Emerging Role of miRNAs in the Pathogenesis of Periodontitis

Mohammad      Taheri; Tayyebeh      Khoshbakht; Bashdar   Mahmud   Hussen; Sara   Tharwat   Abdullah; Soudeh      Ghafouri-Fard; Arezou      Sayad
doi:10.2174/1574888X17666220617103820
Abstract

MicroRNAs (miRNAs) have been found to participate in the pathogenesis of several immune-related conditions through the modulation of the expression of cytokine coding genes and other molecules that affect the activity of the immune system. Periodontitis is an example of these conditions associated with the dysregulation of several miRNAs. Several miRNAs such as let-7 family, miR-125, miR-378, miR-543, miR-302, miR-214, miR-200, miR-146, miR-142, miR-30 and miR-21 have been shown to be dysregulated in patients with periodontitis. miR-146 is the most assessed miRNA in these patients, which is up-regulated in most studies in patients with periodontitis. In the present review, we describe the impact of miRNAs dysregulation on the pathoetiology of periodontitis.
Keywords: MicroRNA, periodontitis, expression, biomarker, diagnose, pathogenesis.
[1]
Kornman KS. Mapping the pathogenesis of periodontitis: A new look. J Periodontol  2008; 79(8s) (Suppl.): 1560-8.
 [http://dx.doi.org/10.1902/jop.2008.080213] [PMID:  18673011]

[2]
Grossi SG, Zambon JJ, Ho AW, et al. Assessment of risk for periodontal disease. I. Risk indicators for attachment loss. J Periodontol  1994; 65(3): 260-7.
 [http://dx.doi.org/10.1902/jop.1994.65.3.260] [PMID:  8164120]

[3]
Ari G, Cherukuri S, Namasivayam A. Epigenetics and periodontitis: A contemporary review. J Clin Diagn Res  2016; 10(11): ZE07-9.
 [PMID:  28050521]

[4]
Zhang Y, Li Y. MicroRNAs in the regulation of immune response against infections. J Zhejiang Univ Sci B  2013; 14(1): 1-7.
 [http://dx.doi.org/10.1631/jzus.B1200292] [PMID:  23303626]

[5]
Bushati N, Cohen SM. microRNA Functions. Annu Rev Cell Dev Biol  2007; 23(1): 175-205.
 [http://dx.doi.org/10.1146/annurev.cellbio.23.090506.123406] [PMID:  17506695]

[6]
Gonçalves Fernandes J, Morford LA, Harrison PL, et al. Dysregulation of genes and microRNAs in localized aggressive periodontitis. J Clin Periodontol  2020; 47(11): 1317-25.
 [http://dx.doi.org/10.1111/jcpe.13361] [PMID:  32876337]

[7]
Asa’ad F, Garaicoa-Pazmiño C, Dahlin C, Larsson L. Expression of micrornas in periodontal and peri-implant diseases: A systematic review and meta-analysis. Int J Mol Sci  2020; 21(11): 4147.
 [http://dx.doi.org/10.3390/ijms21114147] [PMID:  32532036]

[8]
Venugopal P, Koshy T, Lavu V, et al. Differential expression of microRNAs let‐7a, miR‐125b, miR‐100, and miR‐21 and interaction with NF‐kB pathway genes in periodontitis pathogenesis. J Cell Physiol  2018; 233(8): 5877-84.
 [http://dx.doi.org/10.1002/jcp.26391] [PMID:  29226952]

[9]
Fu L, Li N, Ye Y, Ye X, Xiao T, Wu X, et al. MicroRNA Hsa-Let-7b regulates the osteogenic differentiation of human periodontal ligament stem cells by targeting CTHRC1. Stem Cells Int  2021; 5791181.
 [http://dx.doi.org/10.1155/2021/5791181]

[10]
Du W, Wang L, Liao Z, Wang J. Circ-0085289 alleviates the progression of periodontitis by regulating let-7f-5p/SOCS6 pathway. Inflammation  2021; 44(4): 1607-19.
 [http://dx.doi.org/10.1007/s10753-021-01445-8] [PMID:  33710445]

[11]
Shen Z, Wichnieski C, Carneiro E, Garlet GP, Letra A, Silva RM. Expression profiling and functional characterization of MicroRNAs in apical periodontitis. J Endod  2021; 47(2): 263-71.
 [http://dx.doi.org/10.1016/j.joen.2020.11.016] [PMID:  33245973]

[12]
Li J, Wang M, Song L, Wang X, Lai W, Jiang S. Lnc RNA MALAT 1 regulates inflammatory cytokine production in lipopolysaccharide‐stimulated human gingival fibroblasts through sponging miR‐20a and activating TLR 4 pathway. J Periodontal Res  2020; 55(2): 182-90.
 [http://dx.doi.org/10.1111/jre.12700] [PMID:  31552681]

[13]
Sun KT, Chen MYC, Tu MG, Wang IK, Chang SS, Li CY. MicroRNA-20a regulates autophagy related protein-ATG16L1 in hypoxia-induced osteoclast differentiation. Bone  2015; 73: 145-53.
 [http://dx.doi.org/10.1016/j.bone.2014.11.026] [PMID:  25485521]

[14]
Wang X, Wang Y. LncRNA DCST1‐AS1 inhibits PDLCs’ proliferation in periodontitis and may bind with miR‐21 precursor to upregulate PLAP‐1. J Periodontal Res  2021; 56(2): 256-64.
 [http://dx.doi.org/10.1111/jre.12809] [PMID:  33533513]

