Research Paper Volume 11, Issue 6 pp 1791—1803

Muscle-derived miR-34a increases with age in circulating extracellular vesicles and induces senescence of bone marrow stem cells

Figure 6. EVs from C2C12 cells overexpressing miR-34a home to bone marrow in vivo and reduce Sirt1 expression ex vivo. (A) Mice were injected via tail vein with DiR dye alone (VEH) or EVs from C2C12 cells overexpressing miR-34a labeled with DiR (EVs + DiR) and imaged with AmiX imaging. Mice receiving labeled EVs show high image intensity in the metaphyseal regions of long bones. (B) Bone marrow cells flushed from untreated mice and cultured in the presence of EVs from miR-34a overexpression cells show reduced Sirt1 expression compared to cells cultured with EVs from control C2C12 cells. (C) Bone marrow cells flushed from untreated mice and cultured in the presence of EVs from miR-34a overexpression cells show reduced Sirt1 protein compared to cells cultured with EVs from control C2C12 cells. Top image is from protein of adherent cells, graph includes pooled data from both adherent and non-adherent cells. *P<.05, **P<.01. (D) Working model summarizing changes in muscle and bone with age, and the role of EV-derived miR-34a in muscle and bone senescence. ROS = reactive oxygen species.