Table 2.

Odontoblast-like cytodifferentiation of dental mesenchymal stem cells through chemical introduction

Introduced chemical(s)	Cell type	Source	Experiment	ALP activity	Mineralization	Gene/Protein marker 1			References
Inflammatory Cytokines (TNFα and IL-1β)	DPSC	Human	In vitro	-	N	ALP, NES, and DSPP *The results were verified by NF-κB knock-down.			Hozhabri et al. [32]
Strontium	DPSC	Human	In vitro	+	+	DSPP, RUNX2, OCN, MEPE, BMP2, and ON			Huang et al. [33]
Ca 2+	DPSC	Human	In vitro	-	+	BSP/BSP, OCN/OCN, DMP1, and DSPP *BMP/Smad pathway is involved in the Ca2+-induced odontoblast-like differentiation of DPSCs.			Li et al. [34]
LPS	DPSC	Human	In vitro	N	+	OCN, DMP1, DSPP, and ALP *LPS promotes odontoblast-like differentiation via TLR4, ERK, and P38 MAPK signaling pathways.			He et al. [35]
BMP2	DPSC	Human	In vitro, in vivo	N	+	DSPP, DMP1, PHEX, MMP20 *Increased odontoblast-like cells, vascularization, and dentin matrix formation were observed at the areas, in which treated cells were transplanted.			Atalayin et al. [36]
MMP2-CLEAVAGE OF DMP1	DPSC	Human	In vitro, in vivo	N	N	DSP, DMP1 *Implantation of this peptide in a rat injured pulp model resulted in dentin-like structure formation.			Chaussain et al. [37]
FGF2 and TGF- β	DPSC	Human	In vitro	+	+	DSP/DSP, DMP1/DMP1 * FGF and TGF-β co-treatment improves odontoblast-like differentiation inducing potential.			Unda et al. [97]
Insulin-like growth factor	DPSC	Human	In vitro	+	+	OSX/OSX, RUNX2/RUNX2, OCN/OCN, DSPP, DSP			LV et al. [38]
Platelet lysate	DPSC	Human	In vitro, in vivo	+	+	N			Chen et al. [39]
Semaphorin 4D	DPSC	Human	In vitro	-	-	COL1/COL1, DSPP/DSPP, ALP, BSP, RUNX2			Zou et al. [40]
Recombinant LOXL2	DPSC	Human	In vitro	-	-	ALP, DMP1, and DSPP			Kim et al. [41]
Trichostatin A (histone deacetylase inhibitor)	DPSC	Human	In vitro, in vivo	+	+	DSPP, DMP1, BSP			Jin et al. [42]
EDTA (cells were seeded on dentin slices)	DPSC	Human	In vitro	N	+	DMP1 and DSPP *EDTA induced cell attachment.			Pang et al. [43]
Ca(OH) 2 and NaOCl &EDTA (cells were seeded on dentin slices)	DPSC	Human	In vitro	N	N	DSPP and DMP1 *Ca(OH)2 and EDTA promoted the differentiation of DPSCs after NaOCl treatment.			Park et al. [44]
Conditioned dentine slice and powder by EDTA, phosphoric acid, citric acid	DPSC	Human	In vitro	N	+	ALP and OPN			Sadaghiani et al. [45]
Ethanol	DPSC	Human	In vitro, in vivo	-	-	BMP2, BMP4, OCN, OPN, ALP, DLX2 *Ethanol induced inhibition of KDM6B (a lysine demethylase). As a result, odontogenic differentiation is down regulated.			Hoang et al. [46]
Preameloblast-conditioned medium	DPSC	Human	In vitro, in vivo	N	+	DSP, NES, COL1			Lee et al. [47]
Human and swine tooth germ cell conditioned medium	DPSC	Human	In vitro, in vivo	+	+	OPN, DSPP, DMP1/DMP1, OCN, BSP, DSP			Wang et al. [48]
Ginsenoside Rg1	DPSC	Human	In vitro	N	N	BMP2/BMP2, FGF2/FGF2, DSPP, ALP, OCN			Wang et al. [49]
Zinc containing bioactive glasses	DPSC	Human	In vitro	+	+	RUNX2, OCN, MEPE, BMP2, BSP, ON, DSPP, DMP1			Huang et al. [50]
MTA	DPSC	Human	In vitro	N	N	BSP, ALP, OCN, COL1, DSPP *MTA can induce odontoblast-like differentiation via mitogen-activated protein kinase pathway.			Zhao et al. [51]
MTA	DPSC	Hunan	In vitro	N	+	DMP1 and DSPP *Microarray analysis is done and list of differentially expressed genes which their differences are more than 4-fold are shown.			Seo et al. [52]
MTA and CEM	DPSC	Human	In vitro	N	+	DSPP, DMP1, BMP2, TGF-β1, FGF4 *These chemicals stimulate different gene expression.			Asgary et al. [53]
MTA	SCAP	Human	In vitro, in vivo	+	+	OCN/OCN, RNX2/RUNX2, ALP, DSPP, DSP *MTA can induce odontoblast-like differentiation via Nuclear Factor Kappa B signaling pathway.			Yan et al. [54]
HEMA and TEDGMA	SCAP	Human	In vitro	-	-	BSP, OCN, DSPP			Bakopoulou et al. [55]
Basic FGF	SCAP	Human	In vitro	-	-	BSP, ALP, OCN, OCN, DSPP *This growth factor increases stemness of hSCAPs.			Wu et al. [56]
Insulin-like growth factor	SCAP	Human	In vitro, in vivo	+	+	OCN/OCN, OSX/OSX, RUNX2/RUNX2, ALP		DSPP, DSP	Wang et al. [57]
BMP2	SCAP	Human	In vitro, in vivo	+	+	BSP, OCN, COL1, and DSPP *Seeding cells on nanofibrous microspheres (NF-MS) in combination with controlled release of BMP-2 results in more mineralized tissue formation.			Wang et al. [58]
Recombinant human plasminogen activator inhibitor-1	SCAP	Human	In vitro, in vivo	+	+	ALP, COL1, OPN, OCN, BSP, DMP1			Jin et al. [59]
Conditioned medium from periapical follicle cells	SCAP	Human	In vitro	+	+	DSPP, ALP, OCN			Wu et al. [60]
Dexamethasone-releasing chitosan nanoparticle (Conditioned dentine)	SCAP	Human	In vitro	N	+	DMP1 and DSPP *Increasing dexamethasone releasing velocity results in odontogenic differentiation inducing potential.			Shrestha et al. [61]
Platelet lysate	DPSC, SCAP	Human	In vitro	+	+	DSPP, OPN *SCAPs show more potential for odontogenic differentiation.			Abuarqoub et al. [62]
Platelet-rich plasma	DPSC, PDLSC	Human	In vitro	+	+	BSP, OPN, CEMP1, and DSPP			Lee et al. [63]
BMP2 and dental slice scaffold	SHED	Human	In vitro, in vivo	N	N	DSPP, DMP1, MEPE *After BMP treatment, SHED express BMP receptors.			Casagrande et al. [64]
MEPE-derived ASARM (phosphorylated form)	SHED	Human	In vitro, in vivo	N	-	ALP, MEPE/MEPE	DSPP, DSP, OCN/OCN		Salmon et al. [65]
HEMA and TEDGMA	SHED	Human	In vitro	-	-	BSP, ALP, OCN, DSPP			Bakopoulou et al. [66]
EMD	TGSC	Human	In vitro	+	N	DSPP			Guven et al. [67]
MTA				-		DSPP
Aminated mesoporous bioactive nanoparticles	DPSC	Rat	In vitro	+	+	BSP, OCN, COL1, DMP1 and DSPP			Lee et al. [68]
TNF-α	BMP9-Induced SCAPs	Rat	In vitro, in vivo	-	-	OCN, OPN			Wang et al. [69]

