The influence of therapeutic radiation on the patterns of bone marrow in ovary-intact and ovariectomized mice.

The influence of therapeutic radiation on the patterns of bone marrow in ovary-intact and ovariectomized mice.
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DOI:
10.1371/journal.pone.0042668
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Yee D
Yee D
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Hui SK;Sharkey L;Kidder LS;Zhang Y;Fairchild G;Coghill K;Xian CJ;Yee D

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骨髓的功能成分(即,造血和基质群)和邻近的骨传统上作为不同的实体而不是整合的系统被不完全地评估。我们在卵巢功能存在或不存在的情况下,使用医学相关的辐射模型在体内扰动该系统,以了解整合的组织相互作用。卵巢完整和卵巢切除小鼠的尾部骨骼接受不照射或单次16戈伊照射(I±R,OVX±R)。评估骨髓脂肪、造血细胞构成和松质骨体积分数(BV/TV %)。30天后,单独卵巢切除术未显著降低未照射小鼠的骨髓细胞构成(OVX−R vs. I−R,p =0.8445);然而,它损害了辐射暴露后骨髓的造血恢复(OVX+R vs. I+R,p= 0.0092)。    与单独的任一因素相比,放疗和OVX的组合显著增加骨髓脂肪(p = 0.0062)。  协同效应在造血骨髓细胞减少方面也很明显(p = 0.0661);但在BV/TV%变化方面不存在协同效应(p = 0.2520)。    观察到骨髓脂肪与造血细胞和骨体积之间的预期负相关关系。有趣的是,与OVX小鼠相比,完整小鼠表现出造血细胞减少一倍,骨髓脂肪扩张一个给定单位的骨丢失程度增加十倍。在对小鼠进行临床相关局灶性辐射暴露之前进行卵巢切除术,加剧了骨髓空间中的辐射后脂肪积聚,但减弱了骨丢失和造血抑制。在正常偶联的骨和骨髓结构域之间的稳态关系中,OVX似乎改变了反馈机制。需要证实这种非线性现象(可能是由于不同的辐射敏感性)和证明作用机制,以提供减少辐射对暴露组织影响的策略。
The functional components of bone marrow (i.e., the hematopoietic and stromal populations) and the adjacent bone have traditionally been evaluated incompletely as distinct entities rather than the integrated system. We perturbed this system in vivo using a medically relevant radiation model in the presence or absence of ovarian function to understand integrated tissue interaction. Ovary-intact and ovariectomized mice underwent either no radiation or single fractional 16 Gy radiation to the caudal skeleton (I±R, OVX±R). Marrow fat, hematopoietic cellularity, and cancellous bone volume fraction (BV/TV %) were assessed. Ovariectomy alone did not significantly reduce marrow cellularity in non-irradiated mice (OVX−R vs. I−R, p = 0.8445) after 30 days; however it impaired the hematopoietic recovery of marrow following radiation exposure (OVX+R vs. I+R, p = 0.0092). The combination of radiation and OVX dramatically increases marrow fat compared to either factor alone (p = 0.0062). The synergistic effect was also apparent in the reduction of hematopoietic marrow cellularity (p = 0.0661); however it was absent in BV/TV% changes (p = 0.2520). The expected inverse relationship between marrow adiposity vs. hematopoietic cellularity and bone volume was observed. Interestingly compared with OVX mice, intact mice demonstrated double the reduction in hematopoietic cellularity and a tenfold greater degree of bone loss for a given unit of expansion in marrow fat. Ovariectomy prior to delivery of a clinically-relevant focal radiation exposure in mice, exacerbated post-radiation adipose accumulation in the marrow space but blunted bone loss and hematopoietic suppression. In the normally coupled homeostatic relationship between the bone and marrow domains, OVX appears to alter feedback mechanisms. Confirmation of this non-linear phenomenon (presumably due to differential radiosensitivity) and demonstration of the mechanism of action is needed to provide strategies to diminish the effect of radiation on exposed tissues.
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