Dysregulation of microRNA expression in chronic periodontitis

Abstract

Abstract Objective: Assess microRNA (miRNA) expression in healthy and diseased gingival tissue of human subjects and identify potential miRNA-target gene interactions and biological pathways relevant to periodontal pathogenesis. Methods: Gingival biopsies were obtained from subjects meeting the criteria for “healthy” or “diseased” according to the current AAP guidelines. Total RNA (including miRNA) was isolated using miRNeasy kit (Qiagen). Global human miRNA expression was quantified using microRNA microarray (LC Sciences μParaflo® technology platform). Potential gene targets and biological pathways of differentially expressed miRNAs were predicted using bioinformatics analysis. Results: Our results show significantly different expression levels of miRNAs when comparing inflamed and healthy gingival biopsies. Among differentially expressed miRNAs, 35 were upregulated and 29 were downregulated in diseased tissue. Using pathway analysis, these miRNAs were predicted to influence the following pathways: ECM-receptor interaction, cell adhesion molecules (CAMs), MAPK signaling pathway, and cAMP signaling pathway. Genes associated with these pathways were scanned for potential miRNA binding sites. We identified IKBKB as a target gene, an endogenous inhibitor of NF-kappa-B and MAPK signaling, which possesses multiple binding sites for candidate miRNAs including hsa-miR-195-5p. Conclusion: Our findings reveal human miRNA expression profiles are significantly different in healthy and diseased gingival tissues. Post-transcriptional regulation of gene expression by miRNAs can modulate inflammatory biological pathways, suggesting their integral role in periodontal pathogenesis.