Study on direct action of estrogen on mature osteoclasts

雌激素对成熟破骨细胞直接作用的研究

基本信息

  • 批准号:
    08672087
  • 负责人:
  • 金额:
    $ 1.41万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
  • 财政年份:
    1996
  • 资助国家:
    日本
  • 起止时间:
    1996 至 1997
  • 项目状态:
    已结题

项目摘要

Estrogen deficiency, cause by either menopause ovariectomy, results in pathological bone loss, which can be prevented by estrogen replacement therapy. Although it is believed that estrogen's main action in preventing bone loss is through inhibition of osteoclastic bone resorption, the precise mechanism of such effect is not clear, largely due to technical difficulties in obtaining purified functional osteoclasts. Throughout this study, we used two unique isolation methods of highly purified mammalian osteoclasts, which were recently developed by us : one is the purification on plastic dished to get a large number of osteoclasts for molecular biological analyzes, and the other is the isolation of osteoclasts in cell suspension for estimation of osteoclastic bone-resorbing activity. In a range of physiological concentrations of estrogen (10^<-12>-10^<-10>M), estrogen inhibited osteoclastic bone resorbing activity. In the same concentration range, estrogen also reduced mRNA levels of cathepsin K,which is abundantly and specifically expressed in osteoclasts, and of carbonic anhydrase II,that is involved in proton production in osteoclasts. Furthermore, estrogen induced osteoclast apoptosis in a dose-and time-dependent manner. ICI1164,384 and tamoxifen, as pure and partial antagonists, respectively, completely and partially blocked the effect of estrogen on both inhibition of osteoclastic bone resorption and induction of osteoclast apoptosis. Finally, we detected the mRNA expression of estrogen reccptor (ERA), but not BRb. Thses data suggest that the protective effects of estrogen against postmenopausal osteoporosis are mediated in part by the direct reduction of key enzymes for osteoclastic bone resorption and the direct induction of osteoclast apoptosis via estrogen receptor-mediated mechanisms.
绝经期卵巢切除术引起的雌激素缺乏会导致病理性骨丢失,这可以通过雌激素替代疗法来预防。虽然人们认为雌激素在防止骨丢失中的主要作用是通过抑制破骨细胞的骨吸收,但这种作用的确切机制尚不清楚,主要是由于获得纯化的功能性破骨细胞的技术困难。在本研究中,我们采用了两种独特的高纯度哺乳动物破骨细胞的分离方法,这是我们最近开发的:一种是塑料碟上纯化,以获得大量的破骨细胞的分子生物学分析,另一种是在细胞悬液中分离破骨细胞,以评估破骨细胞的骨吸收活性。在一定生理浓度的雌激素(10 μ <-12>M-10 μ <-10>M)范围内,雌激素抑制骨细胞的骨吸收活性。在相同的浓度范围内,雌激素也降低了组织蛋白酶K的mRNA水平,这是大量和特异性地表达在破骨细胞中,和碳酸酐酶II,这是参与在破骨细胞中的质子生产。雌激素诱导破骨细胞凋亡呈剂量和时间依赖性。ICI 1164、384和他莫昔芬作为纯拮抗剂和部分拮抗剂,分别完全和部分阻断雌激素抑制骨细胞骨吸收和诱导破骨细胞凋亡的作用。最后检测雌激素受体(ERA)mRNA的表达,未检测到BRb的表达。这些数据表明,雌激素对绝经后骨质疏松症的保护作用部分是通过直接减少骨细胞骨吸收的关键酶和通过雌激素受体介导的机制直接诱导破骨细胞凋亡来介导的。

项目成果

期刊论文数量(7)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Kameda,T., et al.: "Estrogen inhibits bone resorption by directly inducing apoptosis of the bone-resorbing osteoclasts." J.Exp.Med.186. 489-495 (1997)
Kameda,T. 等人:“雌激素通过直接诱导骨吸收破骨细胞凋亡来抑制骨吸收。”
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Mano,H.,et al: "Mammalian mature osteoclasts as estrogen target cells" Biochem.Biophys.Res.Commun.223. 637-642 (1996)
Mano,H.等人:“哺乳动物成熟破骨细胞作为雌激素靶细胞”Biochem.Biophys.Res.Commun.223。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Kameda, T., et al.: "Estrogen inhibits bone resorption by directly inducing apoptosis of the bone resorbing osteoclasts." J.Exp.Med.186. 489-495 (1997)
Kameda, T. 等人:“雌激素通过直接诱导骨吸收破骨细胞凋亡来抑制骨吸收。”
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Mano, H., et al.: "Mammalian mature osteoclasts as estrogen target cells." Biochem.Biophysic.Res.Commun.223. 637-642 (1996)
Mano, H. 等人:“哺乳动物成熟破骨细胞作为雌激素靶细胞。”
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Kameda, T., et al.: "Estrogen inhibits bone resorption by directly inducing apoptosis of the bone-resorbing osteoclasts." J.Exp.Med.186. 489-495 (1997)
Kameda, T. 等人:“雌激素通过直接诱导骨吸收破骨细胞凋亡来抑制骨吸收。”
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
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HAKEDA Yoshiyuki其他文献

