Uptake of osteoblast-derived extracellular vesicles promotes the differentiation of osteoclasts in the zebrafish scale

• Published in: Communications biology Vol. 3; no. 1; p. 190
• Main Authors: Kobayashi-Sun, Jingjing, Yamamori, Shiori, Kondo, Mao, Kuroda, Junpei, Ikegame, Mika, Suzuki, Nobuo, Kitamura, Kei-Ichiro, Hattori, Atsuhiko, Yamaguchi, Masaaki, Kobayashi, Isao
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 23.04.2020; Nature Publishing Group UK
• Subjects: Animal Scales - metabolism; Animals; Animals, Genetically Modified; Biology; Bone healing; Bone imaging; Cell culture; Cell Differentiation; Cell interactions; Cell signaling; Cells, Cultured; Danio rerio; Extracellular vesicles; Extracellular Vesicles - genetics; Extracellular Vesicles - metabolism; Extracellular Vesicles - transplantation; Flow cytometry; Fracture Healing; Fractures; Genes, Reporter; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Luminescent Proteins - genetics; Luminescent Proteins - metabolism; Models, Animal; Molecular modelling; Osteoblastogenesis; Osteoblasts; Osteoblasts - metabolism; Osteoblasts - transplantation; Osteoclastogenesis; Osteoclasts; Osteoclasts - metabolism; Osteogenesis; Red Fluorescent Protein; TRANCE protein; Transplantation; Zebrafish - genetics; Zebrafish - metabolism
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-020-0925-1

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 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.