Cytoplasmic reactive oxygen species and SOD1 regulate bone mass during mechanical unloading

• Published in: Journal of bone and mineral research 2013-11, Vol.28 (11), p.2368-2380
• Main Authors: Morikawa, Daichi, Nojiri, Hidetoshi, Saita, Yoshitomo, Kobayashi, Keiji, Watanabe, Kenji, Ozawa, Yusuke, Koike, Masato, Asou, Yoshinori, Takaku, Tomoiku, Kaneko, Kazuo, Shimizu, Takahiko
• Format: Article
• Language: English
• Subjects: Animals; ASCORBIC ACID; Biomarkers - metabolism; Bone and Bones - enzymology; Bone and Bones - pathology; Bone and Bones - physiopathology; BONE LOSS; Bone Marrow Cells - metabolism; Bone Resorption - drug therapy; Bone Resorption - pathology; Bone Resorption - physiopathology; COPPER/ZINC SUPEROXIDE DISMUTASE; Cytoplasm - enzymology; Intracellular Space - metabolism; Male; MECHANICAL STRESS; Mice; Mice, Inbred C57BL; Organ Size; Osteogenesis; OXIDATIVE STRESS; Reactive Oxygen Species - metabolism; Stress, Mechanical; Superoxide Dismutase - deficiency; Superoxide Dismutase - metabolism; Up-Regulation; VITAMIN C (VC; Weight-Bearing
• ISSN: 0884-0431; 1523-4681
• DOI: 10.1002/jbmr.1981

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. © 2013 American Society for Bone and Mineral Research.