title: Devastation of adult stem cell pools by irradiation precedes collapse of trabecular bone quality and quantity.
abstract: Stem cell depletion and compromised bone marrow resulting from radiation exposure fosters long-term deterioration of numerous physiologic systems, with the degradation of the skeletal system ultimately increasing the risk of fractures. To study the interrelationship of damaged bone marrow cell populations with trabecular microarchitecture, 8- and 16-week-old C57BL/6 male mice were sublethally irradiated with 5 Gy of (137)Cs γ-rays, and adult stem cells residing in the bone marrow, as well as bone quantity and quality, were evaluated in the proximal tibia after 2 days, 10 days, and 8 weeks compared with age-matched controls. Total extracted bone marrow cells in the irradiated 8-week, young adult mice, including the hematopoietic cell niches, collapsed by 65% ± 11% after 2 days, remaining at those levels through 10 days, only recovering to age-matched control levels by 8 weeks. As early as 10 days, double-labeled surface was undetectable in the irradiated group, paralleled by a 41% ± 12% and 33% ± 4% decline in bone volume fraction (BV/TV) and trabecular number (Tb.N), respectively, and a 50% ± 10% increase in trabecular separation (Tb.Sp) compared with the age-matched controls, a compromised structure that persisted to 8 weeks postirradiation. Although the overall collapse of the bone marrow population and devastation of bone quality was similar between the "young adult" and "mature" mice, the impact of irradiation--and the speed of recovery--on specific hematopoietic subpopulations was dependent on age, with the older animals slower to restore key progenitor populations. These data indicate that, independent of animal age, complications arising from irradiation extend beyond the collapse of the stem cell population and extend toward damage to key organ systems. It is reasonable to presume that accelerating the recovery of these stem cell pools will enable the prompt repair of the skeletal system and ultimately reduce the susceptibility to fractures.
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY 11794-2580, USA.
authors.forename: Danielle E
authors.initials: DE
authors.lastname: Green
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Adler
authors.forename: Meilin E
authors.initials: ME
authors.lastname: Chan
authors.forename: Clinton T
authors.initials: CT
authors.lastname: Rubin
mesh_terms: D053687:Adult Stem Cells / Q000473:pathology* / Q000528:radiation effects*; D000375:Aging / Q000528:radiation effects; D000818:Animals; D001853:Bone Marrow / Q000473:pathology / Q000528:radiation effects; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000473:pathology* / Q000528:radiation effects*; D005720:Gamma Rays; D006412:Hematopoietic Stem Cells / Q000473:pathology / Q000528:radiation effects; D007962:Leukocytes / Q000473:pathology / Q000528:radiation effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000528:radiation effects; D010641:Phenotype; D058985:Side-Population Cells / Q000473:pathology / Q000528:radiation effects; D015431:Weight Loss / Q000528:radiation effects; D055114:X-Ray Microtomography