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Gene expression profiling of periodontitis-affected gingival tissue by spatial transcriptomics.

ABSTRACT: Periodontitis is a highly prevalent chronic inflammatory disease of the periodontium, leading ultimately to tooth loss. In order to characterize the gene expression of periodontitis-affected gingival tissue, we have here simultaneously quantified and localized gene expression in periodontal tissue using spatial transcriptomics, combining RNA sequencing with histological analysis. Our analyses revealed distinct clusters of gene expression, which were identified to correspond to epithelium, inflamed areas of connective tissue, and non-inflamed areas of connective tissue. Moreover, 92 genes were identified as significantly up-regulated in inflamed areas of the gingival connective tissue compared to non-inflamed tissue. Among these, immunoglobulin lambda-like polypeptide 5 (IGLL5), signal sequence receptor subunit 4 (SSR4), marginal zone B and B1 cell specific protein (MZB1), and X-box binding protein 1 (XBP1) were the four most highly up-regulated genes. These genes were also verified as significantly higher expressed in gingival tissue of patients with periodontitis compared to healthy controls, using reverse transcription quantitative polymerase chain reaction. Moreover, the protein expressions of up-regulated genes were verified in gingival biopsies by immunohistochemistry. In summary, in this study, we report distinct gene expression signatures within periodontitis-affected gingival tissue, as well as specific genes that are up-regulated in inflamed areas compared to non-inflamed areas of gingival tissue. The results obtained from this study may add novel information on the genes and cell types contributing to pathogenesis of the chronic inflammatory disease periodontitis.

SUBMITTER: Lundmark A

PROVIDER: S-EPMC6008462 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Gene expression profiling of periodontitis-affected gingival tissue by spatial transcriptomics.

Lundmark Anna A Gerasimcik Natalija N Båge Tove T Jemt Anders A Mollbrink Annelie A Salmén Fredrik F Lundeberg Joakim J Yucel-Lindberg Tülay T

Scientific reports 20180619 1

Periodontitis is a highly prevalent chronic inflammatory disease of the periodontium, leading ultimately to tooth loss. In order to characterize the gene expression of periodontitis-affected gingival tissue, we have here simultaneously quantified and localized gene expression in periodontal tissue using spatial transcriptomics, combining RNA sequencing with histological analysis. Our analyses revealed distinct clusters of gene expression, which were identified to correspond to epithelium, inflam ...[more]

PMID: 29921943

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Project description:Periodontitis is a chronic disease with disturbed balance between the immune and inflammatory response of the host to bacteria. Many studies have shown that proinflammatory cytokines play a significant role in the pathogenesis of periodontal disease. In this study, we examined the association between the IL-18 gene rs187238 and rs1946518 polymorphisms and periodontitis in non-smoking and smoking patients. This study enrolled 200 patients with periodontitis (130 non-smokers and 70 smokers) and 156 control subjects (124 non-smokers and 32 smokers). There were no statistically significant differences in the distribution of the rs187238 and rs1946518 IL-18 genotypes and alleles between patients with periodontitis and control subjects, between smoking patients with periodontitis and smoking control subjects, and between non-smoking patients with periodontitis and non-smoking control subjects. There were no statistically significant differences in clinical parameters in relation to the IL18 rs187238 genotypes. In patients with the IL18 rs1946518 GG genotype, we observed increased values of bleeding on probing (BoP) and periodontal probing depth (PPD), compared to subjects with the TT genotype. In patients with periodontitis, we observed statistically significant decreased expression of the IL-18 gene in comparison with healthy subjects (0.231 ± 0.163 vs. 0.663 ± 0.197, p = 0.0008). In addition, the IL-18 gene expression in gingival tissue in patients with periodontitis correlated positively with the number of remaining teeth. The results of our study suggest that the IL-18 rs187238 and rs1946518 polymorphisms are not significant risk indicators of periodontitis in our population. However, in patients with the IL18 rs1946518 GG genotype, we observed increased values of BoP and PPD, compared to subjects with the TT genotype. In addition, in gingival tissue of patients with periodontitis, we have detected decreased expression of IL-18. The gingival expression of IL-18 in patients with periodontitis correlated positively with number of remaining teeth. The above results suggest that IL-18, in addition to its pro-inflammatory effects in periodontal disease, may also exhibit protective properties.

Project description:Although data describe the presence and increase of inflammatory mediators in the local environment in periodontitis vs. health in humans, details regarding how these responses evolve in the transition from health to disease, changes during disease progression, and features of a resolved lesion remain unknown. This study used a nonhuman primate model of ligature-induced periodontitis in young, adolescent, adult, and aged animals to document features of inflammatory response affected by age. Rhesus monkeys had ligatures tied and provided gingival tissue biopsy specimens at baseline, 0.5, 1, