Uptake of osteoblast-derived extracellular vesicles promotes the differentiation of osteoclasts in the zebrafish scale
Uptake of osteoblast-derived extracellular vesicles promotes the differentiation of osteoclasts in the zebrafish scale
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DOI：
10.1038/s42003-020-0925-1
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发表时间：
2020-04-23
影响因子：
5.9
通讯作者：
Kobayashi, Isao
中科院分区：
文献类型：
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作者：
Kobayashi-Sun, Jingjing;Yamamori, Shiori;Kobayashi, Isao
破骨细胞（OC）从造血细胞的分化需要与成骨细胞（OB）的细胞相互作用。然而，由于难以在骨中实时成像，OC分化中涉及的细胞间通讯的细胞和分子机制仍然是难以捉摸的。在这里，我们开发了一个骨折愈合模型的规模陷阱：绿色荧光蛋白; osterix：mCherry转基因斑马鱼，以可视化OC和OBs之间的相互作用。移植试验，然后通过流式细胞仪分析显示，大多数陷阱：绿色荧光蛋白（高）OC在骨折规模中检测到的osterix：mCherry（+）部分，因为摄取OB-derived细胞外囊泡（EV）。体内实时成像显示，未成熟OC与osterix：mCherry（+）OB积极相互作用，并在骨折部位会聚之前吞噬EV。体外细胞培养测定显示，OB衍生的EV通过Rankl信号传导促进OC分化。总的来说，这些数据表明，EV介导的与OB的细胞间通讯在骨组织中OC的分化中发挥着重要作用。Kobayashi-Sun等人通过移植试验和实时成像描述了转基因斑马鱼鳞片中骨折骨的愈合，揭示了未成熟的破骨细胞在骨折应力下吞噬成骨细胞衍生的细胞外囊泡（EV），导致破骨细胞分化。这项研究为EV在破骨细胞生成中的作用提供了见解。
Differentiation of osteoclasts (OCs) from hematopoietic cells requires cellular interaction with osteoblasts (OBs). Due to the difficulty of live-imaging in the bone, however, the cellular and molecular mechanisms underlying intercellular communication involved in OC differentiation are still elusive. Here, we develop a fracture healing model using the scale of trap:GFP; osterix:mCherry transgenic zebrafish to visualize the interaction between OCs and OBs. Transplantation assays followed by flow cytometric analysis reveal that most trap:GFP(high) OCs in the fractured scale are detected in the osterix:mCherry(+) fraction because of uptake of OB-derived extracellular vesicles (EVs). In vivo live-imaging shows that immature OCs actively interact with osterix:mCherry(+) OBs and engulf EVs prior to convergence at the fracture site. In vitro cell culture assays show that OB-derived EVs promote OC differentiation via Rankl signaling. Collectively, these data suggest that EV-mediated intercellular communication with OBs plays an important role in the differentiation of OCs in bone tissue.Kobayashi-Sun et al. characterise the healing of fractured bone in the transgenic zebrafish scale by transplantation assays and live imaging, revealing that immature osteoclasts engulf osteoblast-derived extracellular vesicles (EVs) under fracture stress, leading to osteoclast differentiation. This study provides insights into the role of EVs in osteoclastogenesis.