[15]
Wei F, Liu D, Feng C, et al. microRNA-21 mediates stretch-induced osteogenic differentiation in human periodontal ligament stem cells. Stem Cells Dev  2015; 24(3): 312-9.
 [http://dx.doi.org/10.1089/scd.2014.0191] [PMID:  25203845]

[16]
Zhou W, Su L, Duan X, et al. MicroRNA-21 down-regulates inflammation and inhibits periodontitis. Mol Immunol  2018; 101: 608-14.
 [http://dx.doi.org/10.1016/j.molimm.2018.05.008] [PMID:  29884447]

[17]
Lee NH, Lee E, Kim YS, Kim WK, Lee YK, Kim SH. Differential expression of microRNAs in the saliva of patients with aggressive periodontitis: A pilot study of potential biomarkers for aggressive periodontitis. J Periodontal Implant Sci  2020; 50(5): 281-90.
 [http://dx.doi.org/10.5051/jpis.2000120006] [PMID:  33124206]

[18]
Zhang Z, Shuai Y, Zhou F, et al. PDLSCs regulate angiogenesis of periodontal ligaments via VEGF transferred by exosomes in periodontitis. Int J Med Sci  2020; 17(5): 558-67.
 [http://dx.doi.org/10.7150/ijms.40918] [PMID:  32210705]

[19]
Coêlho MC, Queiroz IC. viana JMC. Aquino SGd, Persuhn DC, Oliveira NFPd. miR-9-1 gene methylation and DNMT3B (rs2424913) polymorphism may contribute to periodontitis. J Appl Oral Sci  2020; 28: e20190583.

[20]
Silva-Sousa AC, Mazzi-Chaves JF, Freitas JV, et al. Association between estrogen, vitamin D and microRNA17 gene polymorphisms and periapical lesions. Braz Dent J  2020; 31(1): 19-24.
 [http://dx.doi.org/10.1590/0103-644020200] [PMID:  32159700]

[21]
Li L, Liu W, Wang H, et al. Mutual inhibition between HDAC9 and miR-17 regulates osteogenesis of human periodontal ligament stem cells in inflammatory conditions. Cell Death Dis  2018; 9(5): 480.
 [http://dx.doi.org/10.1038/s41419-018-0480-6] [PMID:  29691366]

[22]
Chen N, Sui BD, Hu CH, et al. microRNA-21 contributes to orthodontic tooth movement. J Dent Res  2016; 95(12): 1425-33.
 [http://dx.doi.org/10.1177/0022034516657043] [PMID:  27422860]

[23]
Zheng M, Guo J. Nicotinamide‐induced silencing of SIRT1 by miR‐22‐3p increases periodontal ligament stem cell proliferation and differentiation. Cell Biol Int  2020; 44(3): 764-72.
 [http://dx.doi.org/10.1002/cbin.11271] [PMID:  31769563]

[24]
Zhang Y, Li S, Yuan S, Zhang H, Liu J. MicroRNA-23a inhibits osteogenesis of periodontal mesenchymal stem cells by targeting bone morphogenetic protein signaling. Arch Oral Biol  2019; 102: 93-100.
 [http://dx.doi.org/10.1016/j.archoralbio.2019.04.001] [PMID:  30981077]

[25]
Li Z, Sun Y, Cao S, Zhang J, Wei J. Downregulation of miR‐24‐3p promotes osteogenic differentiation of human periodontal ligament stem cells by targeting SMAD family member 5. J Cell Physiol  2019; 234(5): 7411-9.
 [http://dx.doi.org/10.1002/jcp.27499] [PMID:  30378100]

[26]
Zhang K, Geng Y, Wang S, Huo L. MicroRNA-26a-5p targets Wnt5a to regulate osteogenic differentiation of human periodontal ligament stem cell from inflammatory microenvironment  Zhonghua kou qiang yi xue za zhi  2019; 54(10): 662-9.

[27]
Liu Y, Liu C, Zhang A, et al. Down-regulation of long non-coding RNA MEG3 suppresses osteogenic differentiation of periodontal ligament stem cells (PDLSCs) through miR-27a-3p/IGF1 axis in periodontitis. Aging (Albany NY)  2019; 11(15): 5334-50.
 [http://dx.doi.org/10.18632/aging.102105] [PMID:  31398715]

[28]
Liu X, Yang B, Zhang Y, et al. miR-30a-5p inhibits osteogenesis and promotes periodontitis by targeting Runx2. BMC Oral Health  2021; 21(1): 513.
 [http://dx.doi.org/10.1186/s12903-021-01882-9] [PMID:  34635105]

[29]
Wu L, Yang K, Gui Y, Wang X. Nicotine-upregulated miR-30a arrests cell cycle in G1 phase by directly targeting CCNE2 in human periodontal ligament cells. Biochem Cell Biol  2020; 98(3): 354-61.
 [http://dx.doi.org/10.1139/bcb-2019-0156] [PMID:  31689122]

[30]
Wang L, He Y, Ning W. Role of enhancer of zeste homolog 2 in osteoclast formation and periodontitis development by downregulating microRNA‐101‐regulated VCAM‐1. J Tissue Eng Regen Med  2021; 15(6): 534-45.
 [http://dx.doi.org/10.1002/term.3187] [PMID:  33686766]

