Human bone marrow stem/stromal cell osteogenesis is regulated via mechanically activated osteocyte-derived extracellular vesicles.

Stem Cells Translational Medicine
Kian EichholzDavid A Hoey

Abstract

Bone formation or regeneration requires the recruitment, proliferation, and osteogenic differentiation of stem/stromal progenitor cells. A potent stimulus driving this process is mechanical loading. Osteocytes are mechanosensitive cells that play fundamental roles in coordinating loading-induced bone formation via the secretion of paracrine factors. However, the exact mechanisms by which osteocytes relay mechanical signals to these progenitor cells are poorly understood. Therefore, this study aimed to demonstrate the potency of the mechanically stimulated osteocyte secretome in driving human bone marrow stem/stromal cell (hMSC) recruitment and differentiation, and characterize the secretome to identify potential factors regulating stem cell behavior and bone mechanobiology. We demonstrate that osteocytes subjected to fluid shear secrete a distinct collection of factors that significantly enhance hMSC recruitment and osteogenesis and demonstrate the key role of extracellular vesicles (EVs) in driving these effects. This demonstrates the pro-osteogenic potential of osteocyte-derived mechanically activated extracellular vesicles, which have great potential as a cell-free therapy to enhance bone regeneration and repair in diseases ...Continue Reading

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Citations

Aug 11, 2021·Experimental and Therapeutic Medicine·Huan YangYong Guo
Aug 24, 2021·Advanced Therapeutics·Stephanie M KronstadtSteven M Jay
Sep 22, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Zilong YaoBin Yu

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Methods Mentioned

BETA
PCR
acetylation
protein assay
confocal microscopy
Assay
PCA

Software Mentioned

MaxQuant
Perseus
Andromeda
BLAST
UCSC Genome Browser
NTA

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