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

Maki Uenaka, Erika Yamashita, Junichi Kikuta (), Akito Morimoto, Tomoka Ao, Hiroki Mizuno, Masayuki Furuya, Tetsuo Hasegawa, Hiroyuki Tsukazaki, Takao Sudo, Keizo Nishikawa, Daisuke Okuzaki, Daisuke Motooka, Nobuyoshi Kosaka, Fuminori Sugihara, Thomas Boettger, Thomas Braun, Takahiro Ochiya and Masaru Ishii ()
Additional contact information
Maki Uenaka: Osaka University
Erika Yamashita: Osaka University
Junichi Kikuta: Osaka University
Akito Morimoto: Osaka University
Tomoka Ao: Osaka University
Hiroki Mizuno: Osaka University
Masayuki Furuya: Osaka University
Tetsuo Hasegawa: Osaka University
Hiroyuki Tsukazaki: Osaka University
Takao Sudo: Osaka University
Keizo Nishikawa: Osaka University
Daisuke Okuzaki: Osaka University
Daisuke Motooka: Osaka University
Nobuyoshi Kosaka: Tokyo Medical University
Fuminori Sugihara: Osaka University
Thomas Boettger: Max-Plank-Institute for Heart and Lung Research
Thomas Braun: Max-Plank-Institute for Heart and Lung Research
Takahiro Ochiya: Tokyo Medical University
Masaru Ishii: Osaka University

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: 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-κB 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 β. 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.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28673-2

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DOI: 10.1038/s41467-022-28673-2

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