TY - JOUR
T1 - The age-dependent effect of high-dose X-ray radiation on NFκB signaling, structure, and mechanical behavior of the intervertebral disc
AU - Liu, Jennifer W.
AU - Piersma, Sytse
AU - Tang, Simon Y.
N1 - Funding Information:
This study received support from the Washington University Musculoskeletal Research Center NIH P30 AR057235, NIH UL1 TR002345, NIH K01 AR069116, NIH R21 AR069804, and NIH R01 AR074441. The authors gratefully acknowledge the technical assistance of Justin Lipner, Ph.D., and Julie Prior of the Molecular Imaging Core and WUSM Optical Radiology Lab.
Funding Information:
This work was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases [K01 AR069116, P30 AR057235, R01 AR074441, R21 AR069804, UL1 TR002345]. This study received support from the Washington University Musculoskeletal Research Center NIH P30 AR057235, NIH UL1 TR002345, NIH K01 AR069116, NIH R21 AR069804, and NIH R01 AR074441. The authors gratefully acknowledge the technical assistance of Justin Lipner, Ph.D., and Julie Prior of the Molecular Imaging Core and WUSM Optical Radiology Lab.
Publisher Copyright:
© 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2020/7/3
Y1 - 2020/7/3
N2 - 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.
AB - 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.
KW - Inflammation
KW - Intervertebral disc
KW - Ionizing radiation
KW - NFκB
KW - degeneration
KW - organ culture
UR - http://www.scopus.com/inward/record.url?scp=85077395113&partnerID=8YFLogxK
U2 - 10.1080/03008207.2019.1703963
DO - 10.1080/03008207.2019.1703963
M3 - Article
C2 - 31875721
AN - SCOPUS:85077395113
VL - 61
SP - 399
EP - 408
JO - Connective Tissue Research
JF - Connective Tissue Research
SN - 0300-8207
IS - 3-4
ER -