Human bone marrow mesenchymal stem/stromal cell behaviour is coordinated via mechanically activated osteocyte-derived extracellular vesicles

Osteocytes are mechanosensitive cells that are believed to play a fundamental role in coordinating bone mechanoadaptation via the secretion of paracrine factors. However, the exact mechanisms by which osteocytes relay mechanical signals to effector cells is poorly understood. In this study, we demonstrated that osteocytes subjected to a physiologic fluid shear secrete a distinct collection of factors that significantly enhance human MSC recruitment and osteogenesis. Utilising proteomics we generated an extensive map of proteins within the mechanically activated osteocyte secretome, identifying numerous paracrine factors that are modified by mechanical stimulation. Moreover, we identified the presence of extracellular vesicles (EVs) and further demonstrated that these mechanically activated osteocyte derived EVs (MAEVs) coordinate human MSCs recruitment and osteogenesis. This indicates that mechanical conditioning of parent cells can modify EVs and demonstrates the pro-osteogenic potential of MAEVs as a cell-free therapy to enhance bone regeneration and repair in diseases such as osteoporosis.