Osteoblasts-derived exosomes regulate osteoclast differentiation through miR-503-3p/Hpse axis

Abstract

MicroRNAs (miRNAs) are involved in bone remodeling by regulating the balance of bone formation and resorption. Increasing evidence has confirmed that the communication between osteoclast and osteoblast through secreting exosomes and transferring miRNAs. It has been reported that mineralized osteoblasts release exosomes containing more miR-503-3p. However, the roles and molecular mechanisms of osteoblast exosomes-derived miR-503-3p in osteoclast differentiation remain elusive. Here, we isolated exosomes from the supernatant of osteoblasts and identified the exosome characterization through transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blot assay. In addition, we found that exosomes and miR-503-3p secreted by osteoblasts inhibited the differentiation of osteoclast progenitor cells. Meanwhile, we found that Hpse (heparanase gene) was a target gene of miR-503-3p and miR-503-3p inhibited the osteoclast differentiation through downregulating the expression of Hpse. In summary, our results demonstrated the roles and the mechanism of osteoblast-derived exosomes inhibited the osteoclast differentiation via miR-503-3p/Hpse axis.