Department of Clinical Cell Biology, Vejle Hospital, IRS/CSFU, University of Southern Denmark, Kabbeltoft 25, 7100 Vejle, Denmark.
Bone. 2011 Apr 1;48(4):837-46. doi: 10.1016/j.bone.2010.11.011. Epub 2010 Nov 24.
Generation of osteoclasts through fusion of mono-nucleated precursors is a key event of bone physiology and bone resorption is inefficient without osteoclast fusion. Several factors playing a critical role in the fusion process have already been recognized, but the factors involved in the actual fusion of the lipid bilayers of their cell membranes are still unknown. Syncytin-1 is a protein encoded by a human endogenous retroviral gene which was stably integrated into the human ancestor genome more than 24 million years ago. Upon activation, syncytin-1 is able to destabilize the lipid bilayer of the target cell and to force the merging of plasma membranes. This protein is a key player in the fusion of cytotrophoblasts. In the present study, syncytin-1 as well as its putative receptor ASCT2 was found to be expressed in differentiating osteoclasts in vitro, both on mRNA and protein level. This was documented through Q-PCR, Western blot and immunofluorescence analyses. These in vitro findings were confirmed by immunohistochemical stainings in human iliac crest biopsies. A syncytin-1 inhibitory peptide reduced the number of nuclei per osteoclast by 30%, as well as TRACP activity. From a mechanistic point of view, it is interesting that the distribution of syncytin-1 immunoreactivity on the cell surface parallels that of actin, another important player in cell fusion, and that cell-cell proximity induces particular patterns of distribution of syncytin-1 and actin in the respective cells. These complementary observations support a critical role of syncytin-1 in osteoclast fusion, which is of special interest in view of its well-known ability to force the merging of plasma membranes.
破骨细胞通过单核前体细胞融合产生，这是骨骼生理学的一个关键事件，如果没有破骨细胞融合，骨吸收就不会有效。已经有几个因素被认为在融合过程中起关键作用，但涉及到它们细胞膜脂质双层实际融合的因素仍然未知。Syncytin-1 是一种由人类内源性逆转录病毒基因编码的蛋白质，它在 2400 多万年前就已经稳定地整合到人类祖先的基因组中。激活后，Syncytin-1 能够破坏靶细胞的脂质双层，并迫使质膜融合。这种蛋白质是滋养细胞融合的关键因素。在本研究中，发现在体外分化的破骨细胞中表达 Syncytin-1 及其假定受体 ASCT2，无论是在 mRNA 还是蛋白质水平上。这通过 Q-PCR、Western blot 和免疫荧光分析得到了证明。这些体外发现通过对人髂嵴活检的免疫组织化学染色得到了证实。Syncytin-1 抑制肽可使每个破骨细胞的核数减少 30%，同时还可降低 TRACP 活性。从机制上讲，有趣的是 Syncytin-1 免疫反应性在细胞表面的分布与肌动蛋白（细胞融合的另一个重要参与者）的分布相平行，细胞-细胞接近诱导 Syncytin-1 和肌动蛋白在各自细胞中的特定分布模式。这些互补的观察结果支持 Syncytin-1 在破骨细胞融合中的关键作用，考虑到其众所周知的迫使质膜融合的能力，这一点尤其有趣。
