Figure 2.

Schematic representation depicting selected role of exosomes from resident and microenvironment cells in bone remodeling: Hematopoietic precursors such as monocytes secrete exosomes, which stimulate osteoclast differentiation. Mature osteoclast-derived exosomes are enriched with RANK, which competitively inhibits osteoclastogenesis while also inhibiting osteogenesis in early stages. Mesenchymal stem cells secrete exosomes, which promote osteogenesis. MSCs and osteoblasts also secrete RANKL enriched exosomes, which stimulates osteoclastogenesis. Osteoblast-derived exosomes further promote mineralization and osteogenesis. Terminally differentiated osteocytes derived from sub population of osteoblasts promote bone formation under mechanical stress conditions. Cells in microenvironments such as endothelial cells and dendritic cells promote bone formation while inhibiting bone resorption. Macrophages also undergo polarization to stimulate osteogenesis.