Please use this identifier to cite or link to this item: https://doi.org/10.1111/acel.12484
Title: Secreted microvesicular miR-31 inhibits osteogenic differentiation of mesenchymal stem cells
Authors: Weilner, Sylvia
Schraml, Elisabeth
Wieser, Matthias
Messner, Paul
Schneider, Karl
Wassermann, Klemens
Micutkova, Lucia
Fortschegger, Klaus
Maier, Andrea B 
Westendorp, Rudi
Resch, Heinrich
Wolbank, Susanne
Redl, Heinz
Jansen-Durr, Pidder
Pietschmann, Peter
Grillari-Voglauer, Regina
Grillari, Johannes
Keywords: Science & Technology
Life Sciences & Biomedicine
Cell Biology
Geriatrics & Gerontology
aging
mesenchymal stem cells
MicroRNA
osteogenic differentiation
microvesicles
senescence-associated secretory phenotype
HUMAN BONE-MARROW
ENDOTHELIAL-CELLS
MICRORNA EXPRESSION
PROGENITOR CELLS
CANCER-CELLS
SENESCENCE
MECHANISMS
MATURATION
DISEASES
DEFECTS
Issue Date: 1-Aug-2016
Publisher: WILEY
Citation: Weilner, Sylvia, Schraml, Elisabeth, Wieser, Matthias, Messner, Paul, Schneider, Karl, Wassermann, Klemens, Micutkova, Lucia, Fortschegger, Klaus, Maier, Andrea B, Westendorp, Rudi, Resch, Heinrich, Wolbank, Susanne, Redl, Heinz, Jansen-Durr, Pidder, Pietschmann, Peter, Grillari-Voglauer, Regina, Grillari, Johannes (2016-08-01). Secreted microvesicular miR-31 inhibits osteogenic differentiation of mesenchymal stem cells. AGING CELL 15 (4) : 744-754. ScholarBank@NUS Repository. https://doi.org/10.1111/acel.12484
Abstract: Damage to cells and tissues is one of the driving forces of aging and age-related diseases. Various repair systems are in place to counteract this functional decline. In particular, the property of adult stem cells to self-renew and differentiate is essential for tissue homeostasis and regeneration. However, their functionality declines with age (Rando, 2006). One organ that is notably affected by the reduced differentiation capacity of stem cells with age is the skeleton. Here, we found that circulating microvesicles impact on the osteogenic differentiation capacity of mesenchymal stem cells in a donor-age-dependent way. While searching for factors mediating the inhibitory effect of elderly derived microvesicles on osteogenesis, we identified miR-31 as a crucial component. We demonstrated that miR-31 is present at elevated levels in the plasma of elderly and of osteoporosis patients. As a potential source of its secretion, we identified senescent endothelial cells, which are known to increase during aging in vivo (Erusalimsky, 2009). Endothelial miR-31 is secreted within senescent cell-derived microvesicles and taken up by mesenchymal stem cells where it inhibits osteogenic differentiation by knocking down its target Frizzled-3. Therefore, we suggest that microvesicular miR-31 in the plasma of elderly might play a role in the pathogenesis of age-related impaired bone formation and that miR-31 might be a valuable plasma-based biomarker for aging and for a systemic environment that does not favor cell-based therapies whenever osteogenesis is a limiting factor.
Source Title: AGING CELL
URI: https://scholarbank.nus.edu.sg/handle/10635/234993
ISSN: 1474-9726
DOI: 10.1111/acel.12484
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