MicroRNAs as Key Regulators in Periodontal Disease: A Systematic Scoping Review

Objective This systematic scoping review aimed to map and synthesize the functionally validated microRNAs (miRNAs) implicated in the pathogenesis of periodontitis using evidence from in vivo animal models and in vitro studies involving animal and human cells. The goal was to identify frequently investigated regulatory mechanisms and highlight methodological and translational research gaps. Materials and Methods A comprehensive search of PubMed, SCOPUS, and MEDLINE was conducted up to April 2025 in accordance with PRISMA-ScR guidelines. Eligible studies investigated the functional roles of miRNAs in periodontitis through experimental (in vivo or in vitro) approaches. Articles limited to bioinformatic profiling or pathway prediction were excluded. Data were charted on study design, miRNA targets, delivery methods, and outcomes, and methodological rigor was appraised using predefined quality assessment criteria. Results Ninety-six studies met the inclusion criteria: 31 in vivo animal studies, 22 in vitro animal-derived cell studies, and 43 in vitro human cell studies. Several miRNAs were recurrently examined across models, including miR-146a, miR-155, miR-21, and miR-223. miR-146a was most consistently implicated as a negative regulator of inflammation, while miR-155 and miR-21 demonstrated context-dependent roles in immune regulation and bone remodeling. Cross-study comparison was limited by heterogeneity in cell models, delivery systems, and outcome measures, and validation in human models remained insufficient. Conclusions This review highlights miRNAs as key regulators of periodontal inflammation and bone dynamics while underscoring significant methodological variability and limited human evidence. Future studies should adopt standardized protocols and integrate preclinical findings with clinical research to support translation of miRNA-based diagnostics and therapies in periodontitis.