Effect of proton irradiation followed by hindlimb unloading on bone in mature mice: a model of long-duration spaceflight.
Effect of proton irradiation followed by hindlimb unloading on bone in mature mice: a model of long-duration spaceflight.
复制标题
DOI：
10.1016/j.bone.2012.07.001
复制
发表时间：
2012-10
期刊：
影响因子：
4.1
通讯作者：
Bateman, Ted A.
中科院分区：
文献类型：
--
作者：
Lloyd, Shane A.;Bandstra, Eric R.;Willey, Jeffrey S.;Riffle, Stephanie E.;Tirado-Lee, Leidamarie;Nelson, Gregory A.;Pecaut, Michael J.;Bateman, Ted A.
与微重力卸载有关的骨丢失已有详细记录;然而，与航天有关的辐射类型和剂量对骨骼系统的影响尚未明确界定。此外，卸荷和辐射的综合影响也没有受到太多关注。在本研究中，我们研究了质子照射后，通过后肢悬吊（HLS）的机械卸载小鼠的影响。将16周龄雌性C57 BL/6小鼠暴露于1戈伊质子或假照射程序（n=30/组）。一天后，每组中一半的小鼠经受四周的HLS或正常负荷条件。单独放射治疗（IRR）导致胫骨和股骨中约20%的松质骨体积分数（BV/TV）损失，对皮质骨室无影响。相反，在胫骨和股骨中，去负荷引起了松质骨（BV/TV损失60-70%）和皮质骨（皮质骨体积损失约20%）的显著更大损失，皮质骨强度相应降低。组织学分析和血清化学数据表明，在卸载小鼠破骨细胞介导的骨吸收水平增加，但IRR没有。HLS+IRR小鼠的骨小梁体积分数、连接密度和骨小梁数量的损失通常大于单纯卸载或照射。虽然卸载的持续时间可能掩盖了某些影响，骨骼对辐照和卸载的反应似乎是某些参数的添加剂。对长时间空间飞行的环境挑战进行适当建模，将有助于更好地了解与空间飞行相关的骨丢失的潜在机制，并制定有效的对策。
Bone loss associated with microgravity unloading is well documented; however, the effects of spaceflight-relevant types and doses of radiation on the skeletal system are not well defined. In addition, the combined effect of unloading and radiation has not received much attention. In the present study, we investigated the effect of proton irradiation followed by mechanical unloading via hindlimb suspension (HLS) in mice. Sixteen-week-old female C57BL/6 mice were either exposed to 1 Gy of protons or a sham irradiation procedure (n=30/group). One day later, half of the mice in each group were subjected to four weeks of HLS or normal loading conditions. Radiation treatment alone (IRR) resulted in approximately 20% loss of trabecular bone volume fraction (BV/TV) in the tibia and femur, with no effect in the cortical bone compartment. Conversely, unloading induced substantially greater loss of both trabecular bone (60–70% loss of BV/TV) and cortical bone (approximately 20% loss of cortical bone volume) in both the tibia and femur, with corresponding decreases in cortical bone strength. Histological analyses and serum chemistry data demonstrated increased levels of osteoclast-mediated bone resorption in unloaded mice, but not IRR. HLS+IRR mice generally experienced greater loss of trabecular bone volume fraction, connectivity density, and trabecular number than either unloading or irradiation alone. Although the duration of unloading may have masked certain effects, the skeletal response to irradiation and unloading appears to be additive for certain parameters. Appropriate modeling of the environmental challenges of long duration spaceflight will allow for a better understanding of the underlying mechanisms mediating spaceflight-associated bone loss and for the development of effective countermeasures.
登录
查看更多内容
影响因子：
3.4
作者：
Bandstra, Eric R.;Thompson, Raymond W.;Bateman, Ted A.
通讯作者：
Bateman, Ted A.
影响因子：
3.3
作者：
Lloyd, Shane A. J.;Travis, Neil D.;Bateman, Ted A.
通讯作者：
Bateman, Ted A.
DOI：
10.2187/bss.18.201
发表时间：
2004-12-01
期刊：
Uchu Seibutsu Kagaku
影响因子：
--
作者：
Ohnishi, Ken;Ohnishi, Takeo
通讯作者：
Ohnishi, Takeo
DOI：
10.1016/s0168-583x(01)00748-0
发表时间：
2001-09-01
影响因子：
1.3
作者：
Benton, ER;Benton, E
通讯作者：
Benton, E
影响因子：
6.2
作者：
Halloran, BP;Ferguson, VL;Majumdar, S
通讯作者：
Majumdar, S