Cytoplasmic reactive oxygen species and SOD1 regulate bone mass during mechanical unloading. (18th October 2013)

• Record Type: Journal Article
• Authors: Morikawa, Daichi; Nojiri, Hidetoshi; Saita, Yoshitomo; Kobayashi, Keiji; Watanabe, Kenji; Ozawa, Yusuke; Koike, Masato; Asou, Yoshinori; Takaku, Tomoiku; Kaneko, Kazuo; Shimizu, Takahiko
• Is Part Of: Journal of bone and mineral research. Volume 28:Number 11(2013:Nov.)
• Page Start: 2368
• Page End: 2380
• Publication Date: 2013-10-18
• Subjects: Bones -- Metabolism -- Periodicals; Mineral metabolism -- Periodicals; 612.392
• DOI: 10.1002/jbmr.1981
• Languages: English
• ISSNs: 0884-0431

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>ABSTRACT</title> <sec id="jbmr1981-sec-0001" sec-type="section"> <p>Oxidative stress contributes to the pathogenesis of age‐related diseases as well as bone fragility. Our previous study demonstrated that copper/zinc superoxide dismutase (<italic>Sod1</italic>)‐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 <italic>Sod1</italic> in bone tissue in a tail‐suspension experiment. We also reveal that <italic>Sod1</italic> 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 <italic>Sod1</italic> expression, suggesting that activating <italic>Sod1</italic> may be a preventive strategy for ameliorating mechanical unloading–induced bone loss. © 2013 American Society for Bone and Mineral Research.</p> </sec> </abstract>