Dataset Information

MicroRNAs in oral fluids (saliva and gingival crevicular fluid) as biomarkers in orthodontics: systematic review and integrated bioinformatic analysis.

ABSTRACT:

Background

MicroRNAs (miRNAs) are non-coding short, single-stranded RNA molecules that may serve as biomarkers for various inflammatory and molecular mechanisms underlying bone and tissue remodeling consequent to orthodontic force application.

Methods

A thorough literature search in major databases was conducted in March 2021 to generate evidence for miRNAs in orthodontics, with prior PROSPERO registration. The initial search revealed 920 articles, subjected to strict selection criteria according to PRISMA, and resulted in final inclusion of four studies. Quality assessment by QUADAS-2 classified three studies as unclear risk-of-bias while the applicability was high. Further, bioinformatic analysis was performed to identify the target genes from the miRNA database (miRDB) and TargetScan databases and their protein-protein interaction pathways with the STRING analysis.

Results

Multiple miRNAs in gingival crevicular fluid (GCF) of orthodontic patients were seen, including miRNA-21, 27(a/b), 29(a/b/c), 34,146(a/b), 101, and 214 along with matrix metalloproteinases (MMPs)-1, 2, 3, 8, 9, 14 in one study. A statistically significant increase in expression of miRNA-29a/b/c,101, 21 from pre-treatment (before initiation of retraction) was seen to reach a peak at 4-6 weeks (wk) of retraction. On the contrary, miRNA-34a showed downregulation from the 1 day to 4 wk of retraction and also, negatively correlated with MMPs-2,9,14 levels at the same observation times. The distance of canine movement showed mild correlation with miRNA-27a/b, 214 at 2 wk of retraction. Bioinformatics revealed 1213 mutual target genes which were analyzed for inter-relational pathways using Cytoscape plugin, MCODE. Further, 894 prominent protein interactions were identified from the STRING database and SMAD4, IGF1, ADAMTS6, COL4A1, COL1A1, COL3A1, FGFR1, COL19A1, FBN1, COL5A1, MGAT4A, LTBP1, MSR1, COL11A1, and COL5A3 were recognized as the hub genes. Their interactions were able to isolate multiple miRNAs: hsa-miR-34a-5p, hsa-miR-29b-2-5p, hsa-miR-29b-3p, hsa-miR-34a-3p, hsa-miR-27a-5p, hsa-miR-29a-5p, hsa-miR-29b-1-5p, hsa-miR-29c-3p, hsa-miR-214-5p, hsa-miR-27a-3p, hsa-miR-29a-3p, hsamiR-146-5p, which were found promising as biomarkers for tooth movement.

Conclusions

Our results support using miRNAs as biomarkers in varied orthodontic study designs and for inter-relationships with pathological settings like periodontal disease, pre-malignancies, or conditions like obesity or metabolic irregularities, etc. The identified target genes and their protein interaction pathways can be used to propose precision therapies, focusing on ideal tooth movement with minimal iatrogenic side-effects.

SUBMITTER: Kapoor P

PROVIDER: S-EPMC8502526 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Understanding the pathophysiology of the coronavirus disease 2019 (COVID-19) infection remains a significant challenge of our times. The gingival crevicular fluid being representative of systemic status and having a proven track record of detecting viruses and biomarkers forms a logical basis for evaluating the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The study aimed to assess gingival crevicular fluid (GCF) for evidence of SARS-CoV-2 in 33 patients who were deemed to be COVID-19 positive upon nasopharyngeal sampling. An attempt was also made to comparatively evaluate it with saliva in terms of its sensitivity, as a diagnostic fluid for SARS-CoV-2. GCF and saliva samples were collected from 33 COVID-19-confirmed patients. Total RNA was extracted using NucliSENS easyMAG (bioMérieux) and eluted in the elution buffer. Envelope gene (E gene) of SARS-CoV-2 and human RNase P gene as internal control were detected in GCF samples by using the TRUPCR SARS-CoV-2 RT qPCR kit V-2.0 (I) in an Applied Biosystems 7500 real-time machine. A significant majority of both asymptomatic and mildly symptomatic patients exhibited the presence of the novel coronavirus in their GCF samples. Considering the presence of SARS-CoV-2 RNA in the nasopharyngeal swab sampling as gold standard, the sensitivity of GCF and saliva, respectively, was 63.64% (confidence interval [CI], 45.1% to 79.60%) and 64.52% (CI, 45.37% to 80.77%). GCF was found to be comparable to saliva in terms of its sensitivity to detect SARS-CoV-2. Saliva samples tested positive in 3 of the 12 patients whose GCF tested negative, and likewise GCF tested positive for 2 of the 11 patients whose saliva tested negative on real-time reverse transcription polymerase chain reaction. The results establish GCF as a possible mode of transmission of SARS-CoV-2, which is the first such report in the literature, and also provide the first quantifiable evidence pointing toward a link between the COVID-19 infection and oral health.