MCP-1 expressed by osteoclasts stimulates osteoclastogenesis in an autocrine/paracrine manner
MCP-1 expressed by osteoclasts stimulates osteoclastogenesis in an autocrine/paracrine manner
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DOI：
10.1016/j.bbrc.2009.04.020
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发表时间：
2009-06-05
影响因子：
3.1
通讯作者：
Miyamoto, Takeshi
中科院分区：
文献类型：
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作者：
Miyamoto, Kana;Ninomiya, Ken;Miyamoto, Takeshi
单核细胞趋化蛋白-1 （MCP-1）是一种趋化因子，在白细胞的募集和激活中起着关键作用。在这里，我们描述了mcp -1缺陷小鼠的细胞中多核破骨细胞的形成被显著抑制。MCP-1参与破骨细胞-细胞融合的调控；然而，缺乏DC-STAMP（破骨细胞-细胞融合所必需的7跨膜受体）的小鼠细胞中多核破骨细胞形成的缺陷并没有被重组MCP-1修复。破骨细胞缺乏MCP-1导致DC-STAMP、NFATc1表达下调。和组织蛋白酶K，这些都在正常破骨细胞中高表达，表明mcp -1缺陷细胞的破骨细胞分化受到抑制。单独MCP-1不能诱导破骨细胞生成，但加入重组MCP-1后，MCP-1缺失细胞的破骨细胞生成抑制得以恢复，说明在破骨细胞RANKL的刺激下，MCP-1以自分泌/旁分泌的方式调节破骨细胞生成。(C) 2009爱思唯尔公司版权所有。
Monocyte chemoattractant protein-1 (MCP-1) is a chemokine that plays a critical role in the recruitment and activation of leukocytes. Here, we describe that multinuclear osteoclast formation was significantly inhibited in cells derived from MCP-1-deficient mice. MCP-1 has been implicated in the regulation of osteoclast cell-cell fusion; however defects of multinuclear osteoclast formation in the cells from mice deficient in DC-STAMP, a seven transmembrane receptor essential for osteoclast cell-cell fusion, was not rescued by recombinant MCP-1. The lack of MCP-1 in osteoclasts resulted in a down-regulation of DC-STAMP, NFATc1. and cathepsin K, all of which were highly expressed in normal osteoclasts, suggesting that osteoclast differentiation was inhibited in MCP-1-deficient cells. MCP-1 alone did not induce osteoclastogenesis, however, the inhibition of osteoclastogenesis in MCP-1-deficient cells was restored by addition of recombinant MCP-1, indicating that osteoclastogenesis was regulated in an autocrine/paracrine manner by MCP-1 under the stimulation of RANKL in osteoclasts. (C) 2009 Elsevier Inc. All rights reserved.