Secreted microvesicular miR-31 inhibits osteogenic differentiation of mesenchymal stem cells

Sylvia Weilner; Elisabeth Schraml; Matthias Wieser; Paul Messner; Karl Schneider; Klemens Wassermann; Lucia Micutkova; Klaus Fortschegger; Andrea B Maier; Rudi Westendorp; Heinrich Resch; Susanne Wolbank; Heinz Redl; Pidder Jansen-Dürr; Peter Pietschmann; Regina Grillari-Voglauer; Johannes Grillari

doi:10.1111/acel.12484

Secreted microvesicular miR-31 inhibits osteogenic differentiation of mesenchymal stem cells

Sylvia Weilner, Elisabeth Schraml, Matthias Wieser, Paul Messner, Karl Schneider, Klemens Wassermann, Lucia Micutkova, Klaus Fortschegger, Andrea B Maier, Rudi Westendorp, Heinrich Resch, Susanne Wolbank, Heinz Redl, Pidder Jansen-Dürr, Peter Pietschmann, Regina Grillari-Voglauer, Johannes Grillari

90 Citations (Scopus)

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.

Original language	English
Journal	Aging Cell
Volume	15
Issue number	4
Pages (from-to)	744–754
Number of pages	11
ISSN	1474-9718
DOIs	https://doi.org/10.1111/acel.12484
Publication status	Published - 1 Aug 2016

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Weilner, S., Schraml, E., Wieser, M., Messner, P., Schneider, K., Wassermann, K., Micutkova, L., Fortschegger, K., Maier, A. B., Westendorp, R., Resch, H., Wolbank, S., Redl, H., Jansen-Dürr, P., Pietschmann, P., Grillari-Voglauer, R., & Grillari, J. (2016). Secreted microvesicular miR-31 inhibits osteogenic differentiation of mesenchymal stem cells. Aging Cell, 15(4), 744–754. https://doi.org/10.1111/acel.12484

Weilner, S, Schraml, E, Wieser, M, Messner, P, Schneider, K, Wassermann, K, Micutkova, L, Fortschegger, K, Maier, AB, Westendorp, R, Resch, H, Wolbank, S, Redl, H, Jansen-Dürr, P, Pietschmann, P, Grillari-Voglauer, R & Grillari, J 2016, 'Secreted microvesicular miR-31 inhibits osteogenic differentiation of mesenchymal stem cells', Aging Cell, vol. 15, no. 4, pp. 744–754. https://doi.org/10.1111/acel.12484

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title = "Secreted microvesicular miR-31 inhibits osteogenic differentiation of mesenchymal stem cells",

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.",

author = "Sylvia Weilner and Elisabeth Schraml and Matthias Wieser and Paul Messner and Karl Schneider and Klemens Wassermann and Lucia Micutkova and Klaus Fortschegger and Maier, {Andrea B} and Rudi Westendorp and Heinrich Resch and Susanne Wolbank and Heinz Redl and Pidder Jansen-D{\"u}rr and Peter Pietschmann and Regina Grillari-Voglauer and Johannes Grillari",

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T1 - Secreted microvesicular miR-31 inhibits osteogenic differentiation of mesenchymal stem cells

AU - Weilner, Sylvia

AU - Schraml, Elisabeth

AU - Wieser, Matthias

AU - Messner, Paul

AU - Schneider, Karl

AU - Wassermann, Klemens

AU - Micutkova, Lucia

AU - Fortschegger, Klaus

AU - Maier, Andrea B

AU - Westendorp, Rudi

AU - Resch, Heinrich

AU - Wolbank, Susanne

AU - Redl, Heinz

AU - Jansen-Dürr, Pidder

AU - Pietschmann, Peter

AU - Grillari-Voglauer, Regina

AU - Grillari, Johannes

PY - 2016/8/1

Y1 - 2016/8/1

N2 - 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.

AB - 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.

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DO - 10.1111/acel.12484

M3 - Journal article

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SN - 1474-9718

VL - 15

SP - 744

EP - 754

JO - Aging Cell

JF - Aging Cell

IS - 4

ER -

Secreted microvesicular miR-31 inhibits osteogenic differentiation of mesenchymal stem cells

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