Abstract
MicroRNAs have an important role in bone homeostasis. However, the detailed mechanism of microRNA-mediated intercellular communication between bone cells remains elusive. Here, we report that osteoclasts secrete microRNA-enriched exosomes, by which miR-214 is transferred into osteoblasts to inhibit their function. In a coculture system, inhibition of exosome formation and secretion prevented miR-214 transportation. Exosomes specifically recognized osteoblasts through the interaction between ephrinA2 and EphA2. In osteoclast-specific miR-214 transgenic mice, exosomes were secreted into the serum, and miR-214 and ephrinA2 levels were elevated. Therefore, these exosomes have an inhibitory role in osteoblast activity. miR-214 and ephrinA2 levels in serum exosomes from osteoporotic patients and mice were upregulated substantially. These exosomes may significantly inhibit osteoblast activity. Inhibition of exosome secretion via Rab27a small interfering RNA prevented ovariectomized-induced osteoblast dysfunction in vivo. Taken together, these findings suggest that exosome-mediated transfer of microRNA plays an important role in the regulation of osteoblast activity. Circulating miR-214 in exosomes not only represents a biomarker for bone loss but could selectively regulate osteoblast function.
Highlights
Bones undergo constant turnover throughout our lifespan
To characterize the vesicles released during osteoclastogenesis, mouse osteoclast progenitor RAW 264.7 cells were induced by RANKL for 2 days
We identified a mechanism of osteoclast-mediated suppression of osteoblasts through miRNA-containing exosomes
Summary
Bones undergo constant turnover throughout our lifespan. Bone homeostasis is precisely controlledIn bones, microRNAs (miRNAs) regulate multiple processes, including osteoblast and osteoclast differentiation, orchestration of bone programming and management of cell fate [12]. miRNAs were first determined to be present in the cytoplasm. The ability of exosomes to incorporate and transfer miRNAs indicates their ability to influence the physiological behavior of recipient cells [28, 29]. They have important roles in various biological processes [30,31,32,33], including cancer progression, immune regulation and tissue repair. Their roles in bone remodeling have not yet been reported
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