The age-dependent effect of high-dose X-ray radiation on NFκB signaling, structure, and mechanical behavior of the intervertebral disc
The age-dependent effect of high-dose X-ray radiation on NFκB signaling, structure, and mechanical behavior of the intervertebral disc
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DOI：
10.1080/03008207.2019.1703963
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发表时间：
2019-12-27
影响因子：
2.9
通讯作者：
Tang, Simon Y.
中科院分区：
文献类型：
--
作者：
Liu, Jennifer W.;Piersma, Sytse;Tang, Simon Y.
目的：电离辐射损伤组织，并引起多器官系统的炎症反应。我们研究了高剂量X射线辐射对椎间盘（IVD）分子炎症和力学功能的影响。研究方法：从1月龄、6月龄和16月龄NF κ B-荧光素酶报告基因小鼠和6月龄髓样分化因子88（MyD 88）缺失小鼠中提取的含有椎骨-IVD-椎骨结构的功能性脊柱单位（FSU）。在培养预处理后，FSU经受20 Gys的单剂量电离X射线辐射，然后监测NF κ B表达。然后使用动态压缩、糖胺聚糖（GAG）定量和组织学分析对IVD进行机械测试。结果：1月龄FSU在照射后1 d内NF κ B驱动的荧光素酶活性显著升高。6个月龄的FSU显示出增加的NF κ B活性持续3天，而16个月龄的FSU在整个10天的培养期内持续升高的NF κ B活性水平。所有照射组均显示椎间盘高度、GAG含量、机械功能和结构变化的显著损失。MyD 88的消融减弱了辐射介导的NF κ B信号传导，并保留了GAG含量以及IVD的结构和机械性能。结论：这些结果表明，高剂量辐射影响IVD的NF κ B依赖性炎症过程，随后导致功能恶化。通过MyD 88消融阻断NF κ B的反式激活潜力可保护FSU的结构和机械功能。在易受职业和医疗照射的个体中，应考虑辐射对IVD体内平衡的长期影响。
Purpose: Ionizing radiation damages tissue and provokes inflammatory responses in multiple organ systems. We investigated the effects of high-dose X-ray radiation on the molecular inflammation and mechanical function of the intervertebral disc (IVD). Methods: Functional spine units (FSUs) containing the vertebrae-IVDs-vertebrae structure extracted from 1-month, 6-month, and 16-month-old NF kappa B-luciferase reporter mice and from 6-month-old myeloid differentiation factor 88 (MyD88)-null mice. After a preconditioning period in culture, the FSUs were subjected a single dose of ionizing X-ray radiation at 20 Gys, and then NF kappa B expression was monitored. The IVDs were then subjected to mechanical testing using dynamic compression, glycosaminoglycan (GAG) quantification, and histological analyses. Results: In the 1-month-old FSUs, the NF kappa B-driven luciferase activity was significantly elevated for 1 day following the exposure to radiation. The 6-month-old FSUs showed increased NF kappa B activity for 3 days, while the 16-month-old FSUs sustained elevated levels of NF kappa B activity throughout the 10-day culture period. All irradiated groups showed significant loss of disc height, GAG content, mechanical function and changes in structure. Ablation of MyD88 blunted the radiation-mediated NF kappa B signaling, and preserved GAG content, and the IVDs' structure and mechanical performance. Conclusions: These results suggest that high-dose radiation affects the IVDs' NF kappa B-dependent inflammatory processes that subsequently lead to functional deterioration. Blocking the transactivation potential of NF kappa B via MyD88 ablation preserved the structure and mechanical function of the FSUs. The long-term effects of radiation on IVD homeostasis should be considered in individuals susceptible to occupational and medical exposure.