Evaluation of osteoclast-derived exosomal miRNA under simulated microgravity conditions using next-generation sequencing

Abstract The important role of osteoclast-derived exosomes in bone remodeling of microgravity-induced osteoporosis has been validated. However, the underlying mechanism remains unclear. A set of total miRNAs expressed in osteoclast-derived exosomes may configure the specific signature of the bone tissue in the microgravity condition. This study aimed to investigate the miRNA expression profile of osteoclast-derived exosomes in simulated microgravity using next-generation sequencing. Cell culture supernatant of osteoclasts under normal gravity conditions and simulated microgravity conditions were harvested for the extraction of exosomes and exosomal miRNAs. Our results revealed that 116 aberrantly expressed exosomal miRNAs including 29 up-regulated miRNAs and 87 down-regulated miRNAs were found in the simulated microgravity group compared to the normal gravity control group. The candidate target genes and signaling pathways of 15 selected differentially expressed miRNAs were identified via target genes prediction, GO and KEGG analyses. Furthermore, miRNA qPCR assay was performed to validate the RNA sequencing results. Collectively, these analyses provide insight regarding the effects of microgravity in modulating the extracellular miRNA profile through exosomes released from osteoclasts. The selective packaging of miRNA cargo in exosomes under microgravity could facilitate the development of promising and effective targets for the diagnosis, prevention, and treatment of microgravity-induced osteoporosis.