EFFECTS OF ORAL ESTRADIOL THERAPY ON OSTEOCLASTOGENESIS

口服雌二醇治疗对破骨细胞生成的影响

基本信息

  • 批准号:
    7719099
  • 负责人:
  • 金额:
    $ 0.18万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2008
  • 资助国家:
    美国
  • 起止时间:
    2008-04-01 至 2009-03-31
  • 项目状态:
    已结题

项目摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our understanding of the mechanisms by which estrogens regulate bone cells are incomplete. This process is important because estrogen loss by women after menopause and probably in hypogonadal men produces a relatively rapid decrease in bone mass and predisposes susceptible individuals to the development of the disease osteoporosis. This translational project is the result of a collaboration between basic and clinical scientists at the University of Connecticut Health Center (UCHC) whose work focuses on the identification of the mechanisms by which human beings develop the disease osteoporosis. Our specific goal in this pilot project is to examine the differences in cellular and molecular changes that occur in the bone marrow of sex steroid-replete and deficient older men and postmenopausal women in response to estrogen, as preliminary data in mice demonstrates the importance of this hormone. In preliminary work we have found that ovariectomy in mice is rapidly followed by an increase in the ability of bone marrow cells to differentiate into osteoclasts, the cells that mediate bone resorption. This finding suggests that regulates the ability of hematopoietic precursor cells to differentiate into osteoclasts, a process that has not been adequately examined. Since increased rates of bone resorption appear to be the earliest known effects of estrogen withdrawal on the human skeleton, a better understanding of this process may lead to more effective therapies for the treatment of osteoporosis in both men and women. Specific Aim 1:Examine the osteoclastogenic potential of each of these three groups of older men by evaluation of bone marrow aspirates both before and after treatment with Estrogen (E2). Specific Aim 2: Examine parameters of B-lymphocyte lineage development and osteoclast formation in cells from bone marrow including markers of B-lymphocyte lineage development, and the percentage of early and mature B-lymphocytes in the bone marrow before and after E2 treatment. These studies will also evaluate the ability of fractionated (CD19+ and CD19-) bone marrow cells to form osteoclasts-like cells in vitro with and without treatment with receptor activator of NF-kappa B-ligand (RANKL) and monocyte- colony stimulating factor (M-CSF). Specific Aim 3: Examine the expression in the bone marrow of factors known to influence osteoclast formation including messenger ribonucleic acid (RNA) for RANKL, receptor activator of NF-kappa B (RANK), osteoprotegerin (OPG), M-CSF and the M-CSF receptor (c-Fms). We will also measure protein levels of RANK and c-Fms by flow cytometry.
该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金, 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说,它不一定是研究者的机构。 我们对雌激素调节骨细胞机制的理解并不完整。 这个过程很重要,因为绝经后女性和性腺功能减退男性的雌激素流失会导致骨量相对快速减少,并使易感个体容易患上骨质疏松症。 该转化项目是康涅狄格大学健康中心 (UCHC) 基础科学家和临床科学家合作的结果,他们的工作重点是确定人类患上骨质疏松症的机制。 我们在这个试点项目中的具体目标是检查性类固醇充足和缺乏的老年男性和绝经后女性的骨髓中发生的细胞和分子变化对雌激素的反应差异,因为小鼠的初步数据证明了这种激素的重要性。 在初步工作中,我们发现小鼠卵巢切除术后,骨髓细胞分化为破骨细胞(介导骨吸收的细胞)的能力迅速增强。 这一发现表明调节造血前体细胞分化为破骨细胞的能力,这一过程尚未得到充分研究。 由于骨吸收率增加似乎是雌激素撤退对人体骨骼最早已知的影响,因此更好地了解这一过程可能会导致治疗男性和女性骨质疏松症的更有效疗法。 具体目标 1:通过评估雌激素 (E2) 治疗前后的骨髓抽吸物,检查这三组老年男性的破骨潜力。 具体目标 2:检查骨髓细胞中 B 淋巴细胞谱系发育和破骨细胞形成的参数,包括 B 淋巴细胞谱系发育的标志物,以及 E2 治疗前后骨髓中早期和成熟 B 淋巴细胞的百分比。 这些研究还将评估分离的(CD19+和CD19-)骨髓细胞在体外形成破骨细胞样细胞的能力,无论是否经过NF-κB-配体受体激活剂(RANKL)和单核细胞集落刺激因子(M-CSF)处理。 具体目标 3:检查骨髓中已知影响破骨细胞形成的因子的表达,包括 RANKL 的信使核糖核酸 (RNA)、NF-κ B 受体激活剂 (RANK)、骨保护素 (OPG)、M-CSF 和 M-CSF 受体 (c-Fms)。我们还将通过流式细胞术测量 RANK 和 c-Fms 的蛋白质水平。

项目成果

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PAMELA TAXEL其他文献

PAMELA TAXEL的其他文献

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{{ truncateString('PAMELA TAXEL', 18)}}的其他基金

CLINICAL TRIAL: THE EFFECT OF RISEDRONATE ON BONE TURNOVER AND BONE MASS IN OLDE
临床试验:利塞膦酸盐对老年骨转换和骨量的影响
  • 批准号:
    7719094
  • 财政年份:
    2008
  • 资助金额:
    $ 0.18万
  • 项目类别:
EFFECT OF LETROZOLE ON BONE MARKERS AND BLOOD PRESSURE
来曲唑对骨标志物和血压的影响
  • 批准号:
    7607617
  • 财政年份:
    2007
  • 资助金额:
    $ 0.18万
  • 项目类别:
EFFECTS OF ORAL ESTRADIOL THERAPY ON OSTEOCLASTOGENESIS
口服雌二醇治疗对破骨细胞生成的影响
  • 批准号:
    7607593
  • 财政年份:
    2007
  • 资助金额:
    $ 0.18万
  • 项目类别:
ACUTE ESTROGEN IN WOMEN
女性的急性雌激素
  • 批准号:
    7607588
  • 财政年份:
    2007
  • 资助金额:
    $ 0.18万
  • 项目类别:
THE EFFECT OF RISEDRONATE ON BONE TURNOVER AND BONE MASS IN OLDER MEN RECEIVING
利塞膦酸钠对老年男性骨转换和骨量的影响
  • 批准号:
    7607585
  • 财政年份:
    2007
  • 资助金额:
    $ 0.18万
  • 项目类别:
ALENDRONATE
阿仑膦酸钠
  • 批准号:
    7377307
  • 财政年份:
    2006
  • 资助金额:
    $ 0.18万
  • 项目类别:
ACUTE ESTROGEN IN WOMEN
女性的急性雌激素
  • 批准号:
    7377314
  • 财政年份:
    2006
  • 资助金额:
    $ 0.18万
  • 项目类别:
THE EFFECT OF RISEDRONATE ON BONE TURNOVER AND BONE MASS IN OLDER MEN RECEIVING
利塞膦酸钠对老年男性骨转换和骨量的影响
  • 批准号:
    7377311
  • 财政年份:
    2006
  • 资助金额:
    $ 0.18万
  • 项目类别:
EFFECT OF LETROZOLE ON BONE MARKERS AND BLOOD PRESSURE
来曲唑对骨标志物和血压的影响
  • 批准号:
    7377352
  • 财政年份:
    2006
  • 资助金额:
    $ 0.18万
  • 项目类别:
EFFECTS OF ORAL ESTRADIOL THERAPY ON OSTEOCLASTOGENESIS
口服雌二醇治疗对破骨细胞生成的影响
  • 批准号:
    7203915
  • 财政年份:
    2005
  • 资助金额:
    $ 0.18万
  • 项目类别:
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