title: Bone marrow stem cell dysfunction in radiation-induced abscopal bone loss.
abstract: BACKGROUND
  Bone-related complications are commonly reported in cancer patients receiving radiotherapy and are collectively referred to as the abscopal effect of irradiation, the mechanism of which remains poorly understood. When patients receive targeted radiotherapy to a tumor, the local skeleton is exposed to radiation, particularly within the bone marrow. We therefore investigated the hypothesis that single bone irradiation can induce deterioration of the skeleton outside the radiation field and is mediated by the bone marrow.
  
  
  METHODS
  Using 4-month-old male Sprague-Dawley rats, the effects of irradiation (20 Gy, right distal femur and proximal tibia) on bone quality, microarchitecture and bone marrow, were evaluated prospectively by microcomputed tomography, histomorphometry, real-time polymerase chain reaction, and Western blot analysis.
  
  
  RESULTS
  At 12 weeks post-irradiation, bone loss of the non-irradiated bone was induced and marrow adiposity was increased. Expression of runt-related transcription factor-2 by bone mesenchymal stem cells (BMSCs) decreased after irradiation by 88.0 % (P < 0.01) at the contralateral and 82.3 % (P < 0.01) at the irradiation site 2 weeks post-irradiation and decreased by 94.5 % (P < 0.001) at the contralateral and 44.1 % (P < 0.05) at the irradiation site 12 weeks post-irradiation. Interestingly, peroxisome proliferator-activated receptor gamma expression decreased by 61.8 % (P < 0.05) at the contralateral and by 48.3 % (P < 0.05) at the irradiation site 2 weeks post-irradiation but increased by 9-fold at the contralateral (P < 0.001) and by 13-fold (P < 0.001) at the irradiation site 12 weeks post-irradiation.
  
  
  CONCLUSIONS
  These data highlight that radiation-induced bone complications are partly BMSC-mediated, with important implications for bone health maintenance in patients receiving radiotherapy.
authors.affiliation: Department of Radiation Biology, Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Rd. Building 1, Room 407, Shanghai, 200032, China. 08211433@fudan.edu.cn.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Zou
authors.affiliation: Department of Osteoporosis, Hua Dong Hospital Affiliated to Fudan University, Shanghai, China. hong-weibaby@126.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Hong
authors.affiliation: Department of Radiation Biology, Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Rd. Building 1, Room 407, Shanghai, 200032, China. my-guoguo@citiz.net.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Radiation Biology, Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Rd. Building 1, Room 407, Shanghai, 200032, China. 1021114000@fudan.edu.cn.
authors.forename: Qiaoling
authors.initials: Q
authors.lastname: Ding
authors.affiliation: Department of Radiation Biology, Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Rd. Building 1, Room 407, Shanghai, 200032, China. wangjf@sina.com.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Radiation Biology, Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Rd. Building 1, Room 407, Shanghai, 200032, China. jinwf@shmu.edu.cn.
authors.forename: Weifang
authors.initials: W
authors.lastname: Jin
authors.affiliation: Department of Radiation Biology, Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Rd. Building 1, Room 407, Shanghai, 200032, China. jjgao@shmu.edu.cn.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Radiation Biology, Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Rd. Building 1, Room 407, Shanghai, 200032, China. guoqiangh@fudan.edu.cn.
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Hua
authors.affiliation: Department of Radiation Biology, Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Rd. Building 1, Room 407, Shanghai, 200032, China. xiaoyaxu@fudan.edu.cn.
authors.forename: Xiaoya
authors.initials: X
authors.lastname: Xu
mesh_terms: D017667:Adipocytes / Q000502:physiology / Q000528:radiation effects; D000818:Animals; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000528:radiation effects; D001851:Bone Diseases, Metabolic / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D001854:Bone Marrow Cells / Q000502:physiology / Q000528:radiation effects*; D016723:Bone Remodeling / Q000502:physiology / Q000528:radiation effects; D002454:Cell Differentiation / Q000528:radiation effects; D002478:Cells, Cultured; D008297:Male; D059630:Mesenchymal Stem Cells / Q000502:physiology / Q000528:radiation effects*; D010006:Osteoblasts / Q000502:physiology; D010012:Osteogenesis / Q000528:radiation effects; D011832:Radiation Injuries / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D017207:Rats, Sprague-Dawley; D055114:X-Ray Microtomography / Q000379:methods
chemical_list: D015415:Biomarkers