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  Osteoblast-derived vesicles induce a switch from bone-formation to bone-resorption in vivo

Uenaka, M., Yamashita, E., Kikuta, J., Morimoto, A., Ao, T., Mizuno, H., et al. (2022). Osteoblast-derived vesicles induce a switch from bone-formation to bone-resorption in vivo. NATURE COMMUNICATIONS, 13(1): 1066. doi:10.1038/s41467-022-28673-2.

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 Creators:
Uenaka, Maki, Author
Yamashita, Erika, Author
Kikuta, Junichi, Author
Morimoto, Akito, Author
Ao, Tomoka, Author
Mizuno, Hiroki, Author
Furuya, Masayuki, Author
Hasegawa, Tetsuo, Author
Tsukazaki, Hiroyuki, Author
Sudo, Takao, Author
Nishikawa, Keizo, Author
Okuzaki, Daisuke, Author
Motooka, Daisuke, Author
Kosaka, Nobuyoshi, Author
Sugihara, Fuminori, Author
Boettger, Thomas1, Author              
Braun, Thomas1, Author              
Ochiya, Takahiro, Author
Ishii, Masaru, Author
Affiliations:
1Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591695              

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 Abstract: Bone metabolism is regulated by the cooperative activity between bone-forming osteoblasts and bone-resorbing osteoclasts. However, the mechanisms mediating the switch between the osteoblastic and osteoclastic phases have not been fully elucidated. Here, we identify a specific subset of mature osteoblast-derived extracellular vesicles that inhibit bone formation and enhance osteoclastogenesis. Intravital imaging reveals that mature osteoblasts secrete and capture extracellular vesicles, referred to as small osteoblast vesicles (SOVs). Co-culture experiments demonstrate that SOVs suppress osteoblast differentiation and enhance the expression of receptor activator of NF-kappa B ligand, thereby inducing osteoclast differentiation. We also elucidate that the SOV-enriched microRNA miR-143 inhibits Runt-related transcription factor 2, a master regulator of osteoblastogenesis, by targeting the mRNA expression of its dimerization partner, core-binding factor beta. In summary, we identify SOVs as a mode of cell-to-cell communication, controlling the dynamic transition from bone-forming to bone-resorbing phases in vivo.

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 Dates: 2022-02-24
 Publication Status: Published online
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 Identifiers: ISI: 000769633800013
DOI: 10.1038/s41467-022-28673-2
PMID: 35210428
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Title: NATURE COMMUNICATIONS
Source Genre: Journal
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Pages: - Volume / Issue: 13 (1) Sequence Number: 1066 Start / End Page: - Identifier: -