Oxidative stress and gamma radiation-induced cancellous bone loss with musculoskeletal disuse
Oxidative stress and gamma radiation-induced cancellous bone loss with musculoskeletal disuse
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DOI：
10.1152/japplphysiol.00294.2009
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发表时间：
2010-01-01
影响因子：
3.3
通讯作者：
Globus, Ruth K.
中科院分区：
文献类型：
--
作者：
Kondo, Hisataka;Yumoto, Kenji;Globus, Ruth K.
首页--期刊主要分类--期刊细介绍--期刊题录与文摘--期刊详细文摘内容氧化应激和伽马辐射导致的松质骨丢失和肌肉骨骼的废弃。应用生理学杂志108：152-161,2010。2009年10月29日首次出版；doi：10.1152/japplPhysiol.00294.2009。-宇航员在失重状态下暴露在太空中的辐射可能会导致随后的骨质流失。青春期后小鼠的伽玛射线照射会迅速增加骨吸收破骨细胞的数量，并导致松质组织中的骨丢失；与氧化应激相关的骨骼疾病也会发生类似的变化。因此，我们假设氧化应激增加介导了辐射引起的骨丢失，肌肉骨骼的废弃改变了松质组织对辐射暴露的敏感性。4个月龄的雄性C57BL/6小鼠分别通过后肢卸载(1或2周)或全身伽玛照射(1或2 GyCs-137)来停止肌肉骨骼，使胫骨近端和腰椎的松质骨体积分数减少。在正常负荷和后肢去负荷的小鼠中，辐射诱导的胫骨和腰椎急性松质骨丢失的程度相似。同样，与正常负荷的小鼠相比，照射后胫骨破骨细胞表面增加46%，后肢卸载增加47%，后肢卸载增加%。照射，而不是后肢卸载，降低了骨髓细胞的活力，增加了细胞的凋亡率，并对矿化组织内的脂质造成了氧化损伤。辐射还能刺激骨髓细胞产生活性氧。此外，注射抗氧化剂α-硫辛酸可以减轻辐射引起的急性骨丢失。总之，这些结果表明，停用和伽马射线单独或联合使用，会导致类似程度的急性松质骨丢失，并具有共同的骨吸收增加的细胞学机制。此外，辐射可能会增加破骨细胞的数量，并通过增加活性氧的产生和随后的氧化损伤来增加急性骨丢失的程度，这意味着不同的分子机制。α-硫辛酸保护松质组织免受辐射的有害影响，这一发现与宇航员和放射治疗患者有潜在的相关性。
Kondo H, Yumoto K, Alwood JS, Mojarrab R, Wang A, Almeida EA, Searby ND, Limoli CL, Globus RK. Oxidative stress and gamma radiation-induced cancellous bone loss with musculoskeletal disuse. J Appl Physiol 108: 152-161, 2010. First published October 29, 2009; doi:10.1152/japplphysiol.00294.2009.-Exposure of astronauts in space to radiation during weightlessness may contribute to subsequent bone loss. Gamma irradiation of postpubertal mice rapidly increases the number of bone-resorbing osteoclasts and causes bone loss in cancellous tissue; similar changes occur in skeletal diseases associated with oxidative stress. Therefore, we hypothesized that increased oxidative stress mediates radiation-induced bone loss and that musculoskeletal disuse changes the sensitivity of cancellous tissue to radiation exposure. Musculoskeletal disuse by hindlimb unloading (1 or 2 wk) or total body gamma irradiation (1 or 2 Gy of Cs-137) of 4-mo-old, male C57BL/6 mice each decreased cancellous bone volume fraction in the proximal tibiae and lumbar vertebrae. The extent of radiation-induced acute cancellous bone loss in tibiae and lumbar vertebrae was similar in normally loaded and hindlimb-unloaded mice. Similarly, osteoclast surface in the tibiae increased 46% as a result of irradiation, 47% as a result of hindlimb unloading, and 64% as a result of irradiation + hindlimb unloading compared with normally loaded mice. Irradiation, but not hindlimb unloading, reduced viability and increased apoptosis of marrow cells and caused oxidative damage to lipids within mineralized tissue. Irradiation also stimulated generation of reactive oxygen species in marrow cells. Furthermore, injection of alpha-lipoic acid, an antioxidant, mitigated the acute bone loss caused by irradiation. Together, these results showed that disuse and gamma irradiation, alone or in combination, caused a similar degree of acute cancellous bone loss and shared a common cellular mechanism of increased bone resorption. Furthermore, irradiation, but not disuse, may increase the number of osteoclasts and the extent of acute bone loss via increased reactive oxygen species production and ensuing oxidative damage, implying different molecular mechanisms. The finding that alpha-lipoic acid protected cancellous tissue from the detrimental effects of irradiation has potential relevance to astronauts and radiotherapy patients.