You are hereNovember 16, 2020 | Mesenchymal Stem Cells
Osteocyte-derived Extracellular Vesicles – A Novel Approach to Bone Regeneration?
Review of “Human bone marrow stem/stromal cell osteogenesis is regulated via mechanically activated osteocyte-derived extracellular vesicles” from STEM CELLS Translational Medicine by Stuart P. Atkinson
The mechanosensitive osteocytes present in the bone tissue  secrete paracrine acting factors when placed under mechanical stress to regulate the recruitment, proliferation, and osteogenic differentiation of the mesenchymal stem cells (MSCs) required for bone formation or regeneration . Recently, researchers led by David A. Hoey (Trinity College Dublin, Ireland) explored the signaling pathways connecting mechanically stimulated osteocytes and MSCs through a detailed analysis of osteocyte-secreted factors.
Reporting recently in STEM CELLS Translational Medicine , Eichholz et al. now establish the general importance of extracellular vesicles  in driving human MSC recruitment and osteogenesis in response to osteocytes that have been mechanically stimulated by culture under conditions of fluid shear stress. Furthermore, the authors suggest that these findings may prompt the development of a safe and effective cell-free therapeutic approach to bone regeneration and repair for diseases such as osteoporosis [5, 6].
Initial analysis of MSCs cultured in osteocyte conditioned medium revealed that only the secretome released from osteocytes cultured under shear stress conditions significantly induced osteogenesis, thereby supporting the importance of mechanical loading in mediating osteocyte-to-MSC signaling. Interestingly, a proteomic evaluation of the factors secreted by osteocytes revealed the enrichment of proteins associated with extracellular vesicles/exosomes; however, osteocytes cultured under shear stress conditions secreted a greater degree of extracellular vesicle-related proteins than those cultured in static conditions, thereby suggesting a pivotal role for extracellular vesicles in signaling between mechanically stimulated osteocytes and MSCs.
In confirmation of this hypothesis, the fluorescent labeling of osteocyte‐derived extracellular vesicles established their efficient uptake by MSCs. Furthermore, while exposure to extracellular vesicles derived from osteocytes cultured under static conditions prompted a slight improvement in MSC recruitment and osteogenic potential, extracellular vesicles derived from osteocytes cultured under shear stress conditions induced a significantly higher pro-osteogenic effect, as exemplified by significantly increased MSC recruitment, elevated osteogenesis-related gene expression, and enhanced alkaline phosphatase activity.
Overall, the authors provide evidence for the mechanism regulating mechanically‐induced bone formation – stimulated osteocytes secrete extracellular vesicles that induce the recruitment of MSCs and increase their osteogenic potential. These findings also support the exploration of extracellular vesicles derived from mechanically stimulated osteocytes as a safe and effective cell-free therapeutic approach to the induction of bone regeneration and repair in diseases such as osteoporosis.
For more on how osteocyte-derived extracellular vesicles may represent a novel approach to bone regeneration, stay tuned to the Stem Cells Portal!
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