Simulated microgravity‐induced oxidative stress and loss of osteogenic potential of osteoblasts can be prevented by protection of primary cilia

作者：Lu‐Wei Miao, T.J. Liu, Yue‐Hong Sun, Nan Cai, Ying‐Ying Xuan, Zhenlong Wei, Bing‐Bing Cui, Linlin Jing, Huiping Ma, Cory J. Xian, Jufang Wang, Yuhai Gao, Keming Chen · 发表于：Journal of Cellular Physiology · 年份：2023 · DOI：10.1002/jcp.31127 · 被引用次数：21 · 研究领域：Spaceflight effects on biology、Genetics, Aging, and Longevity in Model Organisms、Medical and Biological Ozone Research

Abstract Oxidative stress has been considered to be closely related to spaceflight‐induced bone loss; however, mechanism is elusive and there are no effective countermeasures. Using cultured rat calvarial osteoblasts exposed to microgravity simulated by a random positioning machine, this study addressed the hypotheses that microgravity‐induced shortening of primary cilia leads to oxidative stress and that primary cilium protection prevents oxidative stress and osteogenesis loss. Microgravity was found to induce oxidative stress (as represented by increased levels of reactive oxygen species (ROS) and malondialdehyde production, and decreased activities of antioxidant enzymes), which was perfectly replicated in osteoblasts growing in NG with abrogated primary cilia (created by transfection of an interfering RNA), suggesting the possibility that shortening of primary cilia leads to oxidative stress. Oxidative stress was accompanied by mitochondrial dysfunction (represented by increased mitochondrial ROS and decreased mitochondrial membrane potential) and intracellular Ca 2+ overload, and the latter was found to be caused by increased activity of Ca 2+ channel transient receptor potential vanilloid 4 (TRPV4), as also evidenced by TRPV4 agonist GSK1016790A‐elicited Ca 2+ influx. Supplementation of HC‐067047, a specific antagonist of TRPV4, attenuated microgravity‐induced mitochondrial dysfunction, oxidative stress, and osteogenesis loss. Although TRPV4 was found localized in prima...