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

## TL;DR

Mature osteoblasts release vesicles that shift bone metabolism from building to breaking down by inhibiting bone formation and promoting osteoclast activity.

## Contribution

The study identifies small osteoblast vesicles (SOVs) as key mediators of the switch from bone formation to resorption via miR-143.

## Key findings

- SOVs suppress osteoblast differentiation and enhance osteoclastogenesis by increasing RANKL expression.
- miR-143 in SOVs inhibits Runx2 by targeting Cbfb mRNA, a key regulator of osteoblast development.
- SOVs act as extracellular vesicles mediating cell-to-cell communication during bone remodeling.

## 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.

Bone remodeling involves a switch between bone formation and resorption, but the mechanisms is unclear. Here, the authors show that intercellular communication via extracellular vesicles secreted by mature osteoblasts is a key factor for the switching, via a microRNA-mediated mechanism.