[31]
Liu M, Liu Q, Fan S, et al. LncRNA LTSCCAT promotes tongue squamous cell carcinoma metastasis via targeting the miR-103a-2-5p/SMYD3/TWIST1 axis. Cell Death Dis  2021; 12(2): 144.
 [http://dx.doi.org/10.1038/s41419-021-03415-2] [PMID:  33542221]

[32]
He F, Zhou Y, Wang X, et al. Functional polymorphisms of ctla4 associated with aggressive periodontitis in the chinese han population. Cell Physiol Biochem  2018; 50(3): 1178-85.
 [http://dx.doi.org/10.1159/000494544] [PMID:  30355938]

[33]
Jia B, Qiu X, Chen J, et al. A feed‐forward regulatory network lncPCAT1/miR‐106a‐5p/E2F5 regulates the osteogenic differentiation of periodontal ligament stem cells. J Cell Physiol  2019; 234(11): 19523-38.
 [http://dx.doi.org/10.1002/jcp.28550] [PMID:  30997692]

[34]
He W, Zhang N, Lin Z. MicroRNA-125a-5p modulates macrophage polarization by targeting E26 transformation-specific variant 6 gene during orthodontic tooth movement. Arch Oral Biol  2021; 124: 105060.
 [http://dx.doi.org/10.1016/j.archoralbio.2021.105060] [PMID: 33524878]

[35]
Dong Y, Li P, Ni Y, Zhao J, Liu Z. Decreased microRNA-125a-3p contributes to upregulation of p38 MAPK in rat trigeminal ganglions with orofacial inflammatory pain. PLoS One  2014; 9(11): e111594.
 [http://dx.doi.org/10.1371/journal.pone.0111594] [PMID:  25380251]

[36]
Wang Y, Lv F, Huang L, et al. Human amnion-derived mesenchymal stem cells promote osteogenic differentiation of lipopolysaccharide-induced human bone marrow mesenchymal stem cells via ANRIL/miR-125a/APC axis. Stem Cell Res Ther  2021; 12(1): 35.
 [http://dx.doi.org/10.1186/s13287-020-02105-8] [PMID:  33413674]

[37]
Venugopal P, Lavu V, Rao SR, Venkatesan V. Association of microRNA-125a and microRNA-499a polymorphisms in chronic periodontitis in a sample south Indian population: A hospital-based genetic association study. Gene  2017; 631: 10-5.
 [http://dx.doi.org/10.1016/j.gene.2017.07.053] [PMID:  28732738]

[38]
Xue N, Qi L, Zhang G, Zhang Y. miRNA-125b regulates osteogenic differentiation of periodontal ligament cells through NKIRAS2/NF-κB pathway. Cell Physiol Biochem  2018; 48(4): 1771-81.
 [http://dx.doi.org/10.1159/000492350] [PMID:  30078007]

[39]
Mu Y, Deng J, Li J, Song L, Jiang S. Regulatory effect of microRNA-126 on macrophage proliferation caused by high glucose stimulation. Zhonghua kou Qiang yi xue za zhi= Zhonghua Kouqiang Yixue Zazhi= Chinese Journal of Stomatology  2020; 55(12): 969-75.

[40]
Wu Y, Song LT, Li JS, Zhu DW, Jiang SY, Deng JY. MicroRNA‐126 regulates inflammatory cytokine secretion in human gingival fibroblasts under high glucose via targeting tumor necrosis factor receptor associated factor 6. J Periodontol  2017; 88(11): e179-87.
 [http://dx.doi.org/10.1902/jop.2017.170091] [PMID:  28598282]

[41]
Mahendra J, Mahendra L, Fageeh HN, et al. miRNA-146a and miRNA-126 as potential biomarkers in patients with coronary artery disease and generalized periodontitis. Materials (Basel)  2021; 14(16): 4692.
 [http://dx.doi.org/10.3390/ma14164692] [PMID:  34443215]

[42]
Na HS, Park MH, Song YR, et al. Elevated microRNA‐128 in periodontitis mitigates tumor necrosis factor‐α response via p38 signaling pathway in macrophages. J Periodontol  2016; 87(9): e173-82.
 [http://dx.doi.org/10.1902/jop.2016.160033] [PMID:  27240473]

[43]
Yu M, Chi C. lncRNA FGD5-AS1 and miR-130a Can Be Used for Prognosis Analysis of Patients with Chronic Periodontitis. BioMed Res Int 2021.

[44]
Xu Y, Ren C, Zhao X, Wang W, Zhang N. microRNA-132 inhibits osteogenic differentiation of periodontal ligament stem cells via GDF5 and the NF-κB signaling pathway. Pathol Res Pract  2019; 215(12): 152722.
 [http://dx.doi.org/10.1016/j.prp.2019.152722] [PMID:  31718857]

[45]
Han Y, Wang F, Shao L, Huang P, Xu Y. LncRNA TUG1 mediates lipopolysaccharide-induced proliferative inhibition and apoptosis of human periodontal ligament cells by sponging miR-132. Acta Biochim Biophys Sin (Shanghai)  2019; 51(12): gmz125.
 [http://dx.doi.org/10.1093/abbs/gmz125] [PMID:  31735958]

[46]
Han P, Bartold PM, Salomon C, Ivanovski S. Salivary small extracellular vesicles associated miRNAs in periodontal status—A pilot study. Int J Mol Sci  2020; 21(8): 2809.
 [http://dx.doi.org/10.3390/ijms21082809] [PMID:  32316600]

