权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Study on osteoclast activiting factor expressed by osteoblasts/stromal cells

成骨细胞/基质细胞表达的破骨细胞激活因子的研究

基本信息

批准号：
10470394
负责人：
TAKAHASHI Naoyuki
金额：
$ 8.26万
依托单位：
Showa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

项目摘要

We have investigated characteristics of osteoclast activating factor expressed by osteoblasts/stromal cells. The method for obtaining a large number of purified mononuclear and multinucleated osteoclasts was established in this study. Using the purification method, we analyzed the mechanism of activation of osteoclasts by osteoblasts/stromal cells.(1) Osteoblasts enhanced survival of purified mononuclear and multinucleated osteoclasts, which resulted in formation of multinucleated osteoclasts. Osteoblasts also stimulated resorption pit-forming activity of osteoclasts through a mechanism involving cell-to-cell contact.(2) M-CSF produced by osteoblasts also stimulated the survival of osteoclasts, but failed to stimulated pit-forming activity of osteoclasts.(3) Osteoblasts obtained from M-CSF-deficient op/op mice stimulated not only survival of osteoclasts but also their pit-forming activity.(4) Osteoblast-induced pit forming activity of osteoclasts was inhibited by osteoprotegerin (a dec … More oy receptor for ODF) simultaneously added.(5) Osteoclasts expressed high levels of IL-1 type 1 receptors and ODF receptors (RANK). Treatment of osteoclasts with IL-1 or ODF induced activation of NF-κB.(6) IL-1 and ODF stimulated pit-forming activity of osteoclasts. IL-1 -induced osteoclast activation was inhibited by IL-1 receptor antagonist but not OPG, whereas ODF-induced osteoclast activation was specifically inhibited by OPG.These results indicate that osteoclast activating factor expressed by osteoblasts/stromal cells is indeed ODF, the cDNA of which cloned in 1998. Recently, it was shown that TRAF6 knockout mice developed severe osteopetrosis. In TRAF6 knockout mice, many osteoclasts were found in bone but they failed to develop ruffled borders. As IL-1 receptors and RANK are shown to be interact with TRAF6, TRAF6-mediated signals appear to be important for IL-1 and RANK-induced activation of osteoclasts. It is also suggested that activation of NF-KB is important for induction of pit-forming activity of osteoclasts. Less

我们研究了成骨细胞/基质细胞表达的破骨细胞激活因子的特征。本研究建立了获得大量纯化的单核和多核破骨细胞的方法。利用纯化方法，我们分析了成骨细胞/基质细胞激活破骨细胞的机制。(1)成骨细胞增强了纯化的单核和多核破骨细胞的存活率，从而导致多核破骨细胞的形成。成骨细胞还通过细胞与细胞接触的机制刺激破骨细胞的吸收凹坑形成活性。(2)成骨细胞产生的M-CSF也刺激破骨细胞的存活，但不能刺激破骨细胞的凹坑形成活性。(3)刺激从M-CSF缺陷的op/op小鼠获得的成骨细胞不仅影响破骨细胞的存活，而且影响其成坑活性。(4)同时添加的骨保护素(ODF的dec… More oy受体)抑制破骨细胞诱导的破骨细胞成坑活性。(5)破骨细胞表达高水平的IL-1 1型受体和ODF受体(RANK)。 IL-1或ODF处理破骨细胞可诱导NF-κB的激活。(6)IL-1和ODF刺激破骨细胞的小凹形成活性。 IL-1诱导的破骨细胞活化被IL-1受体拮抗剂抑制，但OPG不被抑制，而ODF诱导的破骨细胞活化被OPG特异性抑制。这些结果表明，成骨细胞/基质细胞表达的破骨细胞活化因子确实是ODF，其cDNA于1998年克隆。最近，研究表明TRAF6基因敲除小鼠出现严重的石骨症。在 TRAF6 敲除小鼠中，在骨骼中发现了许多破骨细胞，但它们未能形成褶皱边界。由于 IL-1 受体和 RANK 被证明与 TRAF6 相互作用，因此 TRAF6 介导的信号似乎对于 IL-1 和 RANK 诱导的破骨细胞激活很重要。还表明NF-KB的激活对于诱导破骨细胞的小坑形成活性很重要。较少的