HAKEDA Yoshiyuki的其他文献

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{{ truncateString('HAKEDA Yoshiyuki', 18)}}的其他基金

Elucidation of Involvement of LOX-1 in inflammatory bone destruction and the molecular mechanism for the LOX-1 actions, and an approach to develop the new drug for bone diseases.
阐明LOX-1参与炎症性骨破坏及其作用的分子机制,以及开发骨病新药的方法。
  • 批准号:
    16H05505
  • 财政年份:
    2016
  • 资助金额:
    $ 1.41万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Trial study for the establishment of the new therapeutical method for periodontal disease that targets oxidation LDL receptor LOX-1.
建立针对氧化LDL受体LOX-1的牙周病新治疗方法的试验研究。
  • 批准号:
    26670895
  • 财政年份:
    2014
  • 资助金额:
    $ 1.41万
  • 项目类别:
    Grant-in-Aid for Challenging Exploratory Research
The elucidation of the role of lipid in bone resorption of inflammatory bone diseases; in particular, the exploration of the role of LOX-1 as an oxidized LDL receptor
阐明脂质在炎症性骨病骨吸收中的作用;
  • 批准号:
    25293376
  • 财政年份:
    2013
  • 资助金额:
    $ 1.41万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
DEPENDENCY OF OSTEOCLAST DIFFERENTIATION ON EXOGENOUS CHOLESTEROL AND ROLE OF CAVEOLIN-1 IN OSTEOCLASTOGENESIS
破骨细胞分化对外源胆固醇的依赖性以及 CAVEOLIN-1 在破骨细胞生成中的作用
  • 批准号:
    21592341
  • 财政年份:
    2009
  • 资助金额:
    $ 1.41万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Elucidation on roles of caveolae/lipid raft on osteoclast differentiation and bone resorption and on intracellular trafficking of caveolin-1
阐明小窝/脂筏对破骨细胞分化和骨吸收以及小窝蛋白-1 细胞内运输的作用
  • 批准号:
    19592130
  • 财政年份:
    2007
  • 资助金额:
    $ 1.41万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Investigation of action of shear stress, which is produced by Mechanical loading applied to the skeleton, on osteodast formation and bone-resorbing activity
研究由施加到骨骼的机械载荷产生的剪切应力对破骨细胞形成和骨吸收活性的作用
  • 批准号:
    17591922
  • 财政年份:
    2005
  • 资助金额:
    $ 1.41万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Elucidation of role of beta ig-3 derived from osteoclasts in bone resorption and formation
阐明破骨细胞衍生的 β ig-3 在骨吸收和形成中的作用
  • 批准号:
    15591946
  • 财政年份:
    2003
  • 资助金额:
    $ 1.41万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Elucidation of regulatory mechanism of osteoclast differentiation and function by extracellular calcium and phosphorus.
阐明细胞外钙和磷对破骨细胞分化和功能的调节机制。
  • 批准号:
    12671780
  • 财政年份:
    2000
  • 资助金额:
    $ 1.41万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Analysis of osteoclast-specificmembrane-bound proteins that are expressed during osteoclast differentiation
破骨细胞分化过程中表达的破骨细胞特异性膜结合蛋白的分析
  • 批准号:
    06671825
  • 财政年份:
    1994
  • 资助金额:
    $ 1.41万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)

相似海外基金

A new model for spatio-temporal coupling of bone formation and bone resorption governed by osteoclasts
破骨细胞控制的骨形成和骨吸收时空耦合的新模型
  • 批准号:
    10905262
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A new model for spatio-temporal coupling of bone formation and bone resorption governed by osteoclasts
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    10082528
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    2020
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    $ 1.41万
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The Myokine Irisin Modulates Bone Resorption via Stimulation of Osteoclastogenesis
肌动素鸢尾素通过刺激破骨细胞生成调节骨吸收
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  • 财政年份:
    2020
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A new model for spatio-temporal coupling of bone formation and bone resorption governed by osteoclasts
破骨细胞控制的骨形成和骨吸收时空耦合的新模型
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    10249332
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雌激素及雌激素靶因子调控破骨细胞凋亡和骨吸收的机制
  • 批准号:
    15K11010
  • 财政年份:
    2015
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    $ 1.41万
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    Grant-in-Aid for Scientific Research (C)
Osteocyte Apoptosis and Regulation of Bone Resorption with Aging
骨细胞凋亡和骨吸收随衰老的调节
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    9212771
  • 财政年份:
    2015
  • 资助金额:
    $ 1.41万
  • 项目类别:
Osteocyte apoptosis and regulation of bone resorption with aging
衰老过程中骨细胞凋亡和骨吸收的调节
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    9308117
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Runx1 Control of Bone Resorption during Fracture Repair
Runx1 骨折修复过程中骨吸收的控制
  • 批准号:
    8692536
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    $ 1.41万
  • 项目类别:
Runx1 Control of Bone Resorption during Fracture Repair
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    9071289
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