 ◽  
Vol 120 (6) ◽  
pp. 3077-3084 ◽  
Author(s):  
Ellen T. Koch ◽  
Cameron L. Woodard ◽  
Lynn A. Raymond

Glutamate is the main excitatory neurotransmitter in the brain, and impairments in its signaling are associated with many neurological disorders, including Huntington’s disease (HD). Previous studies in HD mouse models demonstrate altered glutamate receptor distribution and signaling at cortico-striatal synapses, and some studies suggest that glutamate release is altered; however, traditional methods to study synaptic glutamate release are indirect or have poor temporal resolution. Here we utilize iGluSnFR, a modified green fluorescent protein reporter for real-time imaging of glutamate transmission, to study presynaptic modulation of cortical glutamate release in the striatum of the YAC128 HD mouse model. We determined that iGluSnFR can be used to accurately measure short- and long-term changes in glutamate release caused by modulation of extracellular Ca2+ levels, activation of presynaptic receptors, and high-frequency stimulation (HFS) protocols. We also confirmed a difference in the expression of HFS-induced long-term depression in YAC128. Together, this research demonstrates the utility of iGluSnFR in studying presynaptic modulation of glutamate release in healthy mice and disease models that display impairments in glutamate signaling. NEW & NOTEWORTHY We use iGluSnFR to directly assess presynaptic modulation of cortico-striatal glutamate release in brain slice and compare changes in glutamate release between wild type and a Huntington’s disease mouse model, YAC128. We observed reductions in glutamate release after low extracellular Ca2+ and activation of various presynaptic receptors. We also demonstrate a presynaptic mechanism of reduced glutamate release in high-frequency stimulation-induced long-term depression and show this to be altered in YAC128.


CHEST Journal ◽  
1992 ◽  
Vol 102 (4) ◽  
pp. 1251-1257 ◽  
Author(s):  
Kunihiko Iizuka ◽  
Kunio Dobashi ◽  
Shinobu Houjou ◽  
Hiromi Sakai ◽  
Kouichi Itoh ◽  
...  

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