全身照射引起间充质干-祖细胞池缩小及成骨潜能改变.docVIP

全身照射引起间充质干/祖细胞池缩小及成骨潜能改变 nbsp;nbsp;nbsp;nbsp;nbsp; 作者：马杰，陈斌，王宏兰，李静，史明霞，李炳宗，胡建立，赵春华 【摘要】nbsp; 　　为了研究辐射对骨髓间充质干细胞（bone marrow mesenchymal stem cells, BMMSC）数量及成骨分化潜能的影响，探讨BMMSC在辐射损伤中的反应及其与照射后造血和骨骼系统长期损伤的关系，用全身照射（total body irradiation, TBI）小鼠模型观察TBI前后不同时间点小鼠骨髓纤维母细胞集落形成单位（colonyforming unitfibroblast, CFUF)的改变及BMMSC细胞周期分布情况；用Von Kossa染色法测定钙盐沉积,实时定量RTPCR检测成骨分化相关基因及成骨转录共刺激因子TAZ (transcriptional coactivator with PDZbinding motif)的表达变化。结果显示：TBI后骨髓CFUF数量明显减少；TBI后3天较多的BMMSC进入细胞周期并且其成骨潜能明显增强，随后细胞周期分布恢复正常，但成骨潜能明显降低，同时伴有TAZ表达改变。结论：TBI能导致小鼠骨髓间充质干/祖细胞池的显著缩小并改变BMMSC的成骨分化潜能，TAZ表达的变化可能在其成骨潜能的改变中发挥一定作用。 【关键词】nbsp; 全身照射；骨髓间充质干细胞；成骨潜能；TAZ 　　 Reduction of Bone Marrow Mesenchymal Stem/Progenitor Cells Pool and Alteration of Their Osteogenesis Potential Caused by Total Body Irradiation nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp; Abstractnbsp;nbsp;nbsp; To investigate the effect of irradiation on the quantity and osteogenesis potential of BMMSCs and to explore the response of them in the irradiation stress and its contribution to longterm effects of radiationinduced bone and hematologic injury, a total body irradiation (TBI) murine model was adopted. The number of CFUF and cell cycle profile of BMMSCs were analyzed at different time points before and after TBI. Osteogenic differentiation was evaluated by Von Kossa staining,nbsp; expressions ofnbsp;nbsp;nbsp; osteogenesisrelated genes and transcriptional coactivator with PDZbinding motif (TAZ)nbsp; were detected by realtime RTPCR. The results showed that the number of CFUF decreased greatly at day 28 after TBI. At day 3 after TBI， more cells entered cell cycle and the osteogenesis potential was greatly enhanced followed by recovery of cell cycle distribution and signifiacant defect in osteoblast differentiation respectively,nbsp; meanwhile the expression of TAZ was changed. It is concluded that TBI results in the reductionnbsp; of bone marrow mesenchymal stem/progenitor cell pool and alters the osteoge