Expression of MicroRNAs in Periodontal and Peri-Implant Diseases: A Systematic Review and Meta-Analysis

Abstract

Aim: The purpose of this review was to evaluate the expression patterns of miRNAs in periodontal and peri-implant diseases, while identifying potential miRNAs with the greatest diagnostic ability as an oral fluid biomarker. Materials and methods: Human and animal studies were included when evaluating expression of miRNAs between health and different forms/stages of diseases, in which microarray and/or real-time polymerase chain reaction (RT-PCR) was carried out to detect fold changes in gene expression. After full-text analysis, 43 articles were considered for a qualitative assessment, and 16 miRNAs were selected to perform meta-analysis. Results: Based on human studies, results showed an overall upregulation of most of the evaluated miRNAs in periodontitis, with miRNA-142-3p and miRNA-146a being the most conclusive on both microarray and RT-PCR values and potentially serving as diagnostic biomarkers for disease activity. Conversely, miR-155 was the only miRNA revealing a statistically significant difference (SSD) (p < 0.05*) in experimental periodontitis models from RT-PCR values. Scarce scientific evidence is available from peri-implant diseases, however, most explored miRNAs in peri-implantitis were downregulated except for miR-145. Conclusions: Although our results revealed that a distinct differential expression of specific miRNAs can be noted between the state of health and disease, future research remains necessary to explore the functional role of specific miRNAs and their potential as therapeutic targets in periodontal and peri-implant diseases. MeSH Terms: periodontitis, peri-implantitis, epigenomics, microarray analysis, real-time polymerase chain reaction, microRNAs. Clinical relevance: Scientific background: Although most research identified different expression levels of miRNAs in periodontal and peri-implant diseases compared to their counterparts, their actual role in the pathogenesis of these conditions remains unclear. Therefore, we aimed to present a systematic review and meta-analysis on the expression patterns of miRNAs in periodontitis and peri-implantitis, while identifying potential miRNAs with the greatest diagnostic ability as an oral fluid biomarker. Principal findings: In periodontitis-related studies, miRNA-142-3p and miRNA-146a were the most conclusive on both microarray and RT-PCR values. Scarce scientific evidence is available from peri-implant diseases. Practical implications: Both miRNA-142-3p and miRNA-146a might serve as future diagnostic biomarkers for disease activity in periodontitis. Yet, future research remains necessary to explore the functional role of specific miRNAs and their potential as therapeutic targets in periodontal and peri-implant diseases.

Peri-Implant Diseases: Diagnosis, Clinical, Histological, Microbiological Characteristics and Treatment Strategies. A Narrative Review

“…Moreover, conducting a meta-analysis on this topic has been very challenging due to the heterogeneity of the studies [ 72 ]. Regarding micro-RNA expression in peri-implantitis, there is very limited evidence on their diagnostic and prognostic value, mostly originating from animal solid peri-implant tissue studies [ 73 , 74 , 75 ]. However, in a recent human study, certain miRNA signatures appeared to be potential biomarkers for peri-implant conditions [ 76 ].…”

Research hotspots and trends of microRNA in periodontology and dental implantology: a bibliometric analysis

“…Using miRNA to induce bone formation was a hot trend in this group of studies. Most of the current studies have focused on applying miRNA with therapeutic potential to bone tissue regeneration in the form of different carriers, especially to promote osseointegration after implant implantation (24,26,57,58). However, a miRNA is often expressed in various cells and has a wide range of targets in the interconnected regulatory network, which presents high requirements for the specificity of the miRNA drug delivery system (31).…”

Epigenetic regulation of inflammation in periodontitis: cellular mechanisms and therapeutic potential

“…It should be noted that regulation of gene expression by non-coding RNAs, in particular by micro-RNAs, is classified as an epigenetic mechanism by some researchers. However, the contributions of non-coding RNAs to periodontitis pathogenesis have been reviewed elsewhere [ 25 , 26 ] and will not be covered in this review. Similarly, the involvement of epigenetic regulation in periodontal disease has been thoroughly reviewed in the context of bone metabolism [ 27 ] and potential links with oncogenesis [ 28 ], so we will not discuss these aspects extensively here.…”