Exploring the regulatory roles of MicroRNAs on NF- ΚB target genes in individuals with apical periodontitis

Objectives: This study investigated the association of miRNA-181-5p, miRNA-150-5p, miRNA-146a-5p, and miRNA-16-5p, and inflammatory genes linked to the NF-κB pathway in patients with symptomatic and asymptomatic apical periodontitis. Materials and methods: A cross-sectional study was conducted involving apical tissues from asymptomatic apical periodontitis (AAP, n = 17), symptomatic apical periodontitis (SAP, n = 15), and healthy periodontal ligament (HPL, n = 16). Expression levels of miRNA-181-5p, miRNA-150-5p, miRNA-146a-5p, and miRNA-16-5p, along with mRNA levels of IL-6, VEGF-A, HIF-1α, and NF-κB, were quantified using qPCR. Data were analyzed through descriptive statistics and regression models, including mediation analysis conducted using STATA V14 (p < 0.05). Results: mRNA levels of IL-6, VEGF-A, and NF-κB were significantly higher in SAP compared to HPL (p < 0.05), while AAP did not show differences (p > 0.05). Also, no significant differences were observed in HIF-1α expression among the groups (p > 0.05). miRNA-181-5p, miRNA-16-5p, and miRNA-146a-5p were downregulated in both AAP and SAP, compared to HPL (p < 0.05), whereas miRNA-150-5p was upregulated (p < 0.05). Negative correlations were found between miRNA-181-5p and miRNA-16-5p with IL-6, and between miRNA-181-5p and VEGF-A in AP forms (p < 0.05). Mediation analysis revealed that the upregulation of IL-6 mRNA was mediated by miRNA-16-5p in SAP. Conclusions: Apical periodontitis is associated with the downregulation of miRNA-181-5p, miRNA-16-5p, and miRNA-146a-5p and the upregulation of miRNA-150-5p. IL-6 mRNA levels seem to be regulated by miRNA-16-5p during SAP. Clinical relevance: This study provides insights into the molecular mechanisms and the inflammatory response in apical periodontitis (AP), differentiating between asymptomatic (AAP) and symptomatic forms (SAP). By identifying the specific roles of miRNAs—particularly miRNA-181-5p, miRNA-150-5p, miRNA-146a-5p, and miRNA-16-5p—on inflammation-related genes via the NF-κB pathway, the findings highlight potential diagnostic and therapeutic targets. Notably, SAP is associated with downregulation of miRNA-181-5p, miRNA-16-5p, and miRNA-146a-5p, alongside upregulation of miRNA-150-5p. The study reveals that miRNA-16-5p may modulate IL-6 gene expression during SAP, which can exacerbate inflammation and osteoclastogenesis in the affected tissues. Understanding the gene regulation of inflammatory mediators in AP can aid clinicians in personalizing management approaches, particularly in cases where traditional diagnostic methods fall short. This molecular perspective may also pave the way for miRNA-based interventions, enhancing patient outcomes by specifically targeting the inflammatory pathways underlying AP pathology.