title: The vestibular system is critical for the changes in muscle and bone induced by hypergravity in mice.
abstract: Gravity changes concurrently affect muscle and bone as well as induce alterations in vestibular signals. However, the role of vestibular signals in the changes in muscle and bone induced by gravity changes remains unknown. We therefore investigated the effects of vestibular lesions (VL) on the changes in muscle and bone induced by 3 g hypergravity for 4 weeks in C57BL/6J mice. Quantitative computed tomography analysis revealed that hypergravity increased muscle mass surrounding the tibia and trabecular bone mineral content, adjusting for body weight in mice. Hypergravity did not affect cortical bone and fat masses surrounding the tibia. Vestibular lesions blunted the increases in muscle and bone masses induced by hypergravity. Histological analysis showed that hypergravity elevated the cross-sectional area of myofiber in the soleus muscle. The mRNA levels of myogenic genes such as MyoD, Myf6, and myogenin in the soleus muscle were elevated in mice exposed to hypergravity. Vestibular lesions attenuated myofiber size and the mRNA levels of myogenic differentiation markers enhanced by hypergravity in the soleus muscle. Propranolol, a β-blocker, antagonized the changes in muscle induced by hypergravity. In conclusion, this study is the first to demonstrate that gravity changes affect muscle and bone through vestibular signals and subsequent sympathetic outflow in mice.
authors.affiliation: Department of Physiology and Regenerative Medicine, Kindai University Faculty of Medicine, Osakasayama, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kawao
authors.affiliation: Department of Physiology, Gifu University Graduate School of Medicine, Gifu, Japan Mouse Epigenetics Project, ISS/Kibo Experiment, Japan Aerospace Exploration Agency, Tsukuba, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Morita
authors.affiliation: Department of Physiology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Obata
authors.affiliation: Department of Physiology and Regenerative Medicine, Kindai University Faculty of Medicine, Osakasayama, Japan.
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Tamura
authors.affiliation: Life Science Research Institute, Kindai University, Osakasayama, Japan.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Okumoto
authors.affiliation: Department of Physiology and Regenerative Medicine, Kindai University Faculty of Medicine, Osakasayama, Japan hkaji@med.kindai.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kaji
mesh_terms: D000222:Adaptation, Physiological; D000319:Adrenergic beta-Antagonists / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D001835:Body Weight; D015519:Bone Density / Q000187:drug effects / Q000502:physiology*; D018471:Hypergravity / Q000009:adverse effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism*; D017570:MyoD Protein / Q000378:metabolism; D018006:Myogenic Regulatory Factors / Q000378:metabolism; D018008:Myogenin / Q000378:metabolism; D011433:Propranolol / Q000009:adverse effects / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D011897:Random Allocation; D013977:Tibia; D015837:Vestibular Diseases / Q000150:complications* / Q000503:physiopathology; D014722:Vestibule, Labyrinth / Q000378:metabolism / Q000502:physiology*
chemical_list: D000319:Adrenergic beta-Antagonists; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; C503801:Myog protein, mouse; D018006:Myogenic Regulatory Factors; D018008:Myogenin; D012333:RNA, Messenger; C063403:myogenic factor 6; D011433:Propranolol
keywords: Bone; gravity; muscle; vestibular system