title: Cytoplasmic reactive oxygen species and SOD1 regulate bone mass during mechanical unloading.
abstract: Oxidative stress contributes to the pathogenesis of age-related diseases as well as bone fragility. Our previous study demonstrated that copper/zinc superoxide dismutase (Sod1)-deficient mice exhibit the induction of intracellular reactive oxygen species (ROS) and bone fragility resulting from low-turnover bone loss and impaired collagen cross-linking (Nojiri et al. J Bone Miner Res. 2011;26:2682-94). Mechanical stress also plays an important role in the maintenance of homeostasis in bone tissue. However, the molecular links between oxidative and mechanical stresses in bone tissue have not been fully elucidated. We herein report that mechanical unloading significantly increased intracellular ROS production and the specific upregulation of Sod1 in bone tissue in a tail-suspension experiment. We also reveal that Sod1 loss exacerbated bone loss via reduced osteoblastic abilities during mechanical unloading. Interestingly, we found that the administration of an antioxidant, vitamin C, significantly attenuated bone loss during unloading. These results indicate that mechanical unloading, in part, regulates bone mass via intracellular ROS generation and the Sod1 expression, suggesting that activating Sod1 may be a preventive strategy for ameliorating mechanical unloading-induced bone loss.
authors.affiliation: Department of Advanced Aging Medicine, Chiba University Graduate School of Medicine, Chiba, Japan; Department of Orthopaedics, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Daichi
authors.initials: D
authors.lastname: Morikawa
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Nojiri
authors.forename: Yoshitomo
authors.initials: Y
authors.lastname: Saita
authors.forename: Keiji
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Kenji
authors.initials: K
authors.lastname: Watanabe
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Ozawa
authors.forename: Masato
authors.initials: M
authors.lastname: Koike
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Asou
authors.forename: Tomoiku
authors.initials: T
authors.lastname: Takaku
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kaneko
authors.forename: Takahiko
authors.initials: T
authors.lastname: Shimizu
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism; D001862:Bone Resorption / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D001842:Bone and Bones / Q000201:enzymology* / Q000473:pathology* / Q000503:physiopathology; D003593:Cytoplasm / Q000201:enzymology*; D042541:Intracellular Space / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size; D010012:Osteogenesis; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013314:Stress, Mechanical; D013482:Superoxide Dismutase / Q000172:deficiency / Q000378:metabolism*; D015854:Up-Regulation; D016474:Weight-Bearing
chemical_list: D015415:Biomarkers; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase
keywords: ASCORBIC ACID); BONE LOSS; COPPER/ZINC SUPEROXIDE DISMUTASE; MECHANICAL STRESS; OXIDATIVE STRESS; VITAMIN C (VC