Simulated Galactic Cosmic Rays Modify Mitochondrial Metabolism in Osteoclasts, Increase Osteoclastogenesis and Cause Trabecular Bone Loss in Mice.
Simulated Galactic Cosmic Rays Modify Mitochondrial Metabolism in Osteoclasts, Increase Osteoclastogenesis and Cause Trabecular Bone Loss in Mice.
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DOI：
10.3390/ijms222111711
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发表时间：
2021-10-28
影响因子：
5.6
通讯作者：
Aykin-Burns N
中科院分区：
文献类型：
--
作者：
Kim HN;Richardson KK;Krager KJ;Ling W;Simmons P;Allen AR;Aykin-Burns N
太空是一个高压环境。宇航员离开地球磁场时的一个主要风险因素是暴露于银河宇宙射线（GCR）的电离辐射。在太空中哺乳动物的解剖学和生理学会发生一些不利的变化，包括骨质流失。在这项研究中，我们评估了简化的GCR暴露对骨骼健康的影响。暴露于0.5戈伊全身模拟GCR后3个月，从9月龄雄性小鼠收集血液、骨髓和组织。我们的细胞和组织分析的主要发现是：（1）GCR诱导成年小鼠股骨骨小梁丢失，但对脊柱骨小梁没有影响。(2)GCR增加循环破骨细胞分化标志物和破骨细胞形成，但不改变新骨形成或成骨细胞分化。(3)稳态水平的线粒体活性氧，线粒体和非线粒体呼吸增加后，GCR暴露在前破骨细胞的线粒体质量没有任何变化。(4)前破骨细胞中GCR暴露后底物利用的改变表明线粒体的代谢重新布线。总之，靶向辐射介导的破骨细胞的线粒体代谢重编程可以被推测为太空旅行诱导的骨丢失的可行的治疗策略。
Space is a high-stress environment. One major risk factor for the astronauts when they leave the Earth’s magnetic field is exposure to ionizing radiation from galactic cosmic rays (GCR). Several adverse changes occur in mammalian anatomy and physiology in space, including bone loss. In this study, we assessed the effects of simplified GCR exposure on skeletal health in vivo. Three months following exposure to 0.5 Gy total body simulated GCR, blood, bone marrow and tissue were collected from 9 months old male mice. The key findings from our cell and tissue analysis are (1) GCR induced femoral trabecular bone loss in adult mice but had no effect on spinal trabecular bone. (2) GCR increased circulating osteoclast differentiation markers and osteoclast formation but did not alter new bone formation or osteoblast differentiation. (3) Steady-state levels of mitochondrial reactive oxygen species, mitochondrial and non-mitochondrial respiration were increased without any changes in mitochondrial mass in pre-osteoclasts after GCR exposure. (4) Alterations in substrate utilization following GCR exposure in pre-osteoclasts suggested a metabolic rewiring of mitochondria. Taken together, targeting radiation-mediated mitochondrial metabolic reprogramming of osteoclasts could be speculated as a viable therapeutic strategy for space travel induced bone loss.
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影响因子：
3.6
作者：
Baskar R;Lee KA;Yeo R;Yeoh KW
通讯作者：
Yeoh KW
影响因子：
16.6
作者：
Brunner, Julia S.;Vulliard, Loan;Schabbauer, Gernot
通讯作者：
Schabbauer, Gernot
影响因子：
8
作者：
Fujiwara, Toshifumi;Ye, Shiqiao;Zhao, Haibo
通讯作者：
Zhao, Haibo
影响因子：
120.7
作者：
Baxter, NN;Habermann, EB;Virnig, BA
通讯作者：
Virnig, BA
DOI：
10.1093/gerona/glt079
发表时间：
2013-10-01
影响因子：
5.1
作者：
Almeida, Maria;OBrien, Charles A.
通讯作者：
OBrien, Charles A.