[47]
Rovas A, Puriene A, Snipaitiene K, Punceviciene E, Buragaite-Staponkiene B, Matuleviciute R, et al. Gingival crevicular fluid microRNA associations with periodontitis. J Oral Sci  2021; 64(1): 11-6.
 [PMID:  34690249]

[48]
Zhou X, Luan X, Chen Z, et al. MicroRNA-138 inhibits periodontal progenitor differentiation under inflammatory conditions. J Dent Res  2016; 95(2): 230-7.
 [http://dx.doi.org/10.1177/0022034515613043] [PMID:  26518300]

[49]
Li S, Song Z, Dong J, Shu R. microRNA-142 is upregulated by tumor necrosis factor-alpha and triggers apoptosis in human gingival epithelial cells by repressing BACH2 expression. Am J Transl Res  2017; 9(1): 175-83.
 [PMID:  28123644]

[50]
Chen H, Lan Z, Li Q, Li Y. Abnormal expression of long noncoding RNA FGD5-AS1 affects the development of periodontitis through regulating miR-142-3p/SOCS6/NF-κB pathway. Artif Cells Nanomed Biotechnol  2019; 47(1): 2098-106.
 [http://dx.doi.org/10.1080/21691401.2019.1620256] [PMID: 31144533]

[51]
Dong Y, Feng S, Dong F. Maternally-Expressed Gene 3 (MEG3)/miR-143-3p Regulates Injury to Periodontal Ligament Cells by Mediating the AKT/Inhibitory κB Kinase (IKK) Pathway. Med Sci Monit  2020; 26: e922486-1.
 [http://dx.doi.org/10.12659/MSM.922486] [PMID:  32520926]

[52]
Nisha KJ, Janam P, Harshakumar K. Identification of a novel salivary biomarker miR‐143‐3p for periodontal diagnosis: A proof of concept study. J Periodontol  2019; 90(10): 1149-59.
 [http://dx.doi.org/10.1002/JPER.18-0729] [PMID:  31021403]

[53]
Li J, Wang R, Ge Y, Chen D, Wu B, Fang F. Assessment of microRNA‐144‐5p and its putative targets in inflamed gingiva from chronic periodontitis patients. J Periodontal Res  2019; 54(3): 266-77.
 [http://dx.doi.org/10.1111/jre.12627] [PMID:  30450635]

[54]
Ghotloo S, Motedayyen H, Amani D, Saffari M, Sattari M. Assessment of microRNA-146a in generalized aggressive periodontitis and its association with disease severity. J Periodontal Res  2019; 54(1): 27-32.
 [http://dx.doi.org/10.1111/jre.12538] [PMID:  30328616]

[55]
Zhao S, Cheng Y, Kim JG. microRNA‐146a downregulates IL‐17 and IL‐35 and inhibits proliferation of human periodontal ligament stem cells. J Cell Biochem  2019; 120(8): 13861-6.
 [http://dx.doi.org/10.1002/jcb.28659] [PMID:  30989711]

[56]
Lina S, Lihong Q, Di Y, Bo Y, Xiaolin L, Jing M. microRNA‐146a and Hey2 form a mutual negative feedback loop to regulate the inflammatory response in chronic apical periodontitis. J Cell Biochem  2019; 120(1): 645-57.
 [http://dx.doi.org/10.1002/jcb.27422] [PMID:  30125982]

[57]
Wang Y, Wei Z, Xia T, Shi B. MicroRNA-146a downregulates interleukin-13 and inhibits the proliferation of human periodontal ligament stem cells. Arch Oral Biol  2021; 129: 105165.
 [http://dx.doi.org/10.1016/j.archoralbio.2021.105165] [PMID: 34146927]

[58]
Tang L, Li X, Bai Y, Wang P, Zhao Y. MicroRNA‐146a negatively regulates the inflammatory response to Porphyromonas gingivalis in human periodontal ligament fibroblasts via TRAF6/p38 pathway. J Periodontol  2019; 90(4): 391-9.
 [http://dx.doi.org/10.1002/JPER.18-0190] [PMID:  30378773]

[59]
Sattari M, Taheri RA. ArefNezhad R, Motedayyen H. The expression levels of MicroRNA-146a, RANKL and OPG after non-surgical periodontal treatment. BMC Oral Health  2021; 21(1): 523.
 [http://dx.doi.org/10.1186/s12903-021-01883-8] [PMID:  33388028]

[60]
Yagnik K, Mahendra J, Kurian VM. The Periodontal‐Cardiovascular alliance: Evaluation of miRNA‐146a in subgingival plaque samples of chronic periodontitis patients with and without coronary heart disease. J Investig Clin Dent  2019; 10(4): e12442.
 [http://dx.doi.org/10.1111/jicd.12442] [PMID:  31338994]

[61]
Bagavad Gita J, George AV, Pavithra N, Chandrasekaran SC, Latchumanadhas K, Gnanamani A. Dysregulation of miR-146a by periodontal pathogens: A risk for acute coronary syndrome. J Periodontol  2019; 90(7): 756-65.
 [http://dx.doi.org/10.1002/JPER.18-0466] [PMID:  30618100]

[62]
Gao Y, Hao C. Expression of miR-146a in saliva of chronic periodontitis patients and its influence on gingival crevicular inflammation and MMP-8/TIMP-1 levels. Shanghai Kou Qiang Yi Xue  2018; 27(3): 309-12.

