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.