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Bone Abstracts (2014) 3 PP112 | DOI: 10.1530/boneabs.3.PP112

1University of Natural Resources and Life Sciences, Vienna, Austria; 2Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Vienna, Austria; 3Evercyte GmbH, Vienna, Austria; 4Institute of Biomedical Aging Research, Austrian Academy of Sciences, Innsbruck, Austria; 5Children’s Cancer Research Institute (CCRI), St. Anna Kinderkrebsforschung, Vienna, Austria; 6Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands; 7Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University, Vienna, Austria; 8Department of Pathophysiology, Medical University, Vienna, Austria.

Aging is a complex process that results in the decline of physiologic functions due to accumulation of damage in cells and tissues. Mesenchymal stem cells (MSCs) counteract this decline but their regeneration capacity decreases with age. In particular osteogenic differentiation potential of MSCs has been shown to decrease with age thereby contributing to slowed down bone formation and osteoporosis. While much is known about cellular aging of MSCs, little is known about factors of the aged systemic environment influencing their functionality.

While searching for extrinsic factors that influence osteogenesis of MSCs extracellular vesicles (EVs) were found.

Exposition of MSCs to EVs secreted by senescent endothelial cells (senECs), which were shown to accumulate with age in vivo, or isolated from plasma of human elderly donors failed to induce osteogenesis compared to MSCs incubated with secreted EVs of young endothelial cells or plasma derived EVs of young donors. We attributed the age-dependent impairment of osteogenesis by EVs to vesicular miR-31 which was shown to be enriched within EVs of senECs and within plasma derived EVs of elderly donors but also in EVs of patients suffering from osteoporosis.

Overexpression of miR-31 in MSCs reduced osteogenic differentiation capacity while inhibiting miR-31 enhanced osteogenesis in vitro. MiR-31s underlying molecular inhibitory effect was illuminated by demonstrating that miRNA-31 targets FZD3, a factor which was previously unknown to be necessary for osteogenesis. Finally we were able to rescue MSCs from the inhibitory effect of EVs isolated from senECs or from plasma of elderly donors by transfecting them with a miR-31 inhibitor.

Summarizing our data suggest that vesicular miR-31 is enriched within EVs of elderly donors as well as in the case of osteoporosis and that it is able to inhibit osteogenesis. Thus it might serve as a diagnostic and therapeutic target whenever osteogenesis is a limiting factor

Volume 3

European Calcified Tissue Society Congress 2014

Prague, Czech Republic
17 May 2014 - 20 May 2014

European Calcified Tissue Society 

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