Figure 4:

Schematic diagram showing the major regulatory growth factors released by exosomes and the changes in tendon that occur aiding the healing process. Blue boxes indicate critical mediators for normal healing and tissue remodeling.²³ Growth factors released by exosomes include: insulin like growth factor 1 (IGF1) which mediates the protein kinase B (PKB/AKT) pathway, forkhead box (FoxO) and mammalian target of rapamycin (mTOR). Transforming growth factor (TGF) activates mothers again decapentaplegic homolog 2 and 3 (SMAD 2/3), P38 mitogen-activated protein kinases (P38-MAPK), signal transducer and activator of transcription 6 (STAT6) and inhibit fibroblast activation protein (FAP) mediated apoptosis. Vascular endothelial growth factor (VEGF) alters transcription of VEGFa, VEGFc, angiopoietin-like 4 (ANGPTL4), TGFα, sphingosine kinase 1 (SPHK1) and cyclooxygenase 2 (COX2). Platelet derived growth factor BB (PDGF-BB) and basic fibroblast growth factor (bFGF). Wnt family member 5 a/b (Wnt5a/b) activate the yes associated protein pathway (YAP).