Jennifer W Liu1,2, Sytse Piersma3, Simon Y Tang1,2,4. 1. Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, USA. 2. Department of Orthopaedic Surgery, Washington University in St. Louis, St. Louis, MO, USA. 3. Division of Rheumatology, Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA. 4. Department of Materials Science and Mechanical Engineering, Washington University in St. Louis, St. Louis, MO, USA.
Abstract
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.
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.
Entities:
Keywords:
Inflammation; Intervertebral disc; Ionizing radiation; NFκB; degeneration; organ culture
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