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Title: Dose- and Ion-Dependent Effects in the Oxidative Stress Response to Space-Like Radiation Exposure in the Skeletal System

Abstract

Space radiation may pose a risk to skeletal health during subsequent aging. Irradiation acutely stimulates bone remodeling in mice, although the long-term influence of space radiation on bone-forming potential (osteoblastogenesis) and possible adaptive mechanisms are not well understood. We hypothesized that ionizing radiation impairs osteoblastogenesis in an ion-type specific manner, with low doses capable of modulating expression of redox-related genes. 16-weeks old, male, C57BL6/J mice were exposed to low linear-energy-transfer (LET) protons (150 MeV/n) or high-LET 56Fe ions (600 MeV/n) using either low (5 or 10 cGy) or high (50 or 200 cGy) doses at NASA’s Space Radiation Lab. Five weeks or one year after irradiation, tissues were harvested and analyzed by microcomputed tomography for cancellous microarchitecture and cortical geometry. Marrow-derived, adherent cells were grown under osteoblastogenic culture conditions. Cell lysates were analyzed by RT-PCR during the proliferative or mineralizing phase of growth, and differentiation was analyzed by imaging mineralized nodules. As expected, a high dose (200 cGy), but not lower doses, of either 56Fe or protons caused a loss of cancellous bone volume/total volume. Marrow cells produced mineralized nodules ex vivo regardless of radiation type or dose; 56Fe (200 cGy) inhibited osteoblastogenesis by more than 90% (5 weeks andmore » 1 year post-IR). After 5 weeks, irradiation (protons or 56Fe) caused few changes in gene expression levels during osteoblastogenesis, although a high dose 56Fe (200 cGy) increased Catalase and Gadd45. The addition of exogenous superoxide dismutase (SOD) protected marrow-derived osteoprogenitors from the damaging effects of exposure to low-LET (137Cs γ) when irradiated in vitro, but had limited protective effects on high-LET 56Fe-exposed cells. In sum, either protons or 56Fe at a relatively high dose (200 cGy) caused persistent bone loss, whereas only high-LET 56Fe increased redox-related gene expression, albeit to a limited extent, and inhibited osteoblastogenesis. Doses below 50 cGy did not elicit widespread responses in any parameter measured. We conclude that high-LET irradiation at 200 cGy impaired osteoblastogenesis and regulated steady-state gene expression of select redox-related genes during osteoblastogenesis, which may contribute to persistent bone loss.« less

Authors:
 [1];  [1];  [1];  [1];  [1];  [1];  [2];  [1]
  1. NASA Ames Research Center (ARC), Moffett Field, Mountain View, CA (United States). Bone and Signaling Lab., Space BioSciences Division
  2. NASA Ames Research Center (ARC), Moffett Field, Mountain View, CA (United States). Bone and Signaling Lab., Space BioSciences Division; Wyle Lab., Moffett Field, CA (United States)
Publication Date:
Research Org.:
NASA Ames Research Center (ARC), Moffett Field, Mountain View, CA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1545337
Grant/Contract Number:  
SC0001507
Resource Type:
Accepted Manuscript
Journal Name:
International Journal of Molecular Sciences (Online)
Additional Journal Information:
Journal Name: International Journal of Molecular Sciences (Online); Journal Volume: 18; Journal Issue: 10; Journal ID: ISSN 1422-0067
Publisher:
MDPI
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; 63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.

Citation Formats

Alwood, Joshua, Tran, Luan, Schreurs, Ann-Sofie, Shirazi-Fard, Yasaman, Kumar, Akhilesh, Hilton, Diane, Tahimic, Candice, and Globus, Ruth. Dose- and Ion-Dependent Effects in the Oxidative Stress Response to Space-Like Radiation Exposure in the Skeletal System. United States: N. p., 2017. Web. doi:10.3390/ijms18102117.
Alwood, Joshua, Tran, Luan, Schreurs, Ann-Sofie, Shirazi-Fard, Yasaman, Kumar, Akhilesh, Hilton, Diane, Tahimic, Candice, & Globus, Ruth. Dose- and Ion-Dependent Effects in the Oxidative Stress Response to Space-Like Radiation Exposure in the Skeletal System. United States. doi:10.3390/ijms18102117.
Alwood, Joshua, Tran, Luan, Schreurs, Ann-Sofie, Shirazi-Fard, Yasaman, Kumar, Akhilesh, Hilton, Diane, Tahimic, Candice, and Globus, Ruth. Tue . "Dose- and Ion-Dependent Effects in the Oxidative Stress Response to Space-Like Radiation Exposure in the Skeletal System". United States. doi:10.3390/ijms18102117. https://www.osti.gov/servlets/purl/1545337.
@article{osti_1545337,
title = {Dose- and Ion-Dependent Effects in the Oxidative Stress Response to Space-Like Radiation Exposure in the Skeletal System},
author = {Alwood, Joshua and Tran, Luan and Schreurs, Ann-Sofie and Shirazi-Fard, Yasaman and Kumar, Akhilesh and Hilton, Diane and Tahimic, Candice and Globus, Ruth},
abstractNote = {Space radiation may pose a risk to skeletal health during subsequent aging. Irradiation acutely stimulates bone remodeling in mice, although the long-term influence of space radiation on bone-forming potential (osteoblastogenesis) and possible adaptive mechanisms are not well understood. We hypothesized that ionizing radiation impairs osteoblastogenesis in an ion-type specific manner, with low doses capable of modulating expression of redox-related genes. 16-weeks old, male, C57BL6/J mice were exposed to low linear-energy-transfer (LET) protons (150 MeV/n) or high-LET 56Fe ions (600 MeV/n) using either low (5 or 10 cGy) or high (50 or 200 cGy) doses at NASA’s Space Radiation Lab. Five weeks or one year after irradiation, tissues were harvested and analyzed by microcomputed tomography for cancellous microarchitecture and cortical geometry. Marrow-derived, adherent cells were grown under osteoblastogenic culture conditions. Cell lysates were analyzed by RT-PCR during the proliferative or mineralizing phase of growth, and differentiation was analyzed by imaging mineralized nodules. As expected, a high dose (200 cGy), but not lower doses, of either 56Fe or protons caused a loss of cancellous bone volume/total volume. Marrow cells produced mineralized nodules ex vivo regardless of radiation type or dose; 56Fe (200 cGy) inhibited osteoblastogenesis by more than 90% (5 weeks and 1 year post-IR). After 5 weeks, irradiation (protons or 56Fe) caused few changes in gene expression levels during osteoblastogenesis, although a high dose 56Fe (200 cGy) increased Catalase and Gadd45. The addition of exogenous superoxide dismutase (SOD) protected marrow-derived osteoprogenitors from the damaging effects of exposure to low-LET (137Cs γ) when irradiated in vitro, but had limited protective effects on high-LET 56Fe-exposed cells. In sum, either protons or 56Fe at a relatively high dose (200 cGy) caused persistent bone loss, whereas only high-LET 56Fe increased redox-related gene expression, albeit to a limited extent, and inhibited osteoblastogenesis. Doses below 50 cGy did not elicit widespread responses in any parameter measured. We conclude that high-LET irradiation at 200 cGy impaired osteoblastogenesis and regulated steady-state gene expression of select redox-related genes during osteoblastogenesis, which may contribute to persistent bone loss.},
doi = {10.3390/ijms18102117},
journal = {International Journal of Molecular Sciences (Online)},
number = 10,
volume = 18,
place = {United States},
year = {2017},
month = {10}
}

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