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

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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-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.
Funding Information
  • MEXT | Japan Society for the Promotion of Science
  • Japan Agency for Medical Research and Development
  • MEXT | Japan Science and Technology Agency
  • Uehara Memorial Foundation
  • Kanae Foundation for the Promotion of Medical Science
  • Mochida Memorial Foundation for Medical and Pharmaceutical Research
  • Takeda Science Foundation

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