TY - JOUR
T1 - Effects of ex vivo ionizing radiation on collagen structure and whole-bone mechanical properties of mouse vertebrae
AU - Pendleton, Megan M.
AU - Emerzian, Shannon R.
AU - Liu, Jennifer
AU - Tang, Simon Y.
AU - O'Connell, Grace D.
AU - Alwood, Joshua S.
AU - Keaveny, Tony M.
N1 - Funding Information:
This study was supported by NASA Science & Technology Research Fellowship NNX14AM56H (MMP), National Science Foundation Graduate Research Fellowship Program # 1752814 (SRE), a NASA Space Biology PECASE (JSA), and grants from the National Institutes of Health ( K01AR069116 , R21AR069804 , R01AR07444 ) (SYT). This research used resources of the Advanced Light Source, which is a DOE Office of Science User Facility under contract No. DE-AC02-05CH11231. Computational resources were made available through the National Science Foundation via XSEDE, Grant TG-MCA00N019 (TMK). The authors would like to thank Saghi Sadoughi (UCB) for her assistance with finite element modeling, Alfred Li (UCSF) for his micro-CT expertise, Dula Parkinson (LBNL) for his support with the irradiation protocol, and Tamara Alliston (UCSF), Thomas Willet (University of Waterloo), and Elumalai Rangasamy (Agilent Technologies) for their guidance on the biochemical assays.
Funding Information:
This study was supported by NASA Science & Technology Research Fellowship NNX14AM56H (MMP), National Science Foundation Graduate Research Fellowship Program #1752814 (SRE), a NASA Space Biology PECASE (JSA), and grants from the National Institutes of Health (K01AR069116, R21AR069804, R01AR07444) (SYT). This research used resources of the Advanced Light Source, which is a DOE Office of Science User Facility under contract No. DE-AC02-05CH11231. Computational resources were made available through the National Science Foundation via XSEDE, Grant TG-MCA00N019 (TMK). The authors would like to thank Saghi Sadoughi (UCB) for her assistance with finite element modeling, Alfred Li (UCSF) for his micro-CT expertise, Dula Parkinson (LBNL) for his support with the irradiation protocol, and Tamara Alliston (UCSF), Thomas Willet (University of Waterloo), and Elumalai Rangasamy (Agilent Technologies) for their guidance on the biochemical assays.
Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/11
Y1 - 2019/11
N2 - Bone can become brittle when exposed to ionizing radiation across a wide range of clinically relevant doses that span from radiotherapy (accumulative 50 Gy) to sterilization (~35,000 Gy). While irradiation-induced embrittlement has been attributed to changes in the collagen molecular structure, the relative role of collagen fragmentation versus non-enzymatic collagen crosslinking remains unclear. To better understand the effects of radiation on the bone material without cellular activity, we conducted an ex vivo x-ray radiation experiment on excised mouse lumbar vertebrae. Spinal tissue from twenty-week old, female, C57BL/6J mice were randomly assigned to a single x-ray radiation dose of either 0 (control), 50, 1000, 17,000, or 35,000 Gy. Measurements were made for collagen fragmentation, non-enzymatic collagen crosslinking, and both monotonic and cyclic-loading compressive mechanical properties. We found that the group differences for mechanical properties were more consistent with those for collagen fragmentation than for non-enzymatic collagen crosslinking. Monotonic strength at 17,000 and 35,000 Gy was lower than that of the control by 50% and 73% respectively, (p < 0.001) but at 50 and 1000 Gy was not different than the control. Consistent with those trends, collagen fragmentation only occurred at 17,000 and 35,000 Gy. By contrast, non-enzymatic collagen crosslinking was greater than control for all radiation doses (p < 0.001). All results were consistent both for monotonic and cyclic loading conditions. We conclude that the reductions in bone compressive monotonic strength and fatigue life due to ex vivo ionizing radiation are more likely caused by fragmentation of the collagen backbone than any increases in non-enzymatic collagen crosslinks.
AB - Bone can become brittle when exposed to ionizing radiation across a wide range of clinically relevant doses that span from radiotherapy (accumulative 50 Gy) to sterilization (~35,000 Gy). While irradiation-induced embrittlement has been attributed to changes in the collagen molecular structure, the relative role of collagen fragmentation versus non-enzymatic collagen crosslinking remains unclear. To better understand the effects of radiation on the bone material without cellular activity, we conducted an ex vivo x-ray radiation experiment on excised mouse lumbar vertebrae. Spinal tissue from twenty-week old, female, C57BL/6J mice were randomly assigned to a single x-ray radiation dose of either 0 (control), 50, 1000, 17,000, or 35,000 Gy. Measurements were made for collagen fragmentation, non-enzymatic collagen crosslinking, and both monotonic and cyclic-loading compressive mechanical properties. We found that the group differences for mechanical properties were more consistent with those for collagen fragmentation than for non-enzymatic collagen crosslinking. Monotonic strength at 17,000 and 35,000 Gy was lower than that of the control by 50% and 73% respectively, (p < 0.001) but at 50 and 1000 Gy was not different than the control. Consistent with those trends, collagen fragmentation only occurred at 17,000 and 35,000 Gy. By contrast, non-enzymatic collagen crosslinking was greater than control for all radiation doses (p < 0.001). All results were consistent both for monotonic and cyclic loading conditions. We conclude that the reductions in bone compressive monotonic strength and fatigue life due to ex vivo ionizing radiation are more likely caused by fragmentation of the collagen backbone than any increases in non-enzymatic collagen crosslinks.
KW - Bone strength
KW - Bone-graft
KW - Collagen
KW - Fatigue
KW - Ionizing radiation
KW - Sterilization
UR - http://www.scopus.com/inward/record.url?scp=85071571975&partnerID=8YFLogxK
U2 - 10.1016/j.bone.2019.115043
DO - 10.1016/j.bone.2019.115043
M3 - Article
C2 - 31445224
AN - SCOPUS:85071571975
VL - 128
JO - Bone
JF - Bone
SN - 8756-3282
M1 - 115043
ER -