Overview of noncoding RNAs involved in the osteogenic differentiation of periodontal ligament stem cells

Table 2 Overview of ncRNAs involved in the osteogenic differentiation of periodontal ligament stem cells

ncRNAs	Regulatory levels	Modes of action	Associated signaling pathways or biomarkers	Ref.
miR-24-3p	Posttranscriptional regulation	Interacting with Smad5 3′-UTR	Inhibits Smad5 and Runx2, BMP2, OCN biomarkers	Li et al[38] 2019
miR-21	Posttranscriptional regulation	Interacting with Smad5 3′-UTR	Inhibits Smad5 and Runx2, ALP, BSP, OSX biomarkers	Wei et al[39] 2017
		Interacting with Spry1 3′-UTR	Inhibits Spry1 and Runx2, OSX biomarkers	Yang et al[40] 2017
		Interacting with ACVR2B 3′-UTR	Inhibits ACVR2B and enhances Runx2, OCN, ALP biomarkers	Wei et al[56] 2015
miR-203	Posttranscriptional regulation	Interacting with Runx2 3′-UTR	Inhibits Runx2 and ALP, OCN, OPN biomarkers	Feng et al[41] 2019
miR-1305	Posttranscriptional regulation	Interacting with Runx2 3′-UTR	Inhibits Runx2 and ALP, OCN, OPN biomarkers	Chen et al[42] 2017
miR-218	Posttranscriptional regulation	Interacting with Runx2 3′-UTR	Inhibits Runx2 and OCT4, NANOG cytokines	Gay et al[43] 2014
miR-214	Posttranscriptional regulation	Interacting with ATF4 3′-UTR	Inhibits ATF4 and Runx2, ALP, OCN biomarkers	Yao et al[44] 2017
		Interacting with CTNNB1 3′-UTR	Activates Wnt/β-catenin signaling pathway and inhibits ALP, OCN, BSP biomarkers	Cao et al[45] 2017
miR-17	Posttranscriptional regulation	Interacting with TCF3 3′-UTR	Inhibits Runx2, ALP biomarkers	Liu et al[46] 2013
		Interacting with Smurf1 3′-UTR	Activates Smad family proteins and Runx2, ALP, OCN biomarkers	Liu et al[47] 2011
miR-31	Posttranscriptional regulation	Interacting with Stab2 3′-UTR	Inhibits Stab2 and Runx2, OSX, OCN biomarkers	Zhen et al[48] 2017
miR-200c	Posttranscriptional regulation	Interacting with IL-6, IL-1β and CCL-5 3′-UTRs	Inhibits IL-6, IL-1β, CCL-5 and enhances Runx2, ALP, OCN, OPG biomarkers	Hong et al[49] 2016
miR-543	Posttranscriptional regulation	Interacting with TOB2 3′-UTR	Inhibits TOB2 and enhances Runx2, ALP, BSP, COL1A1 biomarkers	Ge et al[50] 2018
miR-22	Posttranscriptional regulation	Interacting with HDAC6 3′-UTR	Inhibits HDAC6 and enhances Runx2, OCN biomarkers	Yan et al[51] 2017
lncRNA TUG1	Transcriptional regulation	Binding with Lin28A protein	Promotes Lin28A and Runx2, ALP, OCN biomarkers	He et al[72] 2018
lncRNA MEG3	Transcriptional regulation	Suppresses BMP2 through binding with hnRNPI protein	Inhibits BMP2 and Runx2, ALP, OCN biomarkers	Liu et al[73] 2019
lncRNA ANCR	Transcriptional regulation	Activates Wnt/β-catenin signaling pathway indirectly	Activates Wnt/β-catenin signaling pathway and inhibits ALP, BSP, DSPP, OCN, Runx2, Gsk3-β biomarkers	Jia et al[74] 2015
	Posttranscriptional regulation	lncRNA ANCR/miR-758/Notch2 axis “ceRNA”	Activates Notch2-Wnt/β-catenin signaling pathway and inhibits ALP, Runx2, OSX biomarkers	Peng et al[78] 2018
	Epigenetic regulation	Interacting with EZH2 and catalysis H3K27me3 of Runx2	Inhibits Runx2 and ALP, OCN biomarkers	Zhu et al[82] 2013
lncRNA POIR	Posttranscriptional regulation	LncRNA POIR/miR 182/FoxO1 axis “ceRNA”	Inhibits TCF-4-Wnt/β-catenin signaling pathway and promotes ALP, Runx2, COL1 biomarkers	Wang et al[77] 2016
lncRNA PCAT1	Posttranscriptional regulation	A feed-forward regulatory loop of lncPCAT1/miR-106a-5p/E2F5/ BMP2 axis “ceRNA”	Activates BMP2 and ALP, Runx2, OSX biomarkers	Jia et al[79] 2019
lncRNA HIF1A‑AS2	Posttranscriptional regulation	Base complementary pairing with the mRNA of HIF-1α	Inhibits HIF-1α and ALP, Runx2 biomarkers	Chen et al[80] 2017
circRNA CDR1as	Posttranscriptional regulation	circRNA CDR1as /miR-7/GDF5 axis “ceRNA”	Enhances Smad1/5/8 and p38 MAPK phosphorylation and promotes ALP, BMP2, Runx2, OCN biomarkers	Li et al[88] 2018
circRNA3140	Posttranscriptional regulation	CircRNA3140/miR-21/ACVR2B axis “ceRNA”	Promotes ACVR2B and inhibits Runx2, OCN, SP7 biomarkers	Wang et al[89] 2019

