title: The influence of therapeutic radiation on the patterns of bone marrow in ovary-intact and ovariectomized mice.
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.
  
  
  RESULTS
  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
  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.
authors.affiliation: Department of Therapeutic Radiology, Medical School, University of Minnesota, Minneapolis, Minnesota, United States of America. huixx019@umn.edu
authors.forename: Susanta K
authors.initials: SK
authors.lastname: Hui
authors.forename: Leslie
authors.initials: L
authors.lastname: Sharkey
authors.forename: Louis S
authors.initials: LS
authors.lastname: Kidder
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Greg
authors.initials: G
authors.lastname: Fairchild
authors.forename: Kayti
authors.initials: K
authors.lastname: Coghill
authors.forename: Cory J
authors.initials: CJ
authors.lastname: Xian
authors.forename: Douglas
authors.initials: D
authors.lastname: Yee
mesh_terms: D050156:Adipogenesis / Q000528:radiation effects; D000818:Animals; D001853:Bone Marrow / Q000473:pathology / Q000528:radiation effects*; D001842:Bone and Bones / Q000473:pathology / Q000528:radiation effects; D002452:Cell Count; D041905:Erythroid Cells / Q000473:pathology / Q000528:radiation effects; D005260:Female; D005355:Fibrosis; D006410:Hematopoiesis / Q000528:radiation effects; D016018:Least-Squares Analysis; D008533:Megakaryocytes / Q000473:pathology / Q000528:radiation effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D022423:Myeloid Cells / Q000473:pathology / Q000528:radiation effects; D009929:Organ Size / Q000528:radiation effects; D010052:Ovariectomy; D010053:Ovary / Q000473:pathology / Q000528:radiation effects*; D011839:Radiation, Ionizing