Bone marrow stem cell dysfunction in radiation-induced abscopal bone loss
- PDF / 2,009,259 Bytes
- 10 Pages / 595.276 x 790.866 pts Page_size
- 5 Downloads / 207 Views
RESEARCH ARTICLE
Open Access
Bone marrow stem cell dysfunction in radiation-induced abscopal bone loss Qiong Zou1, Wei Hong2, Yi Zhou1, Qiaoling Ding1, Jinfeng Wang1, Weifang Jin1, Jianjun Gao1, Guoqiang Hua1 and Xiaoya Xu1*
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. Keywords: Irradiation, Abscopal effect, Marrow adiposity, BMSCs, Runx2, PPAR γ
Background Following the discovery of X-rays by the German physicist Wilhelm Conrad Roentgen, radiation was used to treat cancer patients and has since been proven as an effective treatment [1, 2]. However, the side effects of irradiation come at the expense of normal tissue injury, especially with the widespread use of radiotherapy in cancer patients [3, 4]. Local irradiation is known to be a common treatment for malignancies such as prostate, pancreatic, cervical, rectal, and endometrial cancers, and with direct irradiation exposure to the bone being inevitable, adverse effects of irradiation on the skeleton are common [5–8]. * Correspondence: [email protected] 1 Department of Radiation Biology, Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Rd. Building 1, Room 407, Shanghai 200032, China Full list of author information is available at the end
Data Loading...