miRNAs: MicroRNAs; lncRNAs: Long non-coding RNAs; circRNAs: Circular RNAs; hPDLSCs: Human periodontal ligament stem cells; PDLSCs: Periodontal ligament stem cells; Smad5/: SMAD family member 5; Runx2: Runt-related transcription factor 2; BMP2: Bone morphogenetic protein-2; OCN: Osteocalcin; ALP: Alkaline phosphatase; BSP: Bone Sialoprotein; OSX: Osterix; Spry1: Palmitate phosphoprotein Sprouty1; ACVR2B: Activin A receptor type 2B; OPN: Osteopontin; OCT4: Octamer-binding transcription factor-4; NANOG: Homeobox transcription factor nanog; ATF4: Activated transcription factor 4; CTNNB1: Catenin beta 1; TCF3: Transcriptional factor 3; Smurf1: Smad ubiquitin regulatory factor 1; Satb2: Special AT-rich sequence-binding protein 2; IL: Interleukin; CCL-5: Chemokines-5; OPG: Osteoprotegerin; TOB2: Transducer of ERBB2; COL1A1: Collagen type I alpha 1 chain; HDAC6: Histone deacetylase 6; Lin28A: Lin-28 homolog A; hnRNP I: Heterogeneous nuclear ribonucleoprotein I; DSPP: Dentin sialophosphoprotein; GSK3β: Glycogen synthase kinase 3β; ANCR: Anti-differentiation noncoding RNA; Notch2: Neurogenic locus notch homolog protein 2; ceRNA: Competing endogenous RNAs; EZH2: Enhancer of zeste homolog 2; H3K27me3: Histone H3 trimethylated at lysine 27; POIR: Osteogenesis impairment-related lncRNA of PDLSCs; FoxO1: Forkhead box O1; TCF4: Transcription factor 4; COL1: Collagen type I; PCAT1: Prostate cancer-associated ncRNA transcript-1; HIF1A‑AS1/2: HIF1A antisense RNA 1/2; HIF-1α: Hypoxia-inducible factor-1α; CDR1as: Antisense to the cerebellar degeneration-related protein 1 transcript; GDF5: Growth differentiation factor 5; MAPK: Mitogen-activated protein kinase; ACVR2B: Activin A receptor type 2B; SP7: Transcription Factor Sp7.