(Chemicals, Proteins, and Genes; TNF-α: tumor necrosis factor alpha, IL-1β: Interleukin 1 beta, LPS: Lipopolysaccharide, BMP: bone morphogenetic protein, MMP: matrix metalloproteinase, DMP: Dentin matrix acidic phosphoprotein, FGF: fibroblast growth factor, TGF-β: transforming growth factor β, LOXL1: Lysyl oxidase homolog 1, EDTA: Ethylenediaminetetraacetic acid, MTA: mineral trioxide aggregate, HEMA: 2-hydroxyethyl methacrylate, TEDGMA: Tri-ethylene-glycol-dimethacrylate, MEPE: Matrix extracellular phosphoglycoprotein, ASARM: serine- and aspartic acid-rich motif, EMD: enamel matrix derivative, ALP: alkaline phosphatase, NES: Nestin, DSPP: dentin sialophosphoprotein, Runx2: Runt-related transcription factor 2, OCN: osteocalcin, ON: osteonectin, BSP: bone sialoprotein, PHEX: Phosphate-regulating neutral endopeptidase, X-linked, DSP: dentin sialoprotein, OSX: Transcription factor Sp7 which is also called Osterix, COL1: Collagen type I, OPN: osteopontin, DLX: Distalless, CEMP: cementum protein. Cells; DPSCs: dental pulp stem cells, SCAP: stem cells from the apical papilla, PDLSC: periodontal ligament stem cells, SHED: stem cells from exfoliated deciduous teeth, TGSC: tooth germ stem 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.