Circulating osteocyte-derived exosomes contain miRNAs which are enriched in exosomes from MLO-Y4 cells

Abstract

Abstract. Signaling molecules produced by osteocytes have been proposed to serve as soluble factors that contribute to bone remodeling, as well as to homeostasis of other organs. However, to the best of our knowledge, there are currently no studies investigating the role of osteocyte-secreted exosomes. In the present study, ablation of osteocytes in mice [osteocyte-less (OL)] was used to examine the microRNA (miRNA) levels of plasma-circulating exosomes. In order to investigate the function of osteocyte-secreted exosomes, exosomes derived from MLO-Y4 cells were extracted and their miRNA expression levels were examined using miRNA array analysis and deep sequencing. Comparison of miRNA expression levels between plasma exosomes from OL mouse plasma and MLO-Y4-derived exosomes revealed that decreases in the number of miRNAs from exosomes circulating in the OL mouse plasma may be caused by a decrease in secretion of exosomes from osteocytes. These results suggest that osteocytes secrete exosomes containing characterized miRNAs and then circulate in the blood, and may thus transfer their components, including miRNAs, to recipient cells where they function as signaling molecules in other organs and/or tissues to regulate biological responses.

Exosome‐derived uterine miR‐218 isolated from cows with endometritis regulates the release of cytokines and chemokines

“…Exosome micro (mi)RNAs, the main molecules playing a regulatory role in exosomes, primarily cause gene silencing in receptor cells (Sato, et al , 2017). A mechanism of the transfer of exosome‐shuttle miRNAs among DCs was previously documented as a means of communication and post‐transcriptional regulation (Montecalvo, et al , 2012).…”

Human bone marrow mesenchymal stem/stromal cell behaviour is coordinated via mechanically activated osteocyte-derived extracellular vesicles

“…Many of the proteins identified in this paper have also been identified in a proteomic analysis of osteoblast released EVs [31, 52]. A previous in vivo study has suggested a role for EVs in systemic signalling, demonstrating altered miRNA expression in EVs isolated from the plasma of osteocyte ablated mice and wild-type mice [24], while other studies have demonstrated the potential for EVs in therapeutics to enhance osteogenic gene expression [53], the use of drug loaded EVs for osteoporosis therapies [27], and the use of EVs for functionalisation of TE scaffolds to enhance bone regeneration [54, 55]. In addition to osteocyte derived MAEVs and the contents driving MSC osteogenesis, MAEVs may also act as sites for mineral nucleation, as has previously been demonstrated in osteoblast EVs [56, 57].…”

“…Interestingly, it has recently been shown that bone cells release EVs and utilise these vesicles as a mechanism to mediate osteoblast and stem/stromal cell osteogenesis [20–23]. Moreover, osteocyte-derived EVs contain miRNAs known to mediate osteoblast function, highlighting a potential non-protein based role in bone cell communication [24, 25]. Bone derived EVs may also be exploited as a potential therapy for various diseases, as well as having potential for treatment of critical size bone defects [26].…”

Bone-Derived Extracellular Vesicles: Novel Players of Interorgan Crosstalk

“…Sato et al compared osteocyte-secreted exosomes and circulating exosomes from osteocyte-less mice. The results indicated that ablation of osteocytes in mice alters the miRNA levels of plasma exosomes (57). This study linked osteocyte exosomes to circulating exosomes, which provides the concept that osteocyte-derived exosomes may transfer their components to other organs.…”