Table 1.
Odontoblast-like cytodifferentiation of dental mesenchymal stem cells through genetic manipulation
| Manipulated gene(s) | Cell type | Source | Vector | Experiment | ALP activity | Mineralization | Gene/Protein marker 1 | References | |
|---|---|---|---|---|---|---|---|---|---|
| BBX | DPSC | Human | Electroporation (+)2 | In vitro | + | + | ALP, OPN, BSP, DMP1, and DSPP | Choi et al.[10] | |
| DELTA1 | DPSC | Human | Lentivirus (-)3 | In vitro | + | + | DSPP | Wang et al.[11] | |
| CX43 | DPSC | Human | Lentivirus (+) | In vitro | N | N |
DSPP/DSPP *CX43 overexpression amplified the extracellular Ca-induced mRNA and protein levels of DSPP. |
Li et al.[12] | |
| TWIST1 | DPSC | Human | Lentivirus (+) | In vitro | N | + | OCN, DMP1, DSP, and OPN *TWIST1 overexpression stimulates DMP1 and DSPP promoter activities. |
Li et al.[13] | |
| VEGF | DPSC | Human | Lentivirus (+) | In vitro | N | N | ALP, OCN, DSPP, DMP1/DMP1, and DSP | Zhang et al.[14] | |
| ORAI1 | DPSC | Human | Lentivirus (-), Retrovirus (-) | In vitro, in vivo | - | - | OCN, DMP1, and BSP | Sohn et al.[15] | |
| INTEGRIN-α5 | DPSC | Human | Lentivirus (-) | In vitro | N | + | ALP, OCN, DMP1, ON, BSP, and DSPP/DSPP | Cui et al.[16] | |
| PIN1 | DPSC | Human | Adenovirus (+) | In vitro | - | - |
ALP, OPN, OCN, DMP1, and DSPP *The results were verified by PIN1 inhibitor (Juglone) treatment. |
Lee et al.[17] | |
| BCL2 | DPSC | Human | Lentivirus (+) | In vitro | - | - | ALP, OCN, DMP1, BSP, COL1 | Heng et al.[18] | |
| NFIC | SCAP | Human | Lentivirus (+) | In vitro | + | + | ALP, OCN, COL1, and DSP | Zhang et al.[19] | |
| NFIC | SCAP | Human | Lipofectamine (-) | In vitro | N | N | DMP1 | DSPP | Gao et al.[20] |
| *Expression of ALP, OCN and COL1 was not significantly changed | |||||||||
| ZHX2 | SCAP | Human | pcDNA3 (+) | In vitro | + | N |
RUNX2/RUNX2, OCN/OCN, BSP/BSP, and DSPP/DSPP *The results were verified by knocking down the ZHX2. |
Wan et al.[21] | |
| BMP2 | SCAP | Human | Lentivirus (+) | In vitro | + | + | ALP, OCN, DSPP, and DMP1 | Zhang et al.[22] | |
| BMP2 and/or VEGF | SCAP | Human | Lentivirus (+) | In vitro | N | + |
ALP, OCN, DSPP, DMP1, and DSP *Expression of odontogenic markers was significantly higher in co-transfected SCAPs |
Zhang et al.[23] | |
| KDM6B | SCAP | Human | Lentiviruses (-) | In vitro | - | - |
OSX, OPN, OCN, and ALP *The results were verified by over expressing the KDM6B |
Xu et al.[24] | |
| BMI1 | Senescent DPSC and SCAP | Human | Retrovirus (+) | In vitro | + | + |
OCN, DSPP, BSP, and DMP1 *Bmi1 transduction enhances odontogenic differentiation capacity in senescent dental MSCs |
Mehrazarin et al.[25] | |
| CREB | SCAP | Human | Lentivirus (+) | In vitro | N | + |
ALP, COL1, OCN, OSX, RUNX2/RUNX2, and DSP *The results were verified by silencing the CREB |
Su et al.[26] | |
| Cav1.2 | DPSC | Rat | Lentiviruses (-) | In vitro | - | - |
DSPP
*The results were verified by L-type calcium channel blocker (Nimodipine) treatment. |
Ju et al.[27] | |
| Human BMP2 | DPSC | Rat | Adenovirus (+) | In vitro | + | + | ALP, OCN, COL1, BSP, DSPP, and DMP1 | Yang et al.[28] | |
| BMP9 | iSCAP | Mouse | Adenovirus (+) | In vitro, in vivo | + | + |
OCN, OPN, BSP, DMP1, DSPP, and MEPE *Ectopic mineralized tissue formation was seen |
Wang et al.[29] | |
|
NFIC
cells were cultured in TGF-β1 treated medium |
SCAP | Mouse | pLenti6.3 (+) | In vitro | + | + |
ALP, OCN, and COL1 *Overexpression of NFIC antagonized the inhibition of odontogenic effects of TGF-β1 on SCAPs, while knockdown of NFIC enhanced these effects |
He et al.[30] | |
| β-Catenin | BMP9- and Wnt3A- induced SCAPs | Mouse | Transposon-based vector (-) (for β-Catenin) | In vitro, in vivo | - | - |
RUNX2/OPN *Silencing β-Catenin expression significantly diminishes BMP9-induced odontoblast-like differentiation of iSCAP cells |
Zhang et al.[31] | |
(Genes and Proteins; BBX: HMG box-containing protein 2, DELTA-1: Notch ligand Delta1, CX43: connexin 43, TWIST1: Twist-related protein 1, VEGF: vascular endothelial growth factor, ORAI1: Calcium release-activated calcium channel protein 1, PIN1: Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1, BCL2: B-cell lymphoma 2, NFIC: Nuclear factor 1 C-type, ZHX2: Zinc fingers and homeoboxes protein 2, BMP: bone morphogenetic protein, KDM6B: Lysine demethylase 6B, BMI1: B cell-specific Moloney murine leukemia virus integration site 1, CREB: cAMP response element-binding protein, Cav1.2: L-type calcium channel a1C subunit, WNT5A: wingless-type MMTV integration site family member 5A, ALP: alkaline phosphatase, OPN: osteopontin, BSP: bone sialoprotein, DMP: Dentin matrix acidic phosphoprotein, DSPP: dentin sialophosphoprotein, OCN: osteocalcin, DSP: dentin sialoprotein, ON: osteonectin, COL1: Collagen type I, Runx2: Runt-related transcription factor 2, OSX: Transcription factor Sp7 which is also called Osterix, MEPE: Matrix extracellular phosphoglycoprotein. Cells; DPSCs: dental pulp stem cells, SCAP: stem cells from the apical papilla, iSCAP: immortalized mouse dental apical papilla progenitor cells. Assays; (+): significant increase compared to control group, (-): significant decrease compared to control group, N: not evaluated.) 1: Regular cells represent gene/protein marker upregulation, shaded cells represent gene/protein marker downregulation, 2: (+) overexpressed, 3: (-) knocked down