title: Irradiation induces bone injury by damaging bone marrow microenvironment for stem cells.
abstract: Radiation therapy can result in bone injury with the development of fractures and often can lead to delayed and nonunion of bone. There is no prevention or treatment for irradiation-induced bone injury. We irradiated the distal half of the mouse left femur to study the mechanism of irradiation-induced bone injury and found that no mesenchymal stem cells (MSCs) were detected in irradiated distal femora or nonirradiated proximal femora. The MSCs in the circulation doubled at 1 week and increased fourfold after 4 wk of irradiation. The number of MSCs in the proximal femur quickly recovered, but no recovery was observed in the distal femur. The levels of free radicals were increased threefold at 1 wk and remained at this high level for 4 wk in distal femora, whereas the levels were increased at 1 wk and returned to the basal level at 4 wk in nonirradiated proximal femur. Free radicals diffuse ipsilaterally to the proximal femur through bone medullary canal. The blood vessels in the distal femora were destroyed in angiographic images, but not in the proximal femora. The osteoclasts and osteoblasts were decreased in the distal femora after irradiation, but no changes were observed in the proximal femora. The total bone volumes were not affected in proximal and distal femora. Our data indicate that irradiation produces free radicals that adversely affect the survival of MSCs in both distal and proximal femora. Irradiation injury to the vasculatures and the microenvironment affect the niches for stem cells during the recovery period.
authors.affiliation: Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Xu
authors.initials: X
authors.lastname: Cao
authors.forename: Xiangwei
authors.initials: X
authors.lastname: Wu
authors.forename: Deborah
authors.initials: D
authors.lastname: Frassica
authors.forename: Bing
authors.initials: B
authors.lastname: Yu
authors.forename: Lijuan
authors.initials: L
authors.lastname: Pang
authors.forename: Lingling
authors.initials: L
authors.lastname: Xian
authors.forename: Mei
authors.initials: M
authors.lastname: Wan
authors.forename: Weiqi
authors.initials: W
authors.lastname: Lei
authors.forename: Michael
authors.initials: M
authors.lastname: Armour
authors.forename: Erik
authors.initials: E
authors.lastname: Tryggestad
authors.forename: John
authors.initials: J
authors.lastname: Wong
authors.forename: Chun Yi
authors.initials: CY
authors.lastname: Wen
authors.forename: William Weijia
authors.initials: WW
authors.lastname: Lu
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Frassica
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D001808:Blood Vessels / Q000473:pathology / Q000528:radiation effects; D001853:Bone Marrow / Q000473:pathology / Q000528:radiation effects*; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D003114:Colony-Forming Units Assay; D005269:Femur / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D005347:Fibroblasts / Q000473:pathology / Q000528:radiation effects; D005609:Free Radicals / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000473:pathology / Q000528:radiation effects; D011833:Radiation Injuries, Experimental / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D000950:Antigens, Ly; D005609:Free Radicals; D019012:Integrin beta1; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D017392:Thiobarbituric Acid Reactive Substances; D017493:Leukocyte Common Antigens; C516770:Ptprc protein, mouse