MicroRNAs-mediated regulation of the differentiation of dental pulp-derived mesenchymal stem cells: a systematic review and bioinformatic analysis

Iranmanesh, Pedram; Vedaei, Amirhossein; Salehi-Mazandarani, Sadra; Nikpour, Parvaneh; Khazaei, Saber; Khademi, Abbasali; Galler, Kerstin M.; Nekoofar, Mohammad-Hossein; Dummer, Paul M. H.

doi:10.1186/s13287-023-03289-5

Stem Cell Research & Therapy

Table 1 Main findings of the studies investigating the promotive or suppressive function of miRNAs on the differentiation of hDP-MSCs through overexpressing or knocking down the miRNAs (studies of group I)

From: MicroRNAs-mediated regulation of the differentiation of dental pulp-derived mesenchymal stem cells: a systematic review and bioinformatic analysis

Author [reference]	miRNA(s)	Type of differentiation; regulatory effect of miRNA(s)		Cell type	Cell source	Growth factor (differentiation inducing agent)	Technique of differentiation assessment	Assessed differentiation markers	Direct target(s) of miRNA(s)	Signaling pathway
Zhong et al. [36]	hsa-miR-140-5p	Odontogenic/osteogenic	↓	hDPSC	Third molar	AA, DEX, BGP	ARS, ALP activity	DSPP, DMP1, RUNX2, ALP	FGF9, BMP2, lncRNA H19	N/A
Bao et al. [50]	hsa-miR-140-5p	Odontogenic/osteogenic	↓	hDPSC	Premolar	AA, DEX, BGP	ARS, ALP staining, VKS	ALP, DSPP, DMP1, desmoplakin, DLX3	GIT2, lncRNA MALAT1	N/A
Wu et al. [60]	hsa-miR-24-3p	Odontogenic/osteogenic	↓	hDPSC	Third molar	BMP2	ARS	RUNX2, OSX, ALP	TGFBR1, LncRNA LEF1-AS1	N/A
Tu et al. [61]	hsa-miR-30b-3p	Odontogenic/osteogenic	↓	hDPSC	Third molar	AA, DEX, BGP	ARS, ALP staining	RUNX2, DSPP, DMP1, ALP	RUNX2, LncRNA CALB2	N/A
Ji et al. [37]	hsa-miR-188-3p	Odontogenic/osteogenic	↓	hDPSC	Third molar	N/R	ARS, ALP staining	OCN, ALP, OSX	Beclin1, Runx1, CircRNA0026827	Beclin1, Runx1
Ji et al. [38]	hsa-miR-496	Odontogenic/osteogenic	↓	hDPSC	Third molar	AA, DEX, BGP	ARS, ALP staining	RUNX2, OCN, ALP	β-catenin, CircRNA124534	β-catenin
Ge et al. [39]	hsa-miR-617	Odontogenic/osteogenic	↓	hDPSC	Third molar	AA, DEX, BGP	ARS, ALP staining	OSX, RUNX2, ALP	SMAD3, CircRNA SIPA1L1	TGF- β/SMAD
Chen et al.* [15]	hsa-miR-588	Odontogenic/osteogenic	↓	hDPSC	Premolar	AA, DEX, BGP	ARS, ALP staining	N/A	FBN1, LncRNA G043225	N/A
Yang et al. [56]	hsa-miR-143-3p	Odontogenic/osteogenic	↓	hDPSC	Third molar and premolar	AA, DEX, BGP	ARS	ALP, DSPP, BSP, OCN, OPN	RANK	OPG/RANKL
Zhang et al. [40]	hsa-miR-206	Odontogenic/osteogenic	↓	hDPSC	Third molar and premolar	AA, DEX, BGP	ARS, ALP staining	RUNX2, OCN, ALP	CircAKT3	N/A
Xie et al. [97]	hsa-miR-31	Odontogenic/osteogenic	↓	hDPSC	Third molar	AA, DEX, BGP	ARS, ALP staining	RUNX2, OCN, COL1	CircLPAR1	N/A
Liao et al. [41]	hsa-miR-3658	Odontogenic/osteogenic	↓	hDPSC	N/R	BMP2	ARS, ALP activity	RUNX2, OSX, ALP	Long intergenic noncoding RNA 00968	N/A
Lu et al. [51]	hsa-miR-140-5p	Odontogenic/osteogenic	↓	hDPSC	Third molar	AA, DEX, BGP	ARS	DSPP, DMP1	Wnt1	Wnt/β-catenin
Zhong et al. [53]	hsa-miR-218	Odontogenic/osteogenic	↓	hDPSC	Third molar and premolar	N/A^a	ELIZA (COL1, OCN, OPN)	COL1, OPN, OCN	LncRNA CCAT1	N/A
Chang et al. [54]	hsa-miR-218	Odontogenic/osteogenic	↓	hDPSC	Third molar	AA, DEX, BGP	ARS	N/A	N/A	MAPK/ERK
Wang et al. [57]	hsa-miR-143-5p	Odontogenic/osteogenic	↓	hDPSC	N/R	AA, DEX, BGP	ARS, ALP staining	DSPP, ALP, OCN	MAPK14	P38 MAPK
Liu et al. [98]	hsa-miR-508-5p	Odontogenic/osteogenic	↓	hDPSC	Third molar	AA, DEX, BGP	ARS, ALP activity	DMP1, DSPP, OCN, ALP	GPNMB	N/A