[63]
Jiang S, Hu Y, Deng S, et al. miR-146a regulates inflammatory cytokine production in Porphyromonas gingivalis lipopolysaccharide-stimulated B cells by targeting IRAK1 but not TRAF6. Biochim Biophys Acta Mol Basis Dis  2018; 1864(3): 925-33.
 [http://dx.doi.org/10.1016/j.bbadis.2017.12.035] [PMID:  29288795]

[64]
Motedayyen H, Ghotloo S, Saffari M, Sattari M, Amid R. Evaluation of microRNA‐146a and its targets in gingival tissues of patients with chronic periodontitis. J Periodontol  2015; 86(12): 1380-5.
 [http://dx.doi.org/10.1902/jop.2015.150319] [PMID:  26313020]

[65]
Xie YF, Shu R, Jiang SY, Liu DL, Ni J, Zhang XL. MicroRNA-146 inhibits pro-inflammatory cytokine secretion through IL-1 receptor-associated kinase 1 in human gingival fibroblasts. J Inflamm (Lond)  2013; 10(1): 20.
 [http://dx.doi.org/10.1186/1476-9255-10-20] [PMID:  23680172]

[66]
Sanada T, Sano T, Sotomaru Y, et al. Anti-inflammatory effects of miRNA-146a induced in adipose and periodontal tissues. Biochem Biophys Rep  2020; 22: 100757.
 [http://dx.doi.org/10.1016/j.bbrep.2020.100757] [PMID:  32346618]

[67]
Xu R, Zeng G, Wang S, et al. Periodontitis promotes the diabetic development of obese rat via miR-147 induced classical macrophage activation. Biomed Pharmacother  2016; 83: 892-7.
 [http://dx.doi.org/10.1016/j.biopha.2016.07.030] [PMID:  27518498]

[68]
Bao L, Zhang X, Xu Y, et al. Dysfunction of mir-148a-nrp1 functional axis suppresses osteogenic differentiation of periodontal ligament stem cells under inflammatory microenvironment. Cell Reprogram  2019; 21(6): 314-22.
 [http://dx.doi.org/10.1089/cell.2019.0026] [PMID:  31809209]

[69]
Wu D, Ma L. Downregulating microRNA-152-3p promotes the viability and osteogenic differentiation of periodontal ligament stem cells via targeting integrin alpha 5. Arch Oral Biol  2020; 120: 104930.
 [http://dx.doi.org/10.1016/j.archoralbio.2020.104930] [PMID:  33059275]

[70]
Jiang H, Jia P. MiR‐153‐3p inhibits osteogenic differentiation of periodontal ligament stem cells through KDM6A‐induced demethylation of H3K27me3. J Periodontal Res  2021; 56(2): 379-87.
 [http://dx.doi.org/10.1111/jre.12830] [PMID:  33368310]

[71]
Mahendra J, Mahendra L, Mugri MH, et al. Role of periodontal bacteria, viruses, and placental mir155 in chronic periodontitis and preeclampsia—a genetic microbiological study. Curr Issues Mol Biol  2021; 43(2): 831-44.
 [http://dx.doi.org/10.3390/cimb43020060] [PMID:  34449559]

[72]
Wang X, Sun H, Liao H, et al. MicroRNA-155-3p mediates TNF-α-inhibited cementoblast differentiation. J Dent Res  2017; 96(12): 1430-7.
 [http://dx.doi.org/10.1177/0022034517718790] [PMID:  28692806]

[73]
Zheng Y, Dong C, Yang J, et al. Exosomal microRNA‐155‐5p from PDLSCs regulated Th17/Treg balance by targeting sirtuin‐1 in chronic periodontitis. J Cell Physiol  2019; 234(11): 20662-74.
 [http://dx.doi.org/10.1002/jcp.28671] [PMID:  31016751]

[74]
Roganović JR. microRNA‐146a and ‐155, upregulated by periodontitis and type 2 diabetes in oral fluids, are predicted to regulate SARS‐CoV‐2 oral receptor genes. J Periodontol  2021; 92(7): 35-43.
 [http://dx.doi.org/10.1002/JPER.20-0623] [PMID:  33336412]

[75]
Radović N, Nikolić Jakoba N, Petrović N, Milosavljević A, Brković B, Roganović J. MicroRNA-146a and microRNA-155 as novel crevicular fluid biomarkers for periodontitis in non-diabetic and type 2 diabetic patients. J Clin Periodontol  2018; 45(6): 663-71.
 [http://dx.doi.org/10.1111/jcpe.12888] [PMID:  29517812]

[76]
Al-Rawi NH, Al-Marzooq F, Al-Nuaimi AS, Hachim MY, Hamoudi R. Salivary microRNA 155, 146a/b and 203: A pilot study for potentially non-invasive diagnostic biomarkers of periodontitis and diabetes mellitus. PLoS One  2020; 15(8): e0237004.
 [http://dx.doi.org/10.1371/journal.pone.0237004] [PMID:  32756589]

[77]
Wu P, Feng J, Wang W. Expression of miR-155 and miR-146a in the saliva of patients with periodontitis and its clinical value. Am J Transl Res  2021; 13(6): 6670-7.
 [PMID:  34306411]

[78]
Molteni M, Bosi A, Rossetti C. The effect of cyanobacterial LPS antagonist (CyP) on cytokines and micro-RNA expression Induced by Porphyromonas gingivalis LPS. Toxins (Basel)  2018; 10(7): 290.
 [http://dx.doi.org/10.3390/toxins10070290] [PMID:  30012943]

