Fig. 4

Mechanisms of exosomes on TBI injuries. a Exosomes could attenuate early inflammatory response via reducing inflammatory, polarizing macrophage from a pro-inflammatory M1 phenotype to a pro-regenerative M2 phenotype, and reducing inflammatory cytokines release. b Exosomes could enhance cell proliferation and reduce apoptosis. c Exosomes rich in miR-6924-5p could directly inhibit osteoclast formation by binding to the 3′-untranslated regions (3′ UTRs) of OCSTAMP and CXCL12. d Exosome-delivered BMP-2 promotes cartilage differentiation via Smad/RUNX2 signaling pathway. Activation of BMP-2/Smad signaling induces Runx2 expression through the activation of Smad4 and Smad5, after which Runx2 induces the expression of cartilage differentiation-related proteins, Aggrecan, Collagen II, SOX-9, and TIMP-1. e Exosomes promote angiogenesis by activating the VEGF and Hippo signaling pathways. When VEGF binds to the vascular endothelial growth factor receptor (VEGFR), the VEGF‐VEGFR interaction inhibits LATS1/2 and YAP1 phosphorylation by activating the PI3K and MAPK signaling pathways. The leads to increased expression of YAP1 in the nucleus inducing angiogenesis. f Exosomes could reduce fatty infiltration