Analysis of signal transduction of osteoclast differentiation factor (RANKL) in alveolar bone destruction

破骨细胞分化因子(RANKL)在牙槽骨破坏中的信号转导分析

基本信息

  • 批准号:
    13470394
  • 负责人:
  • 金额:
    $ 9.28万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
  • 财政年份:
    2001
  • 资助国家:
    日本
  • 起止时间:
    2001 至 2002
  • 项目状态:
    已结题

项目摘要

Lipopolysaccharide (LPS), the major component of the outer membrane of Gram-negative bacteria, is proposed to be a potent stimulator of bone resorption in inflammatory diseases caused by bacreria. Bacterial lipoprotein/lipopeptides are also pathogen-specific molecular patterns. Recently, toll-like receptor 4 (TLR4) was identified as the signaling receptor for LPS. In addition, TLR6 associate with TLR2, and the complex of TLR6 and TLR2 recognizes diacylated mycoplasmal lipopeptides. The signaling cascade of TLR is believed to be similar to that of IL-1 receptors (IL- 1R), because both TLR and IL-1R use myeloid differentiation factor 88 (MyD88) as a common cytoplasmic signaling molecule. However, accumulating evidence also demonstrates the existence of MyD88-independent pathways, which may explain unique biological responses of individual TLR and IL-1R. Using MyD88-deficient (-/-) mice, we explored the involvement of MyD88-mediated signals in osteoclast formation. LPS, synthetic lipopept … More ide (FSL-1), IL-1a and 1.25(OH)_2D_3 all stimulated osteoclast formation in co-cultures of primary osteoblasts and bone marrow cells obtained from wild-type mice. Osteoprotegerin, a decoy receptor of RANKL, completely inhibited the osteoclast formation in the co-culture. In contrasts, LPS, lipopeptide and IL-1a failed to induce the osteoclast formation in the co-culture of Myd88 (-/-) mice-derived osteoblasts and bone marrow cells, though 1.25(OH)_2D_3 stimulated osteoclast formation even in the MyD88 (-/-) co-culture. RT-PCR analysis showed that primary osteoblasts obtained from both wild type and MyD88 (-/-) mice similarly expressed TLR2, TLR4, TLR6 and IL-1R mRNAs. LPS, lipopeptide and IL-1a stimulated expression of RANKL mRNA within 24 hr in primary osteoblasts obtained from wild-type mice but not in those from MyD88 (-/-) mice. Similarly, LPS and IL-1a stimulated phosphorylation of ERK in wild-type osteoblasts but not MyD88 (-/-) osteoblasts. Hemopoietic cells obtained from MyD88 (-/-) mice and those from wild-type mice similarly differentiated into osteoclasts within 3 days in response to RANKL and M-CSF. These results suggest that the MyD88-mediated signaling pathway is essentially involved in osteoclast formation induced by LPS, lipopeptide and IL-1a through the RANKL expression by osteoblasts. Less
脂多糖(LPS)是革兰氏阴性菌外膜的主要成分,被认为是由细菌引起的炎症性疾病中骨吸收的有效刺激剂。细菌脂蛋白/脂肽也是病原体特异性分子模式。最近,Toll样受体4(TLR 4)被鉴定为LPS的信号受体。另外,TLR 6与TLR 2结合,TLR 6和TLR 2的复合物识别二酰化支原体脂肽。TLR的信号级联被认为与IL-1受体(IL-1 R)的信号级联相似,因为TLR和IL-1 R都使用髓样分化因子88(MyD 88)作为共同的细胞质信号分子。然而,越来越多的证据也表明存在MyD 88非依赖性途径,这可能解释个体TLR和IL-1 R的独特生物学反应。使用MyD 88缺陷(-/-)小鼠,我们探索了MyD 88介导的信号在破骨细胞形成中的参与。LPS,合成脂肽 ...更多信息 IDE(FSL-1)、IL-1a和1.25(OH)_2D_3均能刺激原代成骨细胞和野生型小鼠骨髓细胞共培养中破骨细胞的形成。RANKL的诱骗受体Osteoprotegerin可完全抑制破骨细胞的形成。LPS、脂肽和IL-1a不能诱导Myd 88(-/-)鼠源性成骨细胞和骨髓细胞共培养时破骨细胞的形成,而1.25(OH)_2D_3能促进Myd 88(-/-)鼠源性成骨细胞和骨髓细胞共培养时破骨细胞的形成。RT-PCR分析显示,从野生型和MyD 88(-/-)小鼠获得的原代成骨细胞相似地表达TLR 2、TLR 4、TLR 6和IL-1 R mRNA。LPS、脂肽和IL-1a在24小时内刺激野生型小鼠原代成骨细胞中RANKL mRNA的表达,但在MyD 88(-/-)小鼠中则不然。类似地,LPS和IL-1a刺激野生型成骨细胞中ERK的磷酸化,但不刺激MyD 88(-/-)成骨细胞。从MyD 88(-/-)小鼠和野生型小鼠获得的造血细胞在RANKL和M-CSF的作用下在3天内分化为破骨细胞。这些结果表明,MyD 88介导的信号通路基本上参与了LPS、脂肽和IL-1a通过成骨细胞表达RANKL诱导的破骨细胞形成。少

