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首页> 外文期刊>Cell and Tissue Research >Glucocorticoid receptor antagonist and siRNA prevent senescence of human bone marrow mesenchymal stromal cells in vitro
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Glucocorticoid receptor antagonist and siRNA prevent senescence of human bone marrow mesenchymal stromal cells in vitro

机译：糖皮质激素受体拮抗剂和siRNA预防体外人骨髓间充质细胞的衰老

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摘要

We investigate the effects mediated by glucocorticoid (GC) receptor (GR) blockage by using RU486, a GR antagonist and GR short interfering RNA (GR siRNA) on the proliferative and differentiation capabilities of human bone marrow mesenchymal stromal/stem cells (MSCs) and on their senescence and antioxidant levels during extended in vitro culture. Treatment with either RU486 or GR siRNA for a 7-day period significantly increased the proliferation of MSCs and their osteogenic capabilities, as reflected by an increase in alkaline phosphatase (ALP) levels after differentiation. Following 4 weeks of treatment, MSCs improved or maintained their proliferation rates, whereas control MSCs exhibited decreased proliferation. Although all MSCs exhibited reduced osteogenic potential after 4 weeks of in vitro culture, the MSCs treated with GR inhibitors showed higher ALP levels than untreated MSCs on being subjected to osteogenic differentiation. Such treatment also significantly down-regulated the adipogenic capabilities of MSCs. Telomere lengths and the activities of telomerase and superoxide dismutase of MSCs treated with either RU486 or GR siRNA appeared to be higher than those detected in controls. These results demonstrate that the blockage of effects mediated by the GCs normally found in fetal bovine serum might postpone senescence of these cells by up-regulating their antioxidant levels. Our data suggest that the blocking of the effects mediated by GCs might extend the lifespan of endogenous MSCs in patients who have elevated GC levels as a consequence of advancing age or estrogen depletion.
机译：我们通过使用Ru486，GR拮抗剂和GR短干扰RNA（GR siRNA）对人骨髓间充质基质/干细胞（MSCs）的增殖和分化能力进行葡糖皮质激素（GC）受体（GR）阻塞的影响。在延长体外培养过程中衰老和抗氧化水平。用ru486或GR siRNA治疗7天的时间显着增加了MSCs的增殖及其成骨能力，如分化后碱性磷酸酶（ALP）水平的增加。在治疗4周后，MSCs改善或维持其增殖率，而对照MSCs表现出降低降低。尽管所有MSC在体外培养4周后表现出降低的成骨潜力，但是用GR抑制剂处理的MSCs显示出比未处理的MSCs进行成骨分化的未处理的MSCs更高的ALP水平。这种治疗也显着下调了MSCs的脂肪生成能力。用Ru486或GR siRNA处理的MSCs的端粒长度和超氧化物歧化酶的活性似乎高于对照中检测到的MSCs。这些结果表明，通常在胎牛血清中发现的GCS介导的效果堵塞可能通过升高其抗氧化水平来推迟这些细胞的衰老。我们的数据表明，GCS介导的效果的阻断可能延长因推进年龄或雌激素耗尽而升高GC水平的患者内源性MSC的寿命。

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  • 来源
    《Cell and Tissue Research》 |2013年第2期|共10页
  • 作者

    WeiN.; YuY.; JoshiV.; SchmidtT.; QianF.; SalemA.K.; StanfordC.; HongL.;

  • 作者单位

    Dows Institute for Dental Research College of Dentistry University of Iowa 405N DSB 801 Newton;

    Dows Institute for Dental Research College of Dentistry University of Iowa 405N DSB 801 Newton;

    Division of Pharmaceutics College of Pharmacy University of Iowa Iowa City United States;

    Department of Molecular Physiology and Biophysics Carver College of Medicine University of Iowa;

    Dows Institute for Dental Research College of Dentistry University of Iowa 405N DSB 801 Newton;

    Division of Pharmaceutics College of Pharmacy University of Iowa Iowa City United States;

    Dows Institute for Dental Research College of Dentistry University of Iowa 405N DSB 801 Newton;

    Dows Institute for Dental Research College of Dentistry University of Iowa 405N DSB 801 Newton;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 细胞生物学;
  • 关键词

    Glucocorticoid receptor; Human; Mesenchymal stromal cells; RU486; Senescence; siRNA;

    机译：糖皮质激素受体;人;间充质基质细胞;ru486;衰老;siRNA;

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