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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Irradiation induces bone injury by damaging bone marrow microenvironment for stem cells
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Irradiation induces bone injury by damaging bone marrow microenvironment for stem cells

机译:辐射通过破坏干细胞的骨髓微环境而引起骨损伤

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摘要

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.
机译:放射治疗可导致骨折并发展为骨伤,并经常导致骨延迟和骨不连。没有针对辐射诱发的骨损伤的预防或治疗方法。我们辐照了小鼠左股骨的远端,研究了辐照引起的骨损伤的机制,发现辐照的股骨远端或未辐照的股骨近端均未检测到间充质干细胞(MSCs)。照射后1周,循环中的MSC数量增加了一倍,并增加了四倍。股骨近端的MSC数量迅速恢复,但股骨远端未见恢复。自由基水平在1 wk时增加了三倍,并在股骨远端4 wk处保持这种高水平,而在未照射的股骨近端,其水平在1 wk时增加并恢复到基础水平。自由基通过骨髓管同侧扩散到股骨近端。血管造影图像中破坏了股骨远端的血管,但股骨近端未破坏。放射后股骨远端的破骨细胞和成骨细胞减少,但股骨近端没有观察到变化。股骨近端和远端的总骨量不受影响。我们的数据表明,辐射产生的自由基会对股骨远端和股骨近端MSC的存活产生不利影响。在恢复期,对血管系统和微环境的辐射损伤会影响干细胞的生态位。

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    Departments of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205;

    Departments of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205,Shihezi Medical College, Shihezi University, Shihezi Xinjiang 832002, China;

    Departments of Radiation Oncology and Molecular Radiation Sciences,Johns Hopkins University School of Medicine, Baltimore, MD 21205;

    Departments of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205;

    Departments of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205,Shihezi Medical College, Shihezi University, Shihezi Xinjiang 832002, China;

    Departments of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205;

    Departments of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205;

    Departments of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205;

    Shihezi Medical College, Shihezi University, Shihezi Xinjiang 832002, China;

    Shihezi Medical College, Shihezi University, Shihezi Xinjiang 832002, China;

    Shihezi Medical College, Shihezi University, Shihezi Xinjiang 832002, China;

    Department of Orthopaedics, University of Hong Kong, Hong Kong 999777, China;

    Department of Orthopaedics, University of Hong Kong, Hong Kong 999777, China;

    Departments of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    CFU-fibroblast; repopulation; differentiation; self-renewal; angiography;

    机译:CFU-成纤维细胞再人口;分化;自我更新血管造影;

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