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Updated: Mar 21, 2026
Isolation of Mesenchymal Stem Cells from Human Alveolar Periosteum and Effects of Vitamin D on Osteogenic Activity of Periosteum-derived Cells
Published on: May 4, 2018
Secreted microvesicular miR-31 inhibits osteogenic differentiation of mesenchymal stem cells
Sylvia Weilner1,2,3, Elisabeth Schraml1, Matthias Wieser1,4
1Department of Biotechnology, BOKU - University of Natural Resources and Life Sciences Vienna, Muthgasse 18, 1190, Vienna, Austria.
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.
Insights
Aging impairs bone formation as elderly microvesicles inhibit mesenchymal stem cell differentiation. Elevated plasma miR-31 from senescent cells drives this inhibition, suggesting miR-31 as a biomarker for aging and poor osteogenesis.
Area of Science:
- Cellular aging and regenerative medicine
- Biomarkers for age-related diseases
- Skeletal biology and tissue homeostasis
Background:
- Cellular damage and functional decline are hallmarks of aging and age-related diseases.
- Adult stem cell functionality, crucial for tissue repair, diminishes with age.
- The skeleton is particularly affected by age-related decline in stem cell differentiation.
Purpose of the Study:
- To investigate the impact of circulating microvesicles on mesenchymal stem cell osteogenic differentiation in an age-dependent manner.
- To identify specific factors within microvesicles that mediate age-related inhibition of osteogenesis.
- To explore the potential of microvesicular components as biomarkers for aging and bone health.
Main Methods:
- Analysis of microvesicle effects on mesenchymal stem cell osteogenic differentiation.
- Identification and quantification of microRNA (miR-31) in plasma and microvesicles.
- Investigation of senescent endothelial cells as a source of microvesicular miR-31.
- Validation of miR-31's inhibitory mechanism on osteogenic differentiation via Frizzled-3 target knockdown.
Main Results:
- Circulating microvesicles from elderly donors inhibit mesenchymal stem cell osteogenic differentiation.
- miR-31 was identified as a key mediator of this inhibitory effect.
- Plasma miR-31 levels are elevated in the elderly and in osteoporosis patients.
- Senescent endothelial cells secrete miR-31 within microvesicles, which then inhibit osteogenesis in recipient mesenchymal stem cells by targeting Frizzled-3.
Conclusions:
- Microvesicular miR-31 contributes to age-related impaired bone formation.
- miR-31 may serve as a plasma-based biomarker for aging and systemic conditions unfavorable to osteogenesis.
- Targeting microvesicular miR-31 could be a therapeutic strategy for age-related bone loss.
