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The Influence of Therapeutic Radiation on the Patterns of Bone Marrow in Ovary-Intact and Ovariectomized Mice
BACKGROUND: The functional components of bone marrow (i.e., the hematopoietic and stromal populations) and the adjacent bone have traditionally been evaluated incompletely as distinct entities rather than the integrated system. We perturbed this system in vivo using a medically relevant radiation mo...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3412808/ https://www.ncbi.nlm.nih.gov/pubmed/22880075 http://dx.doi.org/10.1371/journal.pone.0042668 |
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author | Hui, Susanta K. Sharkey, Leslie Kidder, Louis S. Zhang, Yan Fairchild, Greg Coghill, Kayti Xian, Cory J. Yee, Douglas |
author_facet | Hui, Susanta K. Sharkey, Leslie Kidder, Louis S. Zhang, Yan Fairchild, Greg Coghill, Kayti Xian, Cory J. Yee, Douglas |
author_sort | Hui, Susanta K. |
collection | PubMed |
description | BACKGROUND: The functional components of bone marrow (i.e., the hematopoietic and stromal populations) and the adjacent bone have traditionally been evaluated incompletely as distinct entities rather than the integrated system. We perturbed this system in vivo using a medically relevant radiation model in the presence or absence of ovarian function to understand integrated tissue interaction. METHODOLOGY/PRINCIPAL FINDINGS: Ovary-intact and ovariectomized mice underwent either no radiation or single fractional 16 Gy radiation to the caudal skeleton (I±R, OVX±R). Marrow fat, hematopoietic cellularity, and cancellous bone volume fraction (BV/TV %) were assessed. Ovariectomy alone did not significantly reduce marrow cellularity in non-irradiated mice (OVX−R vs. I−R, p = 0.8445) after 30 days; however it impaired the hematopoietic recovery of marrow following radiation exposure (OVX+R vs. I+R, p = 0.0092). The combination of radiation and OVX dramatically increases marrow fat compared to either factor alone (p = 0.0062). The synergistic effect was also apparent in the reduction of hematopoietic marrow cellularity (p = 0.0661); however it was absent in BV/TV% changes (p = 0.2520). The expected inverse relationship between marrow adiposity vs. hematopoietic cellularity and bone volume was observed. Interestingly compared with OVX mice, intact mice demonstrated double the reduction in hematopoietic cellularity and a tenfold greater degree of bone loss for a given unit of expansion in marrow fat. CONCLUSIONS/SIGNIFICANCE: Ovariectomy prior to delivery of a clinically-relevant focal radiation exposure in mice, exacerbated post-radiation adipose accumulation in the marrow space but blunted bone loss and hematopoietic suppression. In the normally coupled homeostatic relationship between the bone and marrow domains, OVX appears to alter feedback mechanisms. Confirmation of this non-linear phenomenon (presumably due to differential radiosensitivity) and demonstration of the mechanism of action is needed to provide strategies to diminish the effect of radiation on exposed tissues. |
format | Online Article Text |
id | pubmed-3412808 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-34128082012-08-09 The Influence of Therapeutic Radiation on the Patterns of Bone Marrow in Ovary-Intact and Ovariectomized Mice Hui, Susanta K. Sharkey, Leslie Kidder, Louis S. Zhang, Yan Fairchild, Greg Coghill, Kayti Xian, Cory J. Yee, Douglas PLoS One Research Article BACKGROUND: The functional components of bone marrow (i.e., the hematopoietic and stromal populations) and the adjacent bone have traditionally been evaluated incompletely as distinct entities rather than the integrated system. We perturbed this system in vivo using a medically relevant radiation model in the presence or absence of ovarian function to understand integrated tissue interaction. METHODOLOGY/PRINCIPAL FINDINGS: Ovary-intact and ovariectomized mice underwent either no radiation or single fractional 16 Gy radiation to the caudal skeleton (I±R, OVX±R). Marrow fat, hematopoietic cellularity, and cancellous bone volume fraction (BV/TV %) were assessed. Ovariectomy alone did not significantly reduce marrow cellularity in non-irradiated mice (OVX−R vs. I−R, p = 0.8445) after 30 days; however it impaired the hematopoietic recovery of marrow following radiation exposure (OVX+R vs. I+R, p = 0.0092). The combination of radiation and OVX dramatically increases marrow fat compared to either factor alone (p = 0.0062). The synergistic effect was also apparent in the reduction of hematopoietic marrow cellularity (p = 0.0661); however it was absent in BV/TV% changes (p = 0.2520). The expected inverse relationship between marrow adiposity vs. hematopoietic cellularity and bone volume was observed. Interestingly compared with OVX mice, intact mice demonstrated double the reduction in hematopoietic cellularity and a tenfold greater degree of bone loss for a given unit of expansion in marrow fat. CONCLUSIONS/SIGNIFICANCE: Ovariectomy prior to delivery of a clinically-relevant focal radiation exposure in mice, exacerbated post-radiation adipose accumulation in the marrow space but blunted bone loss and hematopoietic suppression. In the normally coupled homeostatic relationship between the bone and marrow domains, OVX appears to alter feedback mechanisms. Confirmation of this non-linear phenomenon (presumably due to differential radiosensitivity) and demonstration of the mechanism of action is needed to provide strategies to diminish the effect of radiation on exposed tissues. Public Library of Science 2012-08-06 /pmc/articles/PMC3412808/ /pubmed/22880075 http://dx.doi.org/10.1371/journal.pone.0042668 Text en © 2012 Hui et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Hui, Susanta K. Sharkey, Leslie Kidder, Louis S. Zhang, Yan Fairchild, Greg Coghill, Kayti Xian, Cory J. Yee, Douglas The Influence of Therapeutic Radiation on the Patterns of Bone Marrow in Ovary-Intact and Ovariectomized Mice |
title | The Influence of Therapeutic Radiation on the Patterns of Bone Marrow in Ovary-Intact and Ovariectomized Mice |
title_full | The Influence of Therapeutic Radiation on the Patterns of Bone Marrow in Ovary-Intact and Ovariectomized Mice |
title_fullStr | The Influence of Therapeutic Radiation on the Patterns of Bone Marrow in Ovary-Intact and Ovariectomized Mice |
title_full_unstemmed | The Influence of Therapeutic Radiation on the Patterns of Bone Marrow in Ovary-Intact and Ovariectomized Mice |
title_short | The Influence of Therapeutic Radiation on the Patterns of Bone Marrow in Ovary-Intact and Ovariectomized Mice |
title_sort | influence of therapeutic radiation on the patterns of bone marrow in ovary-intact and ovariectomized mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3412808/ https://www.ncbi.nlm.nih.gov/pubmed/22880075 http://dx.doi.org/10.1371/journal.pone.0042668 |
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