Muscle-derived miR-34a increases with age in circulating extracellular vesicles and induces senescence of bone marrow stem cells. Aging Extracellular vesicles (EVs) are known to play important roles in cell-cell communication. Here we investigated the role of muscle-derived EVs and their microRNAs in the loss of bone stem cell populations with age. Aging in male and female C57BL6 mice was associated with a significant increase in expression of the senescence-associated microRNA miR-34a-5p (miR-34a) in skeletal muscle and in serum -derived EVs. Muscle-derived, alpha-sarcoglycan positive, EVs isolated from serum samples also showed a significant increase in miR-34a with age. EVs were isolated from conditioned medium of C2C12 mouse myoblasts and primary human myotubes after cells were treated with hydrogen peroxide to simulate oxidative stress. These EVs were shown to have elevated levels of miR-34a, and these EVs decreased viability of bone marrow mesenchymal (stromal) cells (BMSCs) and increased BMSC senescence. A lentiviral vector system was used to overexpress miR-34a in C2C12 cells, and EVs isolated from these transfected cells were observed to home to bone and to induce senescence and decrease Sirt1 expression of primary bone marrow cells . These findings suggest that aged skeletal muscle is a potential source of circulating, senescence-associated EVs that may directly impact stem cell populations in tissues such as bone via their microRNA cargo. 10.18632/aging.101874

-AC-l-Leu-PEI-mediated miR-34a delivery improves osteogenic differentiation under orthodontic force. Yu Wenwen,Zheng Yi,Yang Zhujun,Fei Hongbo,Wang Yang,Hou Xu,Sun Xinhua,Shen Yuqin Oncotarget Rare therapeutic genes or agents are reported to control orthodontic bone remodeling. MicroRNAs have recently been associated with bone metabolism. Here, we report the and effects of miR-34a on osteogenic differentiation under orthodontic force using an -acetyl-L-leucine-modified polyethylenimine (-Ac-l-Leu-PEI) carrier. -Ac-l-Leu-PEI exhibited low cytotoxicity and high miR-34a transfection efficiency in rat bone mineral stem cells and local alveolar bone tissue. After transfection, miR-34a enhanced the osteogenic differentiation of and , Runx2 and ColI protein levels, and early osteogenesis function under orthodontic strain . MiR-34a also enhanced alveolar bone remodeling under orthodontic force , as evidenced by elevated gene and protein expression, upregulated indices of alveolar bone anabolism, and diminished tooth movement. We determined that the mechanism miR-34a in osteogenesis under orthodontic force may be associated with GSK-3β. These results suggested that miR-34a delivered by -Ac-l-Leu-PEI could be a potential therapeutic target for orthodontic treatment. 10.18632/oncotarget.22790