MicroRNAs: new insights into the pathogenesis of endodontic periapical disease.

INTRODUCTION Apical periodontitis is an inflammatory disease of the periradicular tissues caused by the host's immune response to infection of the root canal system. MicroRNAs (miRNAs) have been shown to play an important role in the regulation of inflammation and the immune response; however, their role in the pathogenesis of endodontic periapical disease has not been explored. The purpose of this study was to examine the differential expression of miRNAs in diseased periapical tissues as compared with healthy controls. METHODS We first compared miRNA profiles in diseased periapical tissues collected from patients undergoing endodontic surgery with those of healthy pulps by using microarray analyses. The target genes of the differentially expressed miRNAs were identified by using miRWalk and PubMed. Selected miRNAs linked to inflammation and the immune response were then confirmed in a separate cohort of diseased and healthy tissues by using quantitative reverse transcription-polymerase chain reaction. Healthy pulps and periodontal ligaments were used as controls. Data were normalized to the level of SNORD 44, which served as an endogenous control. RESULTS Of the 381 miRNAs identified by using microarray, 24 miRNAs were down-regulated in diseased periapical tissues compared with controls (n = 13) (P < .003). The down-regulation of 7 miRNAs was confirmed from 9 selected miRNAs by using quantitative real-time polymerase chain reaction (n = 19) (P < .05). Target genes of these miRNAs include key mediators in the immune and inflammatory response such as interleukin-6, matrix metalloproteinase-9, and transforming growth factor-β. CONCLUSIONS These findings offer new insight into the pathogenesis of endodontic disease and have the potential to impact the development of new methods for prevention, diagnosis, and treatment of apical periodontitis.