Osteosarcoma-derived exosomal miR-501-3p promotes osteoclastogenesis and aggravates bone loss

Emerging evidence indicates that osteoclasts from osteosarcoma patients have higher tartrate resistant acid phosphatase (TRAP) activity. Exosomes are important mediators of the cell-to-cell communication. However, whether osteosarcoma cell-derived exosomes mediate the osteoclastogenesis of bone marrow-derived monocytes (BMDMs) and its mechanisms are largely unknown. In this research, we validated the communication between osteosarcoma cells and BMDMs. Here, we found that osteosarcoma cell-derived exosomes can be transfered to BMDMs to promote osteoclast differentiation. The miR-501-3p is highly expressed in exosomes derived from osteosarcoma and could be transferred to BMDMs through the exosomes. Moreover, osteosarcoma-derived exosomal miR-501-3p mediate its role in promoting osteoclast differentiation and aggravates bone loss in vitro and in vivo. Mechanistically, osteosarcoma cell-derived exosomal miR-501-3p could promote osteoclast differentiation via PTEN/PI3K/Akt signaling pathway. Collectively, our results suggest that osteosarcoma-derived exosomal miR-501-3p promotes osteoclastogenesis and aggravates bone loss. Therefore, our study reveals a novel mechanism of osteoclastogenesis in osteosarcoma patients and provides a novel target for diagnosis or treatment.