Evaluation of the cargo contents and potential role of extracellular vesicles in osteoporosis

Abstract

Osteoporosis is a common aging-related disease diagnosed primarily using bone mineral density (BMD). Extracellular vesicles (EVs) remain unexplored in the context of osteoporosis. Towards this, EVs were isolated from plasma of a discovery cohort with 8 non-osteoporotic and 8 osteoporotic individuals, and nanoparticle tracking analysis (NTA) revealed a significantly higher EV concentration in osteoporotic individuals (<i>P</i> = 0.003). Moreover, EVs concentration showed a linear correlation with bone mineral density (BMD) values (linear correlation coefficient <i>r</i> = 0.9542, deviation from zero, <i>p</i> < 0.001). Results using a mouse model of osteoporosis confirmed that the number of EVs in mice from hindlimb unloading group was significantly higher than that from the age-matched control group (<i>p</i> = 0.015). TaqMan Real-Time PCR demonstrated that miR-335-5p, -320a, -483-5p, and miR-21-5p, were significantly higher expressed in osteoporotic patients compared with non-osteoporotic individuals. Quantitative real-time PCR shown that Wnt1, Wnt5a, Wnt7a, and Wnt9a mRNAs were lower expressed in osteoporosis derived EVs. <i>In vitro</i> functional assay indicated that osteoporosis derived EVs resulted in reduced mineralization in SaOS-2 cells. In conclusion, these results suggest that osteoporosis increased the secretion of EVs which carry higher expression of miRNAs and decreased expression of Wnt signals, further decreased the mineralization capacity in human osteoblasts.