TY - JOUR
T1 - Local cyclical compression modulates macrophage function in situ and alleviates immobilization-induced muscle atrophy
AU - Saitou, Kumiko
AU - Tokunaga, Masakuni
AU - Yoshino, Daisuke
AU - Sakitani, Naoyoshi
AU - Maekawa, Takahiro
AU - Ryu, Youngjae
AU - Nagao, Motoshi
AU - Nakamoto, Hideki
AU - Saito, Taku
AU - Kawanishi, Noriaki
AU - Suzuki, Katsuhiko
AU - Ogata, Toru
AU - Makuuchi, Michiru
AU - Takashima, Atsushi
AU - Sawada, Keisuke
AU - Kawamura, Shunsuke
AU - Nakazato, Koichi
AU - Kouzaki, Karina
AU - Harada, Ichiro
AU - Ichihara, Yoshinori
AU - Sawada, Yasuhiro
N1 - Funding Information:
This work was in part supported by Intramural Research Fund from the Japanese Ministry of Health, Labour and Welfare; Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (to T.O. and Y.S.); MEXT-Supported Program for the Strategic Research Foundation at Private Universities, 2015–2019 from the Japanese Ministry of Education, Culture, Sports, Science and Technology [S1511017]; and EMBO Long-Term Fellowship [ALTF 1130-2017 (to S.K.).
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/10/1
Y1 - 2018/10/1
N2 - Physical inactivity gives rise to numerous diseases and organismal dysfunctions, particularly those related to aging. Musculoskeletal disorders including muscle atrophy, which can result from a sedentary lifestyle, aggravate locomotive malfunction and evoke a vicious circle leading to severe functional disruptions of vital organs such as the brain and cardiovascular system. Although the significance of physical activity is evident, molecular mechanisms behind its beneficial effects are poorly understood. Here, we show that massage-like mechanical interventions modulate immobilization-induced pro-inflammatory responses of macrophages in situ and alleviate muscle atrophy. Local cyclical compression (LCC) on mouse calves, which generates intramuscular pressure waves with amplitude of 50 mmHg, partially restores the myofiber thickness and contracting forces of calf muscles that are decreased by hindlimb immobilization. LCC tempers the increase in the number of cells expressing pro-inflammatory proteins, tumor necrosis factor-α and monocyte chemoattractant protein-1 (MCP-1), including macrophages in situ. The reversing effect of LCC on immobilization-induced thinning of myofibers is almost completely nullified when macrophages recruited from circulating blood are depleted by administration of clodronate liposomes. Furthermore, application of pulsatile fluid shear stress, but not hydrostatic pressure, reduces the expression of MCP-1 in macrophages in vitro. Together with the LCC-induced movement of intramuscular interstitial fluid detected by μCT analysis, these results suggest that mechanical modulation of macrophage function is involved in physical inactivity-induced muscle atrophy and inflammation. Our findings uncover the implication of mechanosensory function of macrophages in disuse muscle atrophy, thereby opening a new path to develop a novel therapeutic strategy utilizing mechanical interventions.
AB - Physical inactivity gives rise to numerous diseases and organismal dysfunctions, particularly those related to aging. Musculoskeletal disorders including muscle atrophy, which can result from a sedentary lifestyle, aggravate locomotive malfunction and evoke a vicious circle leading to severe functional disruptions of vital organs such as the brain and cardiovascular system. Although the significance of physical activity is evident, molecular mechanisms behind its beneficial effects are poorly understood. Here, we show that massage-like mechanical interventions modulate immobilization-induced pro-inflammatory responses of macrophages in situ and alleviate muscle atrophy. Local cyclical compression (LCC) on mouse calves, which generates intramuscular pressure waves with amplitude of 50 mmHg, partially restores the myofiber thickness and contracting forces of calf muscles that are decreased by hindlimb immobilization. LCC tempers the increase in the number of cells expressing pro-inflammatory proteins, tumor necrosis factor-α and monocyte chemoattractant protein-1 (MCP-1), including macrophages in situ. The reversing effect of LCC on immobilization-induced thinning of myofibers is almost completely nullified when macrophages recruited from circulating blood are depleted by administration of clodronate liposomes. Furthermore, application of pulsatile fluid shear stress, but not hydrostatic pressure, reduces the expression of MCP-1 in macrophages in vitro. Together with the LCC-induced movement of intramuscular interstitial fluid detected by μCT analysis, these results suggest that mechanical modulation of macrophage function is involved in physical inactivity-induced muscle atrophy and inflammation. Our findings uncover the implication of mechanosensory function of macrophages in disuse muscle atrophy, thereby opening a new path to develop a novel therapeutic strategy utilizing mechanical interventions.
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U2 - 10.1042/CS20180432
DO - 10.1042/CS20180432
M3 - Article
C2 - 30209036
AN - SCOPUS:85054897681
SN - 0143-5221
VL - 132
SP - 2147
EP - 2161
JO - Clinical Science
JF - Clinical Science
IS - 19
ER -