The physiological role of osteoclast differentiation factor.
破骨细胞分化因子的生理作用。
基本信息
- 批准号:11470393
- 负责人:
- 金额:$ 3.65万
- 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:1999
- 资助国家:日本
- 起止时间:1999 至 2000
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Osteoprotegerin (OPG), a soluble decoy receptor for receptor activator of nuclear factor-κB ligand (RANKL)/osteoclast differentiation factor (ODF), inhibits both differentiation and function of osteoclasts. We previously reported that OPG-deficient mice exhibited severe osteoporosis caused by enhanced osteoclastic bone resorption. In the present study, potential roles of OPG in osteoclast differentiation were examined using a mouse co-culture system of calvarial osteoblasts and bone marrow cells prepared from OPG-deficient mice. In the absence of bone-resorbing factors, no osteoclasts were formed in co-cultures of wild-type (+/+) or heterozygous (+/-) mouse-derived osteoblasts with bone marrow cells prepared from homozygous (-/-) mice. In contrast, homozygous (-/-) mouse-derived osteoblasts strongly supported osteoclast formation in the co-cultures with homozygous (-/-) bone marrow cells even in the absence of bone-resorbing factors. Addition of OPG to the co-cultures with osteoblasts … More and bone marrow cells derived from homozygous (-/-) mice completely inhibited spontaneously occurring osteoclast formation. Adding 1α, 25-dihydroxyvitamin D3 [1α, 25(OH)2D3] to these co-cultures significantly enhanced osteoclast differentiation. In addition, bone-resorbing activity in organ cultures of fetal long bones derived from homozygous (-/-) mice was markedly increased irrespective of the presence and absence of bone-resorbing factors in comparison with that from wild-type (+/+) mice. Osteoblasts prepared from homozygous (-/-), heterozygous (+/-) and wild-type (+/+) mice constitutively expressed similar levels of RANKL mRNA, which were equally increased by the treatment with 1α, 25(OH)2D3. When homozygous (-/-) mouse-derived osteoblasts and hemopoietic cells were co-cultured, but direct contact between them was prevented, no osteoclasts were formed even in the presence of 1α, 25(OH)2D3 and M-CSF.These findings suggest that OPG produced by osteoblasts/stromal cells is a physiologically important regulator in osteoclast differentiation and function, and that RANKL expressed by osteoblasts functions as a membrane-associated form. Less
骨保护素(Osteoprotegerin, OPG)是核因子-κB配体受体激活因子(RANKL)/破骨细胞分化因子(ODF)的可溶性诱饵受体,可抑制破骨细胞的分化和功能。我们之前报道过opg缺陷小鼠表现出由破骨细胞骨吸收增强引起的严重骨质疏松症。在本研究中,我们使用从OPG缺陷小鼠制备的颅骨成骨细胞和骨髓细胞共培养系统来检测OPG在破骨细胞分化中的潜在作用。在缺乏骨吸收因子的情况下,野生型(+/+)或杂合子(+/-)小鼠来源的成骨细胞与纯合子(-/-)小鼠制备的骨髓细胞共培养均未形成破骨细胞。相比之下,纯合子(-/-)小鼠来源的成骨细胞在与纯合子(-/-)骨髓细胞共培养时,即使在没有骨吸收因子的情况下,也强烈支持破骨细胞的形成。在纯合子(-/-)小鼠骨髓细胞中加入OPG可完全抑制自发发生的破骨细胞形成。在这些共培养物中添加1α, 25-二羟基维生素D3 [1α, 25(OH)2D3]可显著增强破骨细胞的分化。此外,与野生型(+/+)小鼠相比,纯合子(-/-)小鼠的胎儿长骨器官培养物的骨吸收活性明显增加,而不考虑骨吸收因子的存在。纯合子(-/-)、杂合子(+/-)和野生型(+/+)小鼠制备的成骨细胞组成性地表达相似水平的RANKL mRNA,并在1α, 25(OH)2D3处理下均增加。当纯合子(-/-)小鼠来源的成骨细胞与造血细胞共培养,但阻止它们之间的直接接触时,即使在1α, 25(OH)2D3和M-CSF存在下,也没有形成破骨细胞。这些发现表明,成骨细胞/基质细胞产生的OPG是破骨细胞分化和功能的重要生理调节剂,成骨细胞表达的RANKL是一种膜相关形式。少
项目成果
期刊论文数量(42)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Kobayashi, K., Takahashi, N., Jimi, E., Udagawa, N., Takami, M., Kotake, S., Nakagawa, N., Kinosaki, M., Yamaguchi, K., Shima, N., Yasuda, H., Morinaga, T., Higashio, Martin, T.J., Suda, T.: "Tumor necrosis factor α stimulates osteoclast differentiation b
小林,K.,高桥,N.,吉米,E.,宇田川,N.,高见,M.,小竹,S.,中川,N.,城崎,M.,山口,K.,志马,N., Yasuda, H.、Morinaga, T.、Higashio, Martin, T.J.、Suda, T.:“肿瘤坏死因子 α 刺激破骨细胞分化 b
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Udagawa, N., Takahashi, N., Yasuda, H., Mizuno, A., Itoh, K., Ueno, Y., Shinki, T., Gillespie, M.T., Martin, T.J., Higashio, K., Suda, T.: "Osteoprotegerin produced by osteoblasts is an important regulator in osteoclast development and function."Endocrino
宇田川,N.,高桥,N.,安田,H.,水野,A.,伊藤,K.,上野,Y.,新基,T.,吉莱斯皮,M.T.,马丁,T.J.,东尾,K.,须田,
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Itoh, K., Udagawa, N., Matsuzaki, K., Takami, M., Amano, H., Shinki, T., Ueno, Y., Takahashi, N., Suda, T.: "Importance of membrane-or matrix-associated forms of M-CSF and RANKL/ODF in osteoclastogenesis supported by SaOS-4/3 cells expressing recombinant
Itoh, K.、Udakawa, N.、Matsuzaki, K.、Takami, M.、Amano, H.、Shinki, T.、Ueno, Y.、Takahashi, N.、Suda, T.:“膜的重要性-
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Tsurukai,T.,et al.: "Role of macrophage colony- stimulating factor and osteoclast differentiation factor in osteoclastogenesis."J.Bone Miner.Metab.. (in press). (2000)
Tsurukai, T., et al.:“巨噬细胞集落刺激因子和破骨细胞分化因子在破骨细胞生成中的作用。”J.Bone Miner.Metab..(出版中)。
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Jimi,E.,et al.: "Osteoclast differentiation faCtor(ODF)acts as a multifunctional regulator in murine osteoclast differentiation and function."J.lmmunol.. 163. 434-442 (1999)
Jimi,E.,et al.:“破骨细胞分化因子 (ODF) 在小鼠破骨细胞分化和功能中充当多功能调节剂。”J.Immunol.. 163. 434-442 (1999)
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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
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25670793 - 财政年份:2013
- 资助金额:
$ 3.65万 - 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
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$ 3.65万 - 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:
$ 3.65万 - 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:
$ 3.65万 - 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:
$ 3.65万 - 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:
$ 3.65万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
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
- 批准号:
13470394 - 财政年份:2001
- 资助金额:
$ 3.65万 - 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:
$ 3.65万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
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