[79]
Wang X, Sun H, Liu H, et al. MicroRNA‐181b‐5p modulates tumor necrosis factor‐α‐induced inflammatory responses by targeting interleukin‐6 in cementoblasts. J Cell Physiol  2019; 234(12): 22719-30.
 [http://dx.doi.org/10.1002/jcp.28837] [PMID:  31131439]

[80]
Lv P, Gao P, Tian G, et al. Osteocyte-derived exosomes induced by mechanical strain promote human periodontal ligament stem cell proliferation and osteogenic differentiation via the miR-181b-5p/PTEN/AKT signaling pathway. Stem Cell Res Ther  2020; 11(1): 295.
 [http://dx.doi.org/10.1186/s13287-020-01815-3] [PMID:  32680565]

[81]
Wang L, Wu F, Song Y, Li X, Wu Q, Duan Y, et al. Long noncoding RNA related to periodontitis interacts with miR-182 to upregulate osteogenic differentiation in periodontal mesenchymal stem cells of periodontitis patients. Cell Death Dis  2016; 7(8): e2327.
 [http://dx.doi.org/10.1038/cddis.2016.125]

[82]
Rovas A, Puriene A, Snipaitiene K, et al. Analysis of periodontitis-associated miRNAs in gingival tissue, gingival crevicular fluid, saliva and blood plasma. Arch Oral Biol  2021; 126: 105125.
 [http://dx.doi.org/10.1016/j.archoralbio.2021.105125] [PMID: 33862403]

[83]
Venugopal P, Lavu V. RangaRao S, Venkatesan V. RangaRao S, Venkatesan V. Evaluation of a panel of single-nucleotide polymorphisms in miR-146a and miR-196a2 genomic regions in patients with chronic periodontitis. Genet Test Mol Biomarkers  2017; 21(4): 228-35.
 [http://dx.doi.org/10.1089/gtmb.2016.0358] [PMID:  28384038]

[84]
Li M, Wei L, Zhou W, He Z, Ran S, Liang J. miR-200a contributes to the migration of BMSCs induced by the secretions of E. faecalis via FOXJ1/NFκB/MMPs axis. Stem Cell Res Ther  2020; 11(1): 317.
 [http://dx.doi.org/10.1186/s13287-020-01833-1] [PMID:  31900237]

[85]
Akkouch A, Zhu M, Romero-Bustillos M, et al. MicroRNA-200c attenuates periodontitis by modulating proinflammatory and osteoclastogenic mediators. Stem Cells Dev  2019; 28(15): 1026-36.
 [http://dx.doi.org/10.1089/scd.2019.0027] [PMID:  31017046]

[86]
Krongbaramee T, Zhu M, Qian Q, et al. Plasmid encoding microRNA-200c ameliorates periodontitis and systemic inflammation in obese mice. Mol Ther Nucleic Acids  2021; 23: 1204-16.
 [http://dx.doi.org/10.1016/j.omtn.2021.01.030] [PMID:  33664998]

[87]
Hong L, Sharp T, Khorsand B, et al. MicroRNA-200c represses IL-6, IL-8, and CCL-5 expression and enhances osteogenic differentiation. PLoS One  2016; 11(8): e0160915.
 [http://dx.doi.org/10.1371/journal.pone.0160915] [PMID:  27529418]

[88]
Matsui S, Zhou L, Nakayama Y, et al. MiR-200b attenuates IL-6 production through IKKβ and ZEB1 in human gingival fibroblasts. Inflamm Res  2018; 67(11-12): 965-73.
 [http://dx.doi.org/10.1007/s00011-018-1192-1] [PMID:  30306207]

[89]
Kalea AZ, Hoteit R, Suvan J, et al. Upregulation of gingival tissue miR-200b in obese periodontitis subjects. J Dent Res  2015; 94(3-suppl): 59S-69S.
 [http://dx.doi.org/10.1177/0022034514568197] [PMID: 25630869]

[90]
Elazazy O, Amr K, Abd El Fattah A, Abouzaid M. Evaluation of serum and gingival crevicular fluid microRNA-223, microRNA-203 and microRNA-200b expression in chronic periodontitis patients with and without diabetes type 2. Arch Oral Biol  2021; 121: 104949.
 [http://dx.doi.org/10.1016/j.archoralbio.2020.104949] [PMID: 33157494]

[91]
Li J, Li L, Wang X, Xiao L. Porphyromonas gingivalis inhibition of MicroRNA-205-5p expression modulates proinflammatory cytokines in gingival epithelial cells. Biochem Genet  2020; 58(4): 566-79.
 [http://dx.doi.org/10.1007/s10528-020-09957-y] [PMID:  32303947]

[92]
Tomofuji T, Yoneda T, Machida T, et al. MicroRNAs as serum biomarkers for periodontitis. J Clin Periodontol  2016; 43(5): 418-25.
 [http://dx.doi.org/10.1111/jcpe.12536] [PMID:  26910654]

[93]
Pizzicannella J, Cavalcanti M, Trubiani O, Diomede F. MicroRNA 210 mediates VEGF upregulation in human periodontal ligament stem cells cultured on 3Dhydroxyapatite ceramic scaffold. Int J Mol Sci  2018; 19(12): 3916.
 [http://dx.doi.org/10.3390/ijms19123916] [PMID:  30563289]

