CCL2 and CCR2 are Essential for the Formation of Osteoclasts and Foreign Body Giant Cells
CCL2 and CCR2 are Essential for the Formation of Osteoclasts and Foreign Body Giant Cells
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DOI：
10.1002/jcb.25282
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发表时间：
2016-02-01
影响因子：
4
通讯作者：
Morrison, Nigel A.
中科院分区：
文献类型：
--
作者：
Khan, Usman A.;Hashimi, Saeed M.;Morrison, Nigel A.
破骨细胞是负责骨吸收的多核细胞。它们来自于单核/巨噬细胞谱系中的细胞融合。单核细胞和巨噬细胞也可以融合形成异物巨细胞(FBGC)。在异物反应过程中，异物巨细胞在宿主和异物(如植入物)之间的界面上被观察到。巨噬细胞被不同的细胞因子吸引到骨吸收和异物反应的部位。趋化因子(C-C)配体-2(CCL2)是一种重要的趋化因子，与受体CCR2结合。在这项研究中，我们研究了CCL2和受体CCR2在破骨细胞和FBGC形成中的重要性。CCL2mRNA在巨细胞培养中的表达高于巨噬细胞，在破骨细胞和FBGC中的表达分别是巨噬细胞的9倍和16倍。与野生型相比，CCL2和CCR2基因敲除小鼠骨髓中培养的破骨细胞和FBGC明显减少。在CCL2和CCR2基因敲除小鼠的培养中，不仅巨细胞的数量减少，而且这些细胞的核数量和大小也显著减少。在含有CCL2-/-小鼠骨髓细胞的培养液中加入外源CCL2，可在培养中恢复破骨细胞和FBGC的形成。我们得出结论，CCL2及其受体CCR2对破骨细胞和FBGC的形成具有重要作用，这些基因的缺失导致破骨细胞和FBGC的形成受到抑制。(C)2015年威利期刊公司。
Osteoclasts are multinucleated cells responsible for bone resorption. They are derived from the fusion of cells in the monocyte/macrophage lineage. Monocytes and macrophages can also fuse to form foreign body giant cells (FBGC). Foreign body giant cells are observed at the interface between a host and a foreign body such as implants during a foreign body reaction. Macrophages are attracted to the site of bone resorption and foreign body reactions by different cytokines. Chemokine (C-C) ligand-2 (CCL2) is an important chemotactic factor and binds to a receptor CCR2. In this study we investigated the importance of CCL2 and the receptor CCR2 in the formation of osteoclasts and FBGC. CCL2 mRNA was more highly expressed in giant cell culture than macrophages, being 9-fold and 16-fold more abundant in osteoclasts and FBGC respectively. Significantly fewer osteoclasts and FBGC were cultured from the bone marrow of CCL2 and CCR2 knockout mice, when compared to wild type. Not only were the number of giant cells reduced but there was a significant reduction in the number of nuclei and the size of these cells in the cultures of CCL2 and CCR2 knockout mice. Formation of osteoclasts and FBGC were recovered in cultures by addition of exogenous CCL2 to the media containing marrow cells from CCL2-/- mice. We conclude that CCL2 and its receptor CCR2 are important for the formation of osteoclasts and FBGC and absence of these genes causes inhibition of osteoclast and FBGC formation. (C) 2015 Wiley Periodicals, Inc.