TY - JOUR
T1 - Uptake of osteoblast-derived extracellular vesicles promotes the differentiation of osteoclasts in the zebrafish scale
AU - Kobayashi-Sun, Jingjing
AU - Yamamori, Shiori
AU - Kondo, Mao
AU - Kuroda, Junpei
AU - Ikegame, Mika
AU - Suzuki, Nobuo
AU - Kitamura, Kei ichiro
AU - Hattori, Atsuhiko
AU - Yamaguchi, Masaaki
AU - Kobayashi, Isao
N1 - Funding Information:
The authors thank Dr. S. Yuge for supporting intubation anesthesia, Dr. M. Hazawa for supporting cell culture assays, Dr. Y. Furusawa for supporting RNA-seq analysis, and Dr. K. Lewis for critical evaluation of the manuscript. This work was supported in part by Grant-in-Aid for Scientific Research (C) from the Japan Society for the Promotion of Science (18K06331).
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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:GFPhigh 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.
AB - 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:GFPhigh 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.
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U2 - 10.1038/s42003-020-0925-1
DO - 10.1038/s42003-020-0925-1
M3 - Article
C2 - 32327701
AN - SCOPUS:85083793288
SN - 2399-3642
VL - 3
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 190
ER -