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

Abstract

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.

Treadmill exercise influences the microRNA profiles in the bone tissues of mice

“…As terminally differentiated cells, osteocytes that are mechanically stimulated produce factors such as proteins, peptides and signaling molecules that regulate osteogenic differentiation or bone metabolism (42,43). Mechanical stimuli, such as fluid shear stress, increase the number of exosomes released by osteocytes, these exosomes contain factors such as sclerotinins, NF-κB receptor activators and osteoprotegerin, which regulate osteogenic differentiation (44,45). Cer tain osteocyte-der ived miRNAs, such as miR-218, may influence osteoblastic differentiation (46).…”