Table 2.
Underlying mechanisms of EVs in the dental tissue regeneration
| Functional effects | EVs source | EVs cargos | Involved signaling pathway | Outcome in vitro | References |
|---|---|---|---|---|---|
| Odontogenesis | DPSCs | BMP-2, BMP-9 | P38 MAPK | DSPP | [76] |
| DPSCs | miR-27a-5p | TGFβ-1/Smads | DSP↑, DMP-1 ↑ | [98] | |
| DPSCs | NFIC | – | DSPP↑, DMP-1 ↑, ALP↑, NFSC ↑ | [97] | |
|
DPSCs (under inflammatory environment) |
miR-758-5p | BMP | DSPP↑, DMP-1 ↑ | [99] | |
| Hertwig’s epithelial root sheath cells | Wnt3a | Wnt/β-catenin | DSPP↑, DMP-1 ↑ | [78] | |
| Osteogenesis | ADMSCs | CGRP | - | RUNX2↑, ALP↑, OCN↑ | [58] |
| Plasma | miR-129-5p | FZD4/β-catenin | RUNX2↑, ALP↑, OPN↑ | [104] | |
| DFCs | – | PLC/PKC/MAPK | ALP↑, OCN↑, OPN↑, MMP-2↑ | [65] | |
| DFCs | – | P38 MAPK | RUNX2↑, ALP↑, BSP↑, COL1↑ | [64] | |
|
DPSCs (osteogenic-induced conditioned) |
hsa-miR-31 | – | RUNX2↑, COL1↑, OSX↑ | [139] | |
|
DPSCs (under inflammatory environment) |
miR-758-5p | BMP | RUNX2↑, ALP↑, OCN↑ | [99] | |
|
GMSCs (TNF-α treated) |
miR-1260b | NF-κB | RANKL/OPG↓ | [39] | |
| M2-Macrophage | IL-10 | IL-10/IL-10R | RUNX2↑, ALP↑, OCN↑, COL1a1↑ | [56] | |
| Osteocyte | miR-181b-5p | PTEN/AKT | RUNX2↑, BMP-2↑, AKT1↑, P13KCA↑ | [103] | |
| PDLSCs | Gsk3β | NF-κB | ALP↑, OCN↑, BMP-2↑ | [101] | |
| PDLSCs | Gsk3β | Wnt | OCN↑, RUNX2↑ | [68] | |
| SCAPs | miR-935 | – | OCN↑, OPN↑ | [63] | |
| SHEDs | - | AMPK | RUNX2↑, OPN↑, COL1↑ | [69] | |
| SHEDs | TFAM mRNA | – | RUNX2↑, ALP↑, BMP-2↑ | [102] | |
| UMSCs | – | P13k/AKT | RUNX2↑, ALP↑, OCN↑ | [105] | |
| Mineralization | 17IIA11 cell lines | – | Erk1/2 | Ca2+, Pi formation | [108] |
| Ameloblast | PHOSPHO1 | – | Enamel width↑, Interrod distance↓ | [84] | |
| Incisor epithelial and mesenchymal cells | miR-135a | Wnt/β-catenin | COLIV↑, laminin↑, ALP↑, DSP↑, Bglap↑, Mineral nodule formation | [89] | |
| T4-4 cell lines | IRES | – | DSPP↑, DMP-1↑,DPP↑ | [109] | |
| Angiogenesis |
DPSCs (from periodontally diseased teeth) |
– | P38 MAPK | VEGF↑, MMP-9↑, KDR↑, | [114] |
| DPSCs | TUFM | – | VEGF↑, ANG-2↑, MMP-9↑, HIF-1α↑ | [81] | |
| PDLSCs | miR-17-5p | – | VEGFA↑ | [111] | |
| SHEDs | – | AMPK | CD31↑, COL1↑ | [69] | |
| SCAPs | Cdc42 | – | CD31↑, vascular limen formation | [50] | |
| SHEDs | miR-26a | TGFβ/Smad2/3 | VEGF↑, ANG-2↑, PDGF↑, | [75] | |
|
SHEDs (hypoxic-preconditioned) |
let-7f-5p, miR-210-5p |
AGO/VEGF; miR-210-3p/ephrinA3 |
VEGF↑, MMP-9↑, ANGPT1↑ | [113] | |
| Immunomodulation | BMMSCs | – | OPG-RANKL-RANK |
Arginase↑, CD163↑, TGF-β1↑, iNOS↓, CD86↓ |
[55] |
|
DFCs (LPS-preconditioned) |
– | ROS/JNK | RANKL/OPG↓ | [71] | |
| DPSCs | miR-125a-3p | TLR, NF-κB |
IL-1ra↑, IL-10↑, IL-1β↓, IL-6↓, TNF-α↓ |
[118] | |
| DPSCs | miR-1246 |
NF-κB p65, p38 MAPK |
CD206↑, Arginase↑, CD163↑, IL-1β↓, IL-6↓, TNF-α↓, iNOS↓, CD86↓ |
[61] | |
| DPSCs | miR-1246 | – | Th17/Treg↓ | [62] | |
| Dendritic cells | TGF-β, IL-10 | – | Th17/Treg↓ | [59] | |
| EBCs | CD73 | AKT/ERK, AMPK | MMP13↓, NO↓, s-GAG↑ | [92] | |
| GMSCs | – | NF-κB p65, Wnt5a | TNF-α↓, IL-1β↓, IL-10↑ | [140] | |
| PDLSCs | – | NF-κB | IL-1β↓ | [116] | |
| PDLSCs | miR-155-5p | – | Th17/Treg↓, RORC↓, STRT1↓, FOXP3↑ | [38] | |
| SHEDs | miR-100-5p | – | IL-6↓, IL-8↓, MMP-1↓, MMP-3↓, MMP-9↓, MMP-13↓ | [94] | |
| SCAPs | miR-935 | – | IL-6↓, IL-8↓ | [63] | |
| Salivary | miR-25-3p | IL-17↓ | [37] |