Fig. 8: Scheme of the mode of damaged brain accelerates bone healing by releasing sEVs that target osteoprogenitors.

After TBI, the injured neurons released osteogenic miRNA-enriching sEVs, which were transferred to bone through the circulatory system, and target osteoprogenitors to promote osteogenesis and accelerate bone healing. The increased FN1 expression on sEVs surface contributed to direct sEVs to target osteoprogenitors. miR-328a-3p and miR-150-5p enriched in plasma sEVs after TBI were strong osteogenic miRNAs, which had potent potential to repair bone by directly targeting FOXO4 and CBL 3′-UTR, respectively.