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The influence of therapeutic radiation on the patterns of bone marrow in ovary-intact and ovariectomized mice.

Hui SK, Sharkey L, Kidder LS, Zhang Y, Fairchild G, Coghill K, Xian CJ, Yee D - PLoS ONE (2012)

Bottom Line: Ovariectomy alone did not significantly reduce marrow cellularity in non-irradiated mice (OVX-R vs.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).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Therapeutic Radiology, Medical School, University of Minnesota, Minneapolis, Minnesota, United States of America. huixx019@umn.edu

ABSTRACT

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.

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Ovariectomy influences the relationships between bone volume (BV/TV%), adipogenesis (% marrow fat), and hematopoiesis (% cellularity) at Day 30 with or without 16 Gy radiation to the hind limb in mice.Data of every two measurements are represented as least squares mean values for the group. Panel A: OVX results in a 10 fold reduction in the rate of bone volume loss per unit increase in marrow fat after radiation treatment compared with intact mice. Panel B: OVX blunts the rate of bone volume loss relative to reduced hematopoietic cellularity after radiation compared with intact mice by a factor of 6. Panel C: OVX halves the reduction in hematopoietic cellularity compared with increased marrow fat after radiation treatment compared with intact mice.
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pone-0042668-g004: Ovariectomy influences the relationships between bone volume (BV/TV%), adipogenesis (% marrow fat), and hematopoiesis (% cellularity) at Day 30 with or without 16 Gy radiation to the hind limb in mice.Data of every two measurements are represented as least squares mean values for the group. Panel A: OVX results in a 10 fold reduction in the rate of bone volume loss per unit increase in marrow fat after radiation treatment compared with intact mice. Panel B: OVX blunts the rate of bone volume loss relative to reduced hematopoietic cellularity after radiation compared with intact mice by a factor of 6. Panel C: OVX halves the reduction in hematopoietic cellularity compared with increased marrow fat after radiation treatment compared with intact mice.

Mentions: To help understand the effect of radiation in the presence or absence of ovarian function on the interrelationships between hematopoiesis, adipogenesis, and bone, we calculated radiation-induced changes in each tissue relative to the other two components for ovary-intact and OVX mice based on Figure 4. First we calculated the differences in least squares means of the three tissue components between non-irradiated and irradiated mice in the ovary intact and OVX groups, respectively. Then we calculated the following 3 ratios for each ovarian function group: difference of % BV/TV over that of % marrow fat, difference of % hematopoietic cellularity over that of % marrow fat, and difference of % BV/TV over that of % hematopoietic cellularity. Mathematically these ratios are the slopes of blue and red lines in Figure 4. They indicate the amount of change in one tissue component per unit change in another tissue component.


The influence of therapeutic radiation on the patterns of bone marrow in ovary-intact and ovariectomized mice.

Hui SK, Sharkey L, Kidder LS, Zhang Y, Fairchild G, Coghill K, Xian CJ, Yee D - PLoS ONE (2012)

Ovariectomy influences the relationships between bone volume (BV/TV%), adipogenesis (% marrow fat), and hematopoiesis (% cellularity) at Day 30 with or without 16 Gy radiation to the hind limb in mice.Data of every two measurements are represented as least squares mean values for the group. Panel A: OVX results in a 10 fold reduction in the rate of bone volume loss per unit increase in marrow fat after radiation treatment compared with intact mice. Panel B: OVX blunts the rate of bone volume loss relative to reduced hematopoietic cellularity after radiation compared with intact mice by a factor of 6. Panel C: OVX halves the reduction in hematopoietic cellularity compared with increased marrow fat after radiation treatment compared with intact mice.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3412808&req=5

pone-0042668-g004: Ovariectomy influences the relationships between bone volume (BV/TV%), adipogenesis (% marrow fat), and hematopoiesis (% cellularity) at Day 30 with or without 16 Gy radiation to the hind limb in mice.Data of every two measurements are represented as least squares mean values for the group. Panel A: OVX results in a 10 fold reduction in the rate of bone volume loss per unit increase in marrow fat after radiation treatment compared with intact mice. Panel B: OVX blunts the rate of bone volume loss relative to reduced hematopoietic cellularity after radiation compared with intact mice by a factor of 6. Panel C: OVX halves the reduction in hematopoietic cellularity compared with increased marrow fat after radiation treatment compared with intact mice.
Mentions: To help understand the effect of radiation in the presence or absence of ovarian function on the interrelationships between hematopoiesis, adipogenesis, and bone, we calculated radiation-induced changes in each tissue relative to the other two components for ovary-intact and OVX mice based on Figure 4. First we calculated the differences in least squares means of the three tissue components between non-irradiated and irradiated mice in the ovary intact and OVX groups, respectively. Then we calculated the following 3 ratios for each ovarian function group: difference of % BV/TV over that of % marrow fat, difference of % hematopoietic cellularity over that of % marrow fat, and difference of % BV/TV over that of % hematopoietic cellularity. Mathematically these ratios are the slopes of blue and red lines in Figure 4. They indicate the amount of change in one tissue component per unit change in another tissue component.

Bottom Line: Ovariectomy alone did not significantly reduce marrow cellularity in non-irradiated mice (OVX-R vs.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).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Therapeutic Radiology, Medical School, University of Minnesota, Minneapolis, Minnesota, United States of America. huixx019@umn.edu

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus