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 NFκB-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 NFκB 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 NFκB-driven luciferase activity was significantly elevated for 1 day following the exposure to radiation. The 6-month-old FSUs showed increased NFκB activity for 3 days, while the 16-month-old FSUs sustained elevated levels of NFκB 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 NFκB signaling, and preserved GAG content, and the IVDs’ structure and mechanical performance.

Conclusions: These results suggest that high-dose radiation affects the IVDs’ NFκB-dependent inflammatory processes that subsequently lead to functional deterioration. Blocking the transactivation potential of NFκB 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.

目的：电离辐射会损害组织并在多个器官系统中引起炎症反应。我们研究了高剂量 X 射线辐射对椎间盘 (IVD) 分子炎症和机械功能的影响。

方法：包含从 1 个月、6 个月和 16 个月大的 NFκB-荧光素酶报告小鼠和 6 个月大的骨髓分化因子 88 ( MyD88 ) 中提取的椎骨-IVDs-椎骨结构的功能性脊柱单元 (FSU) ) -null 小鼠。在培养预处理期后，对 FSU 进行 20 Gys 的单剂量电离 X 射线辐射，然后监测 NFκB 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：在 1 个月大的 FSU 中，NFκB 驱动的荧光素酶活性在暴露于辐射后 1 天内显着升高。6 个月大的 FSU 在 3 天内表现出 NFκB 活性增加，而 16 个月大的 FSU 在整个 10 天的培养期间都保持较高水平的 NFκB 活性。所有受照射组均显示出椎间盘高度、GAG 含量、机械功能和结构变化的显着损失。MyD88的消融减弱了辐射介导的 NFκB 信号，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，高剂量辐射会影响 IVD 的 NFκB 依赖性炎症过程，随后导致功能恶化。通过MyD88消融阻断 NFκB 的反式激活电位，保留了 FSU 的结构和机械功能。对于易受职业和医疗照射影响的个体，应考虑辐射对 IVD 稳态的长期影响。