MicroRNAs and immunity in periodontal health and disease

Abstract

MicroRNAs (miRNAs) are critical regulators of the host immune and inflammatory response against bacterial pathogens. In the present review, we discuss target genes, target gene functions, the potential regulatory role of miRNAs in periodontal tissues, and the potential role of miRNAs as biomarkers and therapeutics. In periodontal disease, miRNAs exert control over all aspects of innate and adaptive immunity, including the functions of neutrophils, macrophages, dendritic cells and T and B cells. Previous human studies have highlighted some key miRNAs that are dysregulated in periodontitis patients. In the present study, we mapped the major miRNAs that were altered in our reproducible periodontitis mouse model relative to control animals. The miRNAs that were upregulated as a result of periodontal disease in both human and mouse studies included miR-15a, miR-29b, miR-125a, miR-146a, miR-148/148a and miR-223, whereas miR-92 was downregulated. The association of individual miRNAs with unique aspects of periodontal disease and their stability in gingival crevicular fluid underscores their potential as markers for periodontal disease progression or healthy restitution. Moreover, miRNA therapeutics hold great promise for the future of periodontal therapy because of their ability to modulate the immune response to infection when applied in conjunction with synthetic antagomirs and/or relatively straightforward delivery strategies.

Fig. 1

Inflammatory connective tissue infiltrate as a result of chronic inflammatory conditions in an established/advanced periodontal lesion. Micrographs are from freshly fixed human periodontal tissues as preserved in the collection of Joseph-Peter Weinmann at the University of Illinois at Chicago. These slides were originally generated in Gottlieb’s Oral Biology Laboratory at the University of Vienna and transported to Illinois during the 1930s. a Overview micrograph illustrating the position of periodontal soft tissues in between two adjacent root surfaces (rt). The periodontal connective tissues are separated from the oral cavity by three distinct types of epithelia, junctional epithelium (je), sulcus epithelium (SE) and oral epithelium (oe). The site of the inflammatory infiltrate is identified with an asterisk (*). Note the relative loss of collagen fibres (**). b Most of the leukocyte-rich infiltrate (wbc) is located in the sub-epithelial connective tissue. c, d Higher magnification micrographs identify individual lymphocytes (lymph) as major components of the inflammatory infiltrate, suggesting that the tissue sample is from a relatively young individual.

Fig. 2

Microarray analysis of microRNA expression in periodontal progenitors from healthy individuals (Con) and animals suffering from periodontal disease (Dis). a Heat map of miRNA expression profiling. miRNAs with a significant level of upregulation or downregulation (P < 0.01) were identified using Student’s t test. Individual upregulated and downregulated genes are listed in Table 1. b Quantitative reverse transcriptase (qRT) polymerase chain reaction verification of selected microRNAs in healthy and periodontal disease tissues. There was a significant difference in miR-21, miR-29b, let-7c and miR-451 gene expression between healthy and diseased tissues.

Fig. 3

MicroRNA regulation of innate and adaptive immunity in the periodontium. Bacterial plaque on the surface of enamel and in the gingival sulcus induce immune response in the periodontium. By affecting individual target genes, microRNAs either promote or inhibit the function of innate immune cells including neutrophils, dendritic cells and macrophages, and/or the function of adaptive immune cells including T and B cells.