Zhang et al. [58]	hsa-miR-143	Odontogenic/osteogenic	↓	hDPSC	Third molar	AA, DEX, BGP	ALP activity, ALP staining	ALP, BMP2, RUNX2, COL1	TNF-α	NF-κB
Liu et al. [87]	hsa-let-7c	Odontogenic/osteogenic	↓	hDPSC	Third molar	AA, DEX, BGP	ARS	OCN, OSX, DSPP, RUNX2, ALP, COL1, DMP	IGF-1R	JNK/P38 MAPK
Sun et al. [52]	hsa-miR-140-5p	Odontogenic/osteogenic	↓	hDPSC	Third molar	AA, LPS	ARS, ALP staining	N/A	TLR-4	LPS/TLR-4
Song et al.* [17]	hsa-miR-135b	Odontogenic/osteogenic	↓	hDPSC	Third molar	AA, DEX, BGP	ARS	DSPP, DMP1	Smad4, Smad5	BMP2(Smad5/Smad4)
Gay et al.* [55]	hsa-miR-218	Odontogenic/osteogenic	↓	hDPSC	Third molar	AA, DEX, BGP	ARS	RUNX2	RUNX2	N/A
Chen et al. [63]	hsa-miR-216a	Odontogenic/osteogenic	↑	hDPSC	Third molar	AA, DEX, BGP	ARS	DSPP, DMP1	c-Cbl, LncRNA DANCR	N/A
Zhao et al. [62]	hsa-miR-543	Odontogenic/osteogenic	↑	hDPSC	Third molar	AA, DEX, BGP	ARS, ALP activity	OSX, OPN, OCN, RUNX2, ALP	SMURF1, LncRNA MEG3	SMURF1/ RUNX2
Wang et al. [99]	hsa-miR-125a-3p	Odontogenic/osteogenic	↑	hDPSC	Third molar	AA, DEX, BGP	ARS, ALP staining	ALP, DSPP, DMP1	Fyn	NF-κB, β-catenin
Qiu et al. [75]	hsa-miR-146a-5p	Odontogenic/osteogenic	↑	hDPSC	Third molar and premolar	AA, DEX, BGP	ARS, ALP staining	ALP, RUNX2, OSX, DSPP	NOTCH1	Notch
Huang et al. [100]	hsa-miR-223-3p	Odontogenic/osteogenic	↑	hDPSC	Third molar	AA, DEX, BGP	ARS, ALP activity	DSPP, DMP1, ALP	SMAD3	TGF- β1
Hu et al.* [16]	hsa-miR-27a-5p	Odontogenic/osteogenic	↑	hDPSC	Third molar	AA, DEX, BGP	ARS	DSP, DMP1, ALP, RUNX2	LTBP1	TGF-β/SMAD
Zeng et al. [101]	hsa-miR-675	Odontogenic/osteogenic	↑	hDPSC	premolar	AA, DEX, BGP	ARS, ALP staining, ALP activity	DSPP, DMP1, ALP	DLX3^b	N/A
Xu et al. [59]	hsa-miR-21	Odontogenic/osteogenic	↑	hDPSC	Third molar	TNF-α	ARS, ALP staining	DMP1, DSPP	N/A	STAT3
Ishiy et al. [48]	hsa-miR-1287	Odontogenic/osteogenic	↑	SHED	Human deciduous tooth	N/R	ARS, ALP activity	ALP, RUNX2	N/A	N/A
Dernowsek et al.* [49]	hsa-miR-450a-5p, hsa-miR-28-5p	Odontogenic/osteogenic	↑	SHED	Human deciduous tooth	AA, DEX, BGP	ARS, ALP activity	RUNX2, ALP, BGLAP	STAT1	N/A
Zhang et al. [102]	hsa-miR-633	Odontogenic/osteogenic	↑	hDPSC	Third molar and premolar	N/A^a	Western blot (COL1, OCN, OPN)	COL1, OPN, OCN	MEPE	N/A
Hara et al.* [64]	hsa-miR-720	Odontogenic/osteogenic	↑	hDPSC	Third molar and premolar	AA, DEX, BGP	ARS, ALP staining	DSPP, OPN, ALP	NANOG	N/A
Mehri-Ghahfarrokhi et al. [45]	hsa-miR-124	Neuronal	↑	hDPSC	N/R	BDNF, N2, B27	Microscopy (morphological changes in cells)	Nestin, SOX2, β-tubulin III, MAP2, peripherin	N/A
Wen et al. [44]	hsa-miR-221	Neuronal	↑	SHED	Human deciduous tooth	bFGF, EGF, retinoic acid	Immunohistochemistry (MAP2, Nestin, NSE, neurofilament, tyrosine hydroxylase)	MAP2, Nestin, NSE, neurofilament, tyrosine hydroxylase	CHD8	Wnt/β-catenin
Liu et al. [43]	hsa-miR-140-5p	Neuronal	↓	SHED	Human deciduous tooth	B27, FGF, EGF	Western blot (Nestin, βIII‐tubulin)	MAP2, Nestin, βIII‐tubulin, NSE	BMP2, LncRNA C21orf121	N/A
Wu et al. [42]	hsa-miR-26a-5p	Angiogenic	↑	SHED	Human deciduous tooth	N/A^c	Matrigel assay	VEGF, angiogenin, PDGF, angiopoietin 2	N/A	TGF-β/SMAD2/3
Liu et al. [46]	hsa-miR-424	Angiogenic	↓	hDPSC	Third molar	VEGF	Matrigel assay	vWF, CD31	VEGFR, VEGF
Li et al. [47]	hsa-miR-143, hsa-miR-135	Myogenic	↓	hDPSC	Third molar	Deoxycytidine	Immunofluorescence microscopy (formation of myotubes)	MOG, Myhc, MEF2C, MYOD	MEF2C, MYOD	N/A