项目成果

期刊论文数量(68)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Li X et al.: "p38 MAPK is crucially involved in osteoclast differentiation but not in cytokine production, phagocytosis or dendritic cell differentiation of bone marrow macrophages"Endocrinology. (in press). (2003)
Li X等人:“p38 MAPK在破骨细胞分化中至关重要,但不参与骨髓巨噬细胞的细胞因子产生、吞噬作用或树突状细胞分化”内分泌学。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Katagiri T, Takahashi N:, , 2002: "Regulatory mechanisms of osteoblast and osteoclast differentiation"Oral Diseases. (in press). (2002)
Katagiri T, Takahashi N:, , 2002:“成骨细胞和破骨细胞分化的调节机制”口腔疾病。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Suda, N. et al.: "Parathyroid hormone-related protein is required for normal intramembranous bone development."J. Bone Miner. Res.. 16. 2182-2191 (2001)
Suda, N. 等人:“正常的膜内骨发育需要甲状旁腺激素相关蛋白。”J.
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Takahashi N et al.: "Principles of Bone Biology, Second Edition, Volume 1"Academic press. 882 (2002)
高桥N等:《骨生物学原理,第二版,第1卷》学术出版社。
  • DOI:
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  • 期刊:
  • 影响因子:
    0
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UDAGAWA Nobuyuki其他文献

UDAGAWA Nobuyuki的其他文献

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{{ truncateString('UDAGAWA Nobuyuki', 18)}}的其他基金

Exploration of seeds for development of a new drug targeting Bone-Vascular-Spleen axis
骨-血管-脾轴新药种子开发探索
  • 批准号:
    25670793
  • 财政年份:
    2013
  • 资助金额:
    $ 9.28万
  • 项目类别:
    Grant-in-Aid for Challenging Exploratory Research
Analysis of bone remodeling mechanism between osteoblasts and osteoclasts for the alveolar bone regeneration
成骨细胞与破骨细胞促进牙槽骨再生的骨重塑机制分析
  • 批准号:
    24390417
  • 财政年份:
    2012
  • 资助金额:
    $ 9.28万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Basic research on development of new treatment of alveolar bone regeneration
牙槽骨再生新疗法开发的基础研究
  • 批准号:
    21390498
  • 财政年份:
    2009
  • 资助金额:
    $ 9.28万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Elucidation of the regulated mechanism of bone metabolism by osteoclastic transcytosis.
阐明破骨细胞转胞吞作用调节骨代谢的机制。
  • 批准号:
    19390476
  • 财政年份:
    2007
  • 资助金额:
    $ 9.28万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Establishment of periodontitis treatment method by inhibition of RANK-Toll like receptor signal
抑制RANK-Toll样受体信号治疗牙周炎方法的建立
  • 批准号:
    17390497
  • 财政年份:
    2005
  • 资助金额:
    $ 9.28万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Signal transduction of RANK and Toll-like receptor in alveolar bone destruction
RANK和Toll样受体在牙槽骨破坏中的信号转导
  • 批准号:
    15390565
  • 财政年份:
    2003
  • 资助金额:
    $ 9.28万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
The physiological role of osteoclast differentiation factor.
破骨细胞分化因子的生理作用。
  • 批准号:
    11470393
  • 财政年份:
    1999
  • 资助金额:
    $ 9.28万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B).
Mechanism of osteoclastogenesis inhibitory action by interleukin 18
白细胞介素18抑制破骨细胞生成的机制
  • 批准号:
    09671905
  • 财政年份:
    1997
  • 资助金额:
    $ 9.28万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)

相似国自然基金

Lipopolysaccharide 调节 Toll-like receptor 4 介导促进心肌样细胞存活时间的实验研究
  • 批准号:
    30872544
  • 批准年份:
    2008
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阐明乳酸菌表面层蛋白的抗炎机制,重点关注其与脂多糖的相互作用。
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长期输注牙龈卟啉单胞菌脂多糖诱发心力衰竭的致病机制。
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使用不清楚的磁共振研究噬菌体 phiX174 的刺突蛋白识别脂多糖。
  • 批准号:
    23K04941
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Novel roles for lipopolysaccharide modifications in immune evasion
脂多糖修饰在免疫逃避中的新作用
  • 批准号:
    10592139
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The effects of early adolescent lipopolysaccharide administration on the behaviour of male and female rats through adolescence and adulthood
青春期早期脂多糖给药对雄性和雌性大鼠青春期和成年期行为的影响
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间充质炎症信号在脂多糖诱导的急性肺损伤期间调节免疫反应和组织功能障碍
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Illuminating the essential role of the outer membrane component and drug target, lipopolysaccharide
阐明外膜成分和药物靶点脂多糖的重要作用
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研究静脉输液疗法和伊马替尼给药对人静脉内脂多糖(LPS)脓毒症模型的影响。
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Development of a mechanistically novel Gram-negative antibiotic targeting MsbA-mediated Lipopolysaccharide Biogenesis
开发一种机制新颖的革兰氏阴性抗生素,靶向 MsbA 介导的脂多糖生物发生
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