The therapeutic effects of MSC-EVs on periodontitis. MSC-EVs deliver multiple cargoes (eg, miRNAs, proteins, etc.) to different recipient cells, including osteoblasts, cementoblasts, MSCs, and ECs. Multiple underlying mechanisms are involved in MSC-EV-mediated osteogenesis, angiogenesis, cell migration/proliferation, and cementogenesis. These signaling pathways regulate biological processes in recipient cells to exert therapeutic effects on periodontitis. Abbreviations: AKT, protein kinase B; AMP, adenosine monophosphate; AMPK, AMP-activated protein kinase; BMP2, bone morphogenetic protein 2; Ckip-1, casein kinase 2 interacting protein-1 EGF, epidermal growth factor; ERK, extracellular signal-regulated kinase; HIF-1α, hypoxia-inducible factor 1-alpha; IGFBP-3/5/6, insulin-like growth factor binding protein-3/5/6; MAPK, mitogen-activated protein kinase; NF-κB, the nuclear factor kappa-light-chain-enhancer of activated B cells; OPG, osteoprotegerin; p-AKT, the phosphorylation of AKT; p-AMPK, the phosphorylation of AMPK; PI3K, phosphoinositide 3-kinase; p-JNK, the phosphorylation of c-Jun N-terminal kinase; PKC, protein kinase C; PLC, phospholipase C; p-Smad1/5/8/9, the phosphorylation of Smad1/5/8/9; RANK, receptor activator of nuclear factor κB; RANKL, the receptor activator of nuclear factor κ ligand; STAT1, signal transducer and activator of transcription 1; TUFM, Tu translation elongation factor; VCAM-1, vascular cell adhesion molecule-1; VEGF, vascular endothelial growth factor; Wnts, wingless protein.