Regulating Osteogenic Differentiation by Suppression of Exosomal MicroRNAs.

IMPACT STATEMENT: We investigated the role of exosomes in osteogenesis and the use of miRNA inhibitor-transfected exosomes to control osteogenic differentiation. RNA-sequencing (RNA-seq) of exosomal miRNAs revealed that growth condition of milieu of preosteoblast exosomes harbors high levels of let-7, which plays a critical role in osteogenesis regulation. We modified exosomes by transfecting let-7 inhibitor into exosomes under growth condition in MC3T3-E1 cells and revealed that exosomes whose let-7 was inactivated by engineering lost the ability to recover osteogenic differentiation. Genetically modified exosomes may serve as powerful biomaterials for developmental control, including of osteogenesis regulation.