Abstract
Periodontitis is a chronic inflammatory disease affecting the soft tissue and bone that surrounds the teeth. Despite extensive research, distinctive genes responsible for the disease have not been identified. The objective of this study was to elucidate transcriptome changes in periodontitis, by investigating gene expression profiles in gingival tissue obtained from periodontitis-affected and healthy gingiva from the same patient, using RNA-sequencing. Gingival biopsies were obtained from a disease-affected and a healthy site from each of 10 individuals diagnosed with periodontitis. Enrichment analysis performed among uniquely expressed genes for the periodontitis-affected and healthy tissues revealed several regulated pathways indicative of inflammation for the periodontitis-affected condition. Hierarchical clustering of the sequenced biopsies demonstrated clustering according to the degree of inflammation, as observed histologically in the biopsies, rather than clustering at the individual level. Among the top 50 upregulated genes in periodontitis-affected tissues, we investigated two genes which have not previously been demonstrated to be involved in periodontitis. These included interferon regulatory factor 4 and chemokine (C-C motif) ligand 18, which were also expressed at the protein level in gingival biopsies from patients with periodontitis. In conclusion, this study provides a first step towards a quantitative comprehensive insight into the transcriptome changes in periodontitis. We demonstrate for the first time site-specific local variation in gene expression profiles of periodontitis-affected and healthy tissues obtained from patients with periodontitis, using RNA-seq. Further, we have identified novel genes expressed in periodontitis tissues, which may constitute potential therapeutic targets for future treatment strategies of periodontitis.
Highlights
Periodontitis is a chronic inflammatory disease characterized by the destruction of periodontal tissue
With regard to disease susceptibility at a genomic level, one genome-wide association study (GWAS) has been conducted in patients with aggressive periodontitis showing an association between aggressive periodontitis and intronic single nucleotide polymorphism rs1537415, which is located in the glycosyltransferase gene GLT6D1 [11]
This study provides a novel quantitative comprehensive mapping of gene expression in gingival tissues from patients diagnosed with periodontitis, using RNA-Seq
Summary
Periodontitis is a chronic inflammatory disease characterized by the destruction of periodontal tissue. One microarray study reported no significant differences in gene expression at different pathological sites in patients with chronic and aggressive periodontitis [4], whereas Kim et al [5] and Demmer et al [6] showed a number of genes that were upregulated in periodontitis compared to healthy controls. With regard to in vitro studies, gene expression profiling has been performed on gingival fibroblasts from inflamed and healthy gingival tissues, for a limited number of inflammatory markers, such as interleukin (IL)-1, IL-6, IL-8, tumor necrosis factor- a (TNF-a) and CD14 [8]. With regard to disease susceptibility at a genomic level, one genome-wide association study (GWAS) has been conducted in patients with aggressive periodontitis showing an association between aggressive periodontitis and intronic single nucleotide polymorphism rs1537415, which is located in the glycosyltransferase gene GLT6D1 [11]
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