[94]
Hua B, Xiang J, Guo L, Lu D. MicroRNA-212-5p regulates the inflammatory response of periodontal ligament cells by targeting myeloid differentiation factor 88. Arch Oral Biol  2020; 118: 104831.
 [http://dx.doi.org/10.1016/j.archoralbio.2020.104831] [PMID:  32707140]

[95]
Feng Y, Wan P, Yin L. Long noncoding RNA X-inactive specific transcript (XIST) promotes osteogenic differentiation of periodontal ligament stem cells by sponging microRNA-214-3p. Med Sci Monit  2020; 26: e918932-1.
 [http://dx.doi.org/10.12659/MSM.918932] [PMID:  32057034]

[96]
Ou L, Sun T, Cheng Y, et al. MicroRNA‐214 contributes to regulation of necroptosis via targeting ATF4 in diabetes‐associated periodontitis. J Cell Biochem  2019; 120(9): 14791-803.
 [http://dx.doi.org/10.1002/jcb.28740] [PMID:  31090954]

[97]
Yao S, Zhao W, Ou Q, Liang L, Lin X, Wang Y. MicroRNA-214 suppresses osteogenic differentiation of human periodontal ligament stem cells by targeting ATF4. Stem Cells Int 2017.
 [http://dx.doi.org/10.1155/2017/3028647]

[98]
Cao F, Zhan J, Chen X, Zhang K, Lai R, Feng Z. miR-214 promotes periodontal ligament stem cell osteoblastic differentiation by modulating Wnt/β-catenin signaling. Mol Med Rep  2017; 16(6): 9301-8.
 [http://dx.doi.org/10.3892/mmr.2017.7821] [PMID:  29152645]

[99]
Guo J, Zeng X, Miao J, et al. Expression of concern: MiRNA‐218 regulates osteoclast differentiation and inflammation response in periodontitis rats through Mmp9. Cell Microbiol  2019; 21(4): e12979.
 [http://dx.doi.org/10.1111/cmi.12979] [PMID:  30444938]

[100]
Wu D, Yin L, Sun D, et al. Long noncoding RNA TUG1 promotes osteogenic differentiation of human periodontal ligament stem cell through sponging microRNA-222-3p to negatively regulate Smad2/7. Arch Oral Biol  2020; 117: 104814.
 [http://dx.doi.org/10.1016/j.archoralbio.2020.104814] [PMID: 32574885]

[101]
Zhang S, Li C, Liu J, et al. Fusobacterium nucleatum promotes epithelial‐mesenchymal transiton through regulation of the lncRNA MIR4435‐2HG/miR‐296‐5p/Akt2/SNAI1 signaling pathway. FEBS J  2020; 287(18): 4032-47.
 [http://dx.doi.org/10.1111/febs.15233] [PMID:  31997506]

[102]
Irwandi RA, Khonsuphap P, Limlawan P, Vacharaksa A. miR‐302a‐3p regulates RANKL expression in human mandibular osteoblast‐like cells. J Cell Biochem  2018; 119(6): 4372-81.
 [http://dx.doi.org/10.1002/jcb.26456] [PMID:  29058810]

[103]
Duan Y, An W, Wu Y, Wang J. Tetramethylpyrazine reduces inflammation levels and the apoptosis of LPS stimulated human periodontal ligament cells via the downregulation of miR 302b. Int J Mol Med  2020; 45(6): 1918-26.
 [http://dx.doi.org/10.3892/ijmm.2020.4554] [PMID:  32236610]

[104]
Wang Y, Li Y, Shao P, Wang L, Bao X, Hu M. IL1β inhibits differentiation of cementoblasts via microRNA‐325‐3p. J Cell Biochem  2020; 121(3): 2606-17.
 [http://dx.doi.org/10.1002/jcb.29482] [PMID:  31680324]

[105]
Wang Z, Wang D, Guo S, Zhuo Q, Jiang D, Yu Z. Long noncoding RNA distal-less homeobox 2 antisense 1 restrains inflammatory response and apoptosis of periodontal ligament cells by binding with microRNA-330-3p to regulate Ro60, Y RNA binding protein. Arch Oral Biol  2022; 133: 105298.
 [http://dx.doi.org/10.1016/j.archoralbio.2021.105298] [PMID: 34752991]

[106]
Lian J, Wu X, Liu Y, et al. Potential roles of miR‐335‐5p on pathogenesis of experimental periodontitis. J Periodontal Res  2020; 55(2): 191-8.
 [http://dx.doi.org/10.1111/jre.12701] [PMID:  31541471]

[107]
Yue J, Wang P, Hong Q, et al. MicroRNA-335-5p plays dual roles in periapical lesions by complex regulation pathways. J Endod  2017; 43(8): 1323-8.
 [http://dx.doi.org/10.1016/j.joen.2017.03.018] [PMID:  28578884]

[108]
Mueller R, Bajric D, Keceli HG, et al. hsa‐miR‐374b‐5p regulates expression of the gene U2AF homology motif (UHM) kinase 1. J Periodontal Res  2021; 56(6): 1028-36.
 [http://dx.doi.org/10.1111/jre.12913] [PMID:  34160076]

[109]
Wang J, Du C, Xu L. Circ-0081572 inhibits the progression of periodontitis through regulating the miR-378h/RORA axis. Arch Oral Biol  2021; 124: 105053.
 [http://dx.doi.org/10.1016/j.archoralbio.2021.105053] [PMID: 33524877]

