Exosomal Manf originated from endothelium regulated osteoclast differentiation by down- regulating NF-κB signaling pathway

Background Endothelium-derived exosomes has been reported to enhanced osteogenesis. However, the role of endothelial exosomes on osteoclastgenesis is still unknown. Methods Human umbilical vein endothelial cells (HUVECs) were used to isolate exosomes. PBS or HUVEC-Exos were used to treat RAW 264.7 cells. Then, the preconditioned RAW 264.7 cells were subjected to TRAP staining and RT-qPCR assays. In vivo, we constracted osteoporosis mice model. PBS or HUVEC-Exos were injected through tail vein after ovariectomy surgery. Bone mass was assessed by micro-CT and TRAP staining. Furthermore, we conducted RNA sequencing and found the genes that were differentially expressed. Results Osteoclast differentiation was inhibited by endothelium-derived exosomes in this study. Moreover, HUVEC-Exos demonstrated a specific action on bones to promote in vivo bone resorption. Furthermore, exosomal Manf promoted bone resorption via down-regulating NF-κB signaling, and HUVEC-Exos Manf inhibited osteoclast differentiation in vivo . Conclusion HUVEC-exosomal Manf suppressed osteoclastogenesis via down-regulating NF-κB signaling.