The elementary fusion modalities of osteoclasts
The elementary fusion modalities of osteoclasts
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DOI：
10.1016/j.bone.2014.12.010
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发表时间：
2015-04-01
期刊：
影响因子：
4.1
通讯作者：
Delaisse, Jean-Marie
中科院分区：
文献类型：
--
作者：
Soe, Kent;Hobolt-Pedersen, Anne-Sofie;Delaisse, Jean-Marie
破骨细胞分化过程的最后一步是细胞融合。了解融合机制的大多数努力都集中在鉴定参与融合过程的分子上。令人惊讶的是，已知用于融合其他细胞类型的基本融合方式对于破骨细胞是未知的。在这里，我们表明，破骨细胞融合的合作伙伴的特点是不同的流动性，核和分化水平。我们的演示是基于来自三个供体的人类破骨细胞制备物的时间段视频，其中分析了656个融合事件。移动的和非移动的伙伴之间的融合最频繁（62%），而两个移动的（26%）或两个非移动的伙伴（12%）之间的融合不太频繁（p < 0.001）。一般而言，非移动的融合伴侣比移动的融合伴侣含有更多的细胞核（p < 0.01）。此外，在67%的病例中，具有三个或更多个核的破骨细胞的核富集是由于与单核细胞融合（p < 0.001），而在61%的病例中，单核细胞与多核细胞融合（p < 0.05）。这一观察结果表明，更成熟的破骨细胞更倾向于与不太成熟的前破骨细胞融合。这一假设得到了核示踪方法在更多和更少分化的前破骨细胞/破骨细胞的共培养的支持。此外，我们发现破骨细胞融合主要通过两种不同类型的细胞接触进行：吞噬杯和广泛接触表面（>80%的融合）。我们的结论是，破骨细胞最经常获得一个细胞核的时间，除了一个细胞核，这是最经常由一个移动的细胞传递到一个不动的细胞。这些特征符合体内观察，其中从骨髓迁移的单核前体与位于骨表面的更成熟的破骨细胞融合。它们也适合其他细胞类型的融合模式。(C)2014爱思唯尔公司All rights reserved.
The last step of the osteoclast differentiation process is cell fusion. Most efforts to understand the fusion mechanism have focused on the identification of molecules involved in the fusion process. Surprisingly, the basic fusion modalities, which are well known for fusion of other cell types, are not known for the osteoclast. Here we show that osteoclast fusion partners are characterized by differences in mobility, nuclearity, and differentiation level. Our demonstration was based on time-laps videos of human osteoclast preparations from three donors where 656 fusion events were analyzed. Fusions between a mobile and an immobile partner were most frequent (62%), while fusion between two mobile (26%) or two immobile partners (12%) was less frequent (p < 0.001). In general, the immobile fusion partner contained more nuclei than the mobile one (p < 0.01). Furthermore, enrichment in nuclei of an osteoclast with three or more nuclei resulted from fusion with a mono-nucleated cell in 67% of the cases (p < 0.001), while mono-nucleated cells fused with a multinucleated cell in 61% of the cases (p < 0.05). This observation suggested that a more mature osteoclast prefers to fuse with a less mature pre-osteoclast. This hypothesis was supported by a nucleus-tracing approach in a co-culture of more and less differentiated pre-osteoclasts/osteoclasts. Furthermore, we found that osteoclast fusion proceeds through primarily two different types of cell contacts: phagocytic-cup and broad-contact-surfaces (>80% of all fusions). We conclude that osteoclasts most often gain nuclei by addition of one nucleus at a time, and that this nucleus is most often delivered by a moving cell to an immobile cell. These characteristics fit the in vivo observations where mono-nucleated precursors migrating from the bone marrow fuse with more mature osteoclasts sitting on the bone surface. They also fit the fusion modalities of other cell types. (C) 2014 Elsevier Inc. All rights reserved.