[110]
Zhou H, Li X, Wu RX, et al. Periodontitis‐compromised dental pulp stem cells secrete extracellular vesicles carrying miRNA‐378a promote local angiogenesis by targeting Sufu to activate the Hedgehog/Gli1 signalling. Cell Prolif  2021; 54(5): e13026.
 [http://dx.doi.org/10.1111/cpr.13026] [PMID:  33759282]

[111]
Ma L, Wu D. MicroRNA-383-5p regulates osteogenic differentiation of human periodontal ligament stem cells by targeting histone deacetylase 9. Arch Oral Biol  2021; 129: 105166.
 [http://dx.doi.org/10.1016/j.archoralbio.2021.105166] [PMID: 34118749]

[112]
Huang N, Li C, Sun W, Wu J, Xiao F. Long non‐coding RNA TUG1 participates in LPS‐induced periodontitis by regulating miR‐498/RORA pathway. Oral Dis  2021; 27(3): 600-10.
 [http://dx.doi.org/10.1111/odi.13590] [PMID:  32762066]

[113]
Kadkhodazadeh M, Jafari AR, Amid R, et al. MiR146a and MiR499 gene polymorphisms in Iranian periodontitis and peri-implantitis patients. J Long Term Eff Med Implants  2013; 23(1): 9-16.
 [http://dx.doi.org/10.1615/JLongTermEffMedImplants.2013007073] [PMID:  24266439]

[114]
Zhou M, Hu H, Han Y, et al. Long non‐coding RNA 01126 promotes periodontitis pathogenesis of human periodontal ligament cells via miR‐518a‐5p/HIF‐1α/MAPK pathway. Cell Prolif  2021; 54(1): e12957.
 [http://dx.doi.org/10.1111/cpr.12957] [PMID:  33231338]

[115]
Li W, Wang J, Hao W, Yu C. MicroRNA-543-3p down-regulates inflammation and inhibits periodontitis through KLF6. Biosci Rep  2021; 41(5): BSR20210138.
 [http://dx.doi.org/10.1042/BSR20210138] [PMID:  33955459]

[116]
Ge Y, Li J, Hao Y, et al. MicroRNA-543 functions as an osteogenesis promoter in human periodontal ligament-derived stem cells by inhibiting transducer of ERBB2, 2. J Periodontal Res  2018; 53(5): 832-41.
 [http://dx.doi.org/10.1111/jre.12572] [PMID:  29851072]

[117]
Li J, Xie R. Circular RNA expression profile in gingival tissues identifies circ-0062491 and circ-0095812 as potential treatment targets. J Cell Biochem  2019; 120(9): 14867-74.
 [http://dx.doi.org/10.1002/jcb.28748] [PMID:  31021476]

[118]
Shao Q, Liu S, Zou C, Ai Y. Effect of LSD1 on osteogenic differentiation of human periodontal ligament stem cells in periodontitis 2021. Oral Dis 2021; odi.14066.
 [http://dx.doi.org/10.1111/odi.14066] [PMID: 34739163]

[119]
Yang J, Zhou J, Cui B, Yu T. Evaluation of hypoxia on the expression of miR-646/IGF-1 signaling in human periodontal ligament cells (hPDLCs). Med Sci Monit  2018; 24: 5282-91.
 [http://dx.doi.org/10.12659/MSM.910163] [PMID:  30058629]

[120]
Peng W, Deng W, Zhang J, Pei G, Rong Q, Zhu S. Long noncoding RNA ANCR suppresses bone formation of periodontal ligament stem cells via sponging miRNA-758. Biochem Biophys Res Commun  2018; 503(2): 815-21.
 [http://dx.doi.org/10.1016/j.bbrc.2018.06.081] [PMID:  29913147]

[121]
Chen Q, Cao M, Ge H. Knockdown of MALAT1 inhibits the progression of chronic periodontitis via targeting miR-769-5p/HIF3A axis. BioMed Res Int 2021.

[122]
Huang Y, Han Y, Guo R, et al. Long non-coding RNA FER1L4 promotes osteogenic differentiation of human periodontal ligament stromal cells via miR-874-3p and vascular endothelial growth factor A. Stem Cell Res Ther  2020; 11(1): 5.
 [http://dx.doi.org/10.1186/s13287-019-1519-z] [PMID:  31900200]

[123]
Du Y, Qi Y, Chen H, Shen G. The expression and clinical significance of miR-1226 in patients with periodontitis. BMC Oral Health  2021; 21(1): 487.
 [http://dx.doi.org/10.1186/s12903-021-01855-y] [PMID:  34592963]

[124]
Micó-Martínez P, García-Giménez J, Seco-Cervera M, et al. miR-1226 detection in GCF as potential biomarker of chronic periodontitis: A pilot study. Med Oral Patol Oral Cir Bucal  2018; 23(3): 0.
 [http://dx.doi.org/10.4317/medoral.22329] [PMID: 29680855]

[125]
Liu Y, Yang J, Sun W. Upregulation of IL-10 expression inhibits the proliferation of human periodontal ligament stem cells. Braz Oral Res  2020; 34: e030.
 [http://dx.doi.org/10.1590/1807-3107bor-2020.vol34.0030] [PMID:  32236319]
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DOI https://dx.doi.org/10.2174/1574888X17666220617103820	Print ISSN 1574-888X
Publisher Name Bentham Science Publisher	Online ISSN 2212-3946
Current Stem Cell Research & Therapy

Emerging Role of miRNAs in the Pathogenesis of Periodontitis

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