↓Suppressive effect
↑Promotive effect
Studies marked with * are in common with Table 2. They have investigated miRNAs expression profile change in addition with studying the regulatory effect of specific miRNAs on the differentiation of hDP-MSCs
^aDifferentiated cell population was compared with stem cell population
^bEpigenetically up-regulated by miRNA
^cSHEDs aggregate-derived exosomes were utilized to induce angiogenic differentiation
AA, Ascorbic acid; ALP, Alkaline phosphatase; ARS, Alizarin red staining; BDNF, Brain-derived neurotrophic factor; bFGF, Basic fibroblast growth factor; BGP, β-glycerolphosphate; BMP2, Bone morphogenetic protein 2; BSP, bone sialoprotein; CHD8, chromodomain helicase DNA-binding protein 8; CircRNA, Circular RNA; COL1, collagen type 1; DEX, Dexamethasone; DLX3, distal-less homeobox 3; DMP1, dentin matrix protein 1; DSP, dentin sialoprotein; DSPP, dentin sialophosphoprotein; EGF, Epidermal growth factor; ERK, Extracellular Receptor Kinase; FBN1, Fibrillin 1; FGF9, Fibroblast growth factor 9; GIT2, G protein–coupled receptor (GPCR)–kinase 2 interacting protein 2; GPNMB, glycoprotein non-metastatic melanomal protein B; hDPSC, Human dental pulp stem cells; IGF-1R, insulin-like growth factor type 1 receptor; lncRNA, Long noncoding RNA; LPS, lipopolysaccharide; LTBP1, Latent Transforming Growth Factor Beta Binding Protein 1; MAP2, Microtubule-associated protein 2; MAPK, mitogen-activated protein kinase; MEF2C, Myocyte Enhancer Factor 2C; MEPE, Matrix extracellular phosphoglycoprotein; Myhc, Myosin heavy chain; MYOD, myoblast determination protein 1; MYOG, Myogenin; N/A, not applicable; NF-κB, nuclear factor kappa light chain enhancer of activated B cells; NOTCH1, Notch homolog 1; N/R, not reported; NSE, neuron-specific enolase; OCN, osteocalcin; OPG: osteoprotegerin; OPN, osteopontin; OSX, osterix; PDGF, Platelet-derived growth factor; RANK, Receptor activator of NF-kB; RANKL, RANK ligand; RUNX, runt-related transcription factor; SHED, Stem cells from human exfoliated deciduous teeth; SMURF1, Smad ubiquitin regulatory factor 1; SOX2, SRY-Box Transcription Factor 2; STAT, signal transducer and activator of transcription; TGF, transforming growth factor; TGFBR1, transforming growth factor-beta (TGF-β) receptor type 1; TLR-4, Toll-like receptor 4; TNF-α, tumor necrosis factor alpha; VEGF, vascular endothelial growth factor; VEGFR, vascular endothelial growth factor receptor; VKS, von Kossa staining; vWF, von Willebrand factor

Back to article page

ISSN: 1757-6512

Contact us

Submission enquiries: Access here and click Contact Us
General enquiries: info@biomedcentral.com