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

我们研究了纯化的骨细胞/基质细胞的骨细胞的特征。从M-CSF缺乏的OP/OP小鼠获得的骨质细胞的OSTEPORTOCTORY的存活不仅刺激了破骨细胞的生存（也是其osteoplasts-osteoplasts osteoperotegerin（4） ODF的更多OY受体（5）破骨细胞表达高水平的IL-1受体和ODF受体（等级）。受体拮抗剂，但不是OPG，而ODF诱导的激活被OPG明确抑制。这些结果表明，成骨细胞/stromal细胞通过成骨细胞激活因子，实际上是ODF，其cDNA在1998年克隆。在Traf6敲除小鼠中，许多骨化的ost骨出现了traf6介导的信号