Hepatocyte growth factor can substitute for M-CSF to support osteoclastogenesis
Hepatocyte growth factor can substitute for M-CSF to support osteoclastogenesis
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DOI：
10.1016/j.bbrc.2006.09.076
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发表时间：
2006-11-17
影响因子：
3.1
通讯作者：
Athanasou, Nicholas A.
中科院分区：
文献类型：
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作者：
Adamopoulos, Iannis E.;Xia, Zhidao;Athanasou, Nicholas A.
缺乏功能性巨噬细胞集落刺激因子（M-CSF）的骨硬化小鼠随着年龄的增长而恢复，这表明存在替代的破骨细胞生成途径。肝细胞生长因子（HGF）和M-CSF通过酪氨酸激酶受体和磷酸化常见的转换器和效应器（如Src、Grb 2和PI 3-激酶）发出信号。已知HGF在破骨细胞形成中起作用，在本研究中，我们确定HGF是否可以取代M-CSF来支持人类破骨细胞生成。我们发现HGF受体c-Met由人外周血单核细胞（PBMC）的CD 14（+）单核细胞部分表达。HGF能够在核因子κ B配体的受体激活剂存在下支持单核细胞-破骨细胞分化，如通过形成许多多核抗酒石酸酸性磷酸酶和玻连蛋白受体阳性细胞所证明的，所述细胞形成F-肌动蛋白环并且能够进行泪泡吸收。M-CSF的中和抗体的添加不抑制破骨细胞分化。HGF是一种公认的存活因子，活力测定和活/死染色显示其以类似于M-CSF的方式促进单核细胞和破骨细胞的存活和增殖。我们的研究结果表明，HGF可以替代M-CSF支持人破骨细胞的形成。(c)2006年爱思唯尔公司All rights reserved.
Osteopetrotic mice lacking functional macrophage-colony stimulating factor (M-CSF) recover with ageing, suggesting that alternative osteoclastogenesis pathways exist. Hepatocyte growth factor (HGF) and M-CSF signal through tyrosine kinase receptors and phosphorylate common transducers and effectors such as Src, Grb2, and PI3-Kinase. HGF is known to play a role in osteoclast formation, and in this study we have determined whether HGF could replace M-CSF to support human osteoclastogenesis. We found that the HGF receptor, c-Met, is expressed by the CD14(+) monocyte fraction of human peripheral blood mononuclear cells (PBMC). HGF was able to support monocyte-osteoclast differentiation in the presence of receptor activator for nuclear factor kappa B ligand as evidenced by the formation of numerous multinucleated tartrate-resistant acid phosphatase and vitronectin receptor positive cells which formed F-actin rings and were capable of lacumar resorption. The addition of a neutralising antibody to M-CSF did not inhibit osteoclast differentiation. HGF is a well-established survival factor and viability assays and live/dead staining showed that it promoted the survival and proliferation of monocytes and osteoclasts in a manner similar to M-CSF. Our findings indicate that HGF can substitute for M-CSF to support human osteoclast formation. (c) 2006 Elsevier Inc. All rights reserved.