Department of Radiation Oncology, University of California, Irvine, California, USA.
Radiat Res. 2010 Apr;173(4):494-504. doi: 10.1667/RR1754.1.
Space travel and prolonged bed rest cause bone loss due to musculoskeletal disuse. In space, radiation fields may also have detrimental consequences because charged particles traversing the tissues of the body can elicit a wide range of cytotoxic and genotoxic lesions. The effects of heavy-ion radiation exposure in combination with musculoskeletal disuse on bone cells and tissue are not known. To explore this, normally loaded 16-week-old male C57BL/6 mice were exposed to (56)Fe ions (1 GeV/nucleon) at doses of 0 cGy (sham), 10 cGy, 50 cGy or 2 Gy 3 days before tissue harvest. Additional mice were hindlimb unloaded by tail traction continuously for 1 week to simulate weightlessness and exposed to (56)Fe-ion radiation (0 cGy, 50 cGy, 2 Gy) 3 days before tissue harvest. Despite the short duration of this study, low-dose (10, 50 cGy) irradiation of normally loaded mice reduced trabecular volume fraction (BV/TV) in the proximal tibiae by 18% relative to sham-irradiated controls. Hindlimb unloading together with 50 cGy radiation caused a 126% increase in the number of TRAP(+) osteoclasts on cancellous bone surfaces relative to normally loaded, sham-irradiated controls. Together, radiation and hindlimb unloading had a greater effect on suppressing osteoblastogenesis ex vivo than either treatment alone. In sum, low-dose exposure to heavy ions (50 cGy) caused rapid cancellous bone loss in normally loaded mice and increased osteoclast numbers in hindlimb unloaded mice. In vitro irradiation also was more detrimental to osteoblastogenesis in bone marrow cells that were recovered from hindlimb unloaded mice compared to cells from normally loaded mice. Furthermore, irradiation in vitro stimulated osteoclast formation in a macrophage cell line (RAW264.7) in the presence of RANKL (25 ng/ml), showing that heavy-ion radiation can stimulate osteoclast differentiation even in the absence of osteoblasts. Thus heavy-ion radiation can acutely increase osteoclast numbers in cancellous tissue and, under conditions of musculoskeletal disuse, can enhance the sensitivity of bone cells, in particular osteoprogenitors, to the effects of radiation.
太空旅行和长时间卧床会导致骨骼流失，这是由于肌肉骨骼废用所致。在太空中，辐射场也可能产生有害影响，因为穿透身体组织的带电粒子会引起广泛的细胞毒性和遗传毒性损伤。目前尚不清楚重离子辐射暴露与肌肉骨骼废用对骨细胞和组织的综合影响。为了探索这一点，研究人员对正常负重的 16 周龄雄性 C57BL/6 小鼠进行了实验，在组织采集前 3 天，用 56Fe 离子（1GeV/核子）以 0 cGy（假照射）、10 cGy、50 cGy 或 2 Gy 的剂量对它们进行照射。此外，通过尾部牵引连续对部分小鼠进行后肢去负荷处理 1 周，以模拟失重状态，并在组织采集前 3 天用 56Fe 离子（0 cGy、50 cGy、2 Gy）对它们进行照射。尽管这项研究的持续时间很短，但对正常负重的小鼠进行低剂量（10、50 cGy）照射后，与假照射对照组相比，其胫骨近端的小梁体积分数（BV/TV）降低了 18%。后肢去负荷与 50 cGy 照射相结合，使松质骨表面的破骨细胞数量增加了 126%，与正常负重、假照射对照组相比。联合使用辐射和后肢去负荷对体外成骨细胞生成的抑制作用比单独使用任何一种处理都要强。总之，低剂量的重离子（50 cGy）照射会导致正常负重的小鼠快速出现松质骨丢失，并增加后肢去负荷小鼠的破骨细胞数量。与来自正常负重小鼠的细胞相比，从后肢去负荷小鼠中回收的骨髓细胞在体外照射后，成骨细胞生成也受到了更大的抑制。此外，在 RANKL（25ng/ml）存在的情况下，重离子辐射在巨噬细胞系（RAW264.7）中刺激破骨细胞形成，表明重离子辐射即使在没有成骨细胞的情况下也能刺激破骨细胞分化。因此，重离子辐射可以急性增加松质骨组织中的破骨细胞数量，并且在肌肉骨骼废用的情况下，可以增强骨细胞，特别是成骨前体细胞对辐射影响的敏感性。
