Research Paper Volume 8, Issue 1 pp 16—30
Vesicular Galectin-3 levels decrease with donor age and contribute to the reduced osteo-inductive potential of human plasma derived extracellular vesicles
- 1 Christian Doppler Laboratory for Biotechnology of Skin Aging, Department of Biotechnology, BOKU - University of Natural Resources and Life Sciences Vienna, 1190 Vienna, Austria
- 2 Evercyte GmbH, 1190 Vienna, Austria
- 3 Department of Nanobiotechnology, BOKU - University of Natural Resources and Life Sciences Vienna, 1190 Vienna, Austria
- 4 Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria
- 5 Red Cross Blood Transfusion Service of Upper Austria, Austria
- 6 Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Center, 1200 Vienna, Austria
- 7 Austrian Cluster for Tissue Regeneration, Austria
Received: November 12, 2015 Accepted: November 29, 2015 Published: January 9, 2016https://doi.org/10.18632/aging.100865
How to Cite
Aging results in a decline of physiological functions and in reduced repair capacities, in part due to impaired regenerative power of stem cells, influenced by the systemic environment. In particular osteogenic differentiation capacity (ODC) of mesenchymal stem cells (MSCs) has been shown to decrease with age, thereby contributing to reduced bone formation and an increased fracture risk.
Searching for systemic factors that might contribute to this age related decline of regenerative capacity led us to investigate plasma-derived extracellular vesicles (EVs). EVs of the elderly were found to inhibit osteogenesis compared to those of young individuals. By analyzing the differences in the vesicular content Galectin-3 was shown to be reduced in elderly-derived vesicles. While overexpression of Galectin-3 resulted in an enhanced ODC of MSCs, siRNA against Galectin-3 reduced osteogenesis. Modulation of intravesicular Galectin-3 levels correlated with an altered osteo-inductive potential indicating that vesicular Galectin-3 contributes to the biological response of MSCs to EVs. By site-directed mutagenesis we identified a phosphorylation-site on Galectin-3 mediating this effect. Finally, we showed that cell penetrating peptides comprising this phosphorylation-site are sufficient to increase ODC in MSCs. Therefore, we suggest that decrease of Galectin-3 in the plasma of elderly contributes to the age-related loss of ODC.