Lima Florence, Swift Joshua M, Greene Elisabeth S, Allen Matthew R, Cunningham David A, Braby Leslie A, Bloomfield Susan A
a Division of Nephrology, Bone and Mineral Metabolism, University of Kentucky, Lexington, Kentucky 40536.
b Department of Health and Kinesiology, Texas A&M University, College Station, Texas 77843.
Radiat Res. 2017 Oct;188(4):433-442. doi: 10.1667/RR14414.1. Epub 2017 Aug 3.
Exposure to high-dose ionizing radiation during medical treatment exerts well-documented deleterious effects on bone health, reducing bone density and contributing to bone growth retardation in young patients and spontaneous fracture in postmenopausal women. However, the majority of human radiation exposures occur in a much lower dose range than that used in the radiation oncology clinic. Furthermore, very few studies have examined the effects of low-dose ionizing radiation on bone integrity and results have been inconsistent. In this study, mice were irradiated with a total-body dose of 0.17, 0.5 or 1 Gy to quantify the early (day 3 postirradiation) and delayed (day 21 postirradiation) effects of radiation on bone microarchitecture and bone marrow stromal cells (BMSCs). Female BALBc mice (4 months old) were divided into four groups: irradiated (0.17, 0.5 and 1 Gy) and sham-irradiated controls (0 Gy). Micro-computed tomography analysis of distal femur trabecular bone from animals at day 21 after exposure to 1 Gy of X-ray radiation revealed a 21% smaller bone volume (BV/TV), 22% decrease in trabecular numbers (Tb.N) and 9% greater trabecular separation (Tb.Sp) compared to sham-irradiated controls (P < 0.05). We evaluated the differentiation capacity of bone marrow stromal cells harvested at days 3 and 21 postirradiation into osteoblast and adipocyte cells. Osteoblast and adipocyte differentiation was decreased when cells were harvested at day 3 postirradiation but enhanced in cells isolated at day 21 postirradiation, suggesting a compensatory recovery process. Osteoclast differentiation was increased in 1 Gy irradiated BMSCs harvested at day 3 postirradiation, but not in those harvested at day 21 postirradiation, compared to controls. This study provides evidence of an early, radiation-induced decrease in osteoblast activity and numbers, as well as a later recovery effect after exposure to 1 Gy of X-rays, whereas osteoclastogenesis was enhanced. A better understanding of the effects of radiation on osteoprogenitor cell populations could lead to more effective therapeutic interventions that protect bone integrity for individuals exposed to low-dose ionizing radiation.
在医学治疗过程中，暴露于高剂量电离辐射对骨骼健康具有已被充分证实的有害影响，会降低骨密度，导致年轻患者骨骼生长迟缓以及绝经后女性发生自发性骨折。然而，大多数人类辐射暴露发生在比放射肿瘤学临床使用剂量低得多的剂量范围内。此外，很少有研究考察低剂量电离辐射对骨骼完整性的影响，且结果并不一致。在本研究中，对小鼠进行全身剂量为0.17、0.5或1 Gy的照射，以量化辐射对骨微结构和骨髓基质细胞（BMSC）的早期（照射后第3天）和延迟（照射后第21天）影响。将4月龄雌性BALBc小鼠分为四组：照射组（0.17、0.5和1 Gy）和假照射对照组（0 Gy）。对暴露于1 Gy X射线辐射后第21天的动物股骨远端小梁骨进行微计算机断层扫描分析，结果显示与假照射对照组相比，骨体积（BV/TV）小21%，小梁数量（Tb.N）减少22%，小梁间距（Tb.Sp）增加9%（P < 0.05）。我们评估了照射后第3天和第21天收获的骨髓基质细胞向成骨细胞和脂肪细胞的分化能力。照射后第3天收获的细胞成骨细胞和脂肪细胞分化减少，但照射后第21天分离的细胞中分化增强，提示存在代偿性恢复过程。与对照组相比，照射后第3天收获的1 Gy照射的BMSC中破骨细胞分化增加，但照射后第21天收获的细胞中未增加。本研究提供了证据，表明暴露于1 Gy X射线后，早期辐射会导致成骨细胞活性和数量下降，随后出现恢复效应，而破骨细胞生成增强。更好地了解辐射对骨祖细胞群体的影响可能会带来更有效的治疗干预措施，以保护暴露于低剂量电离辐射的个体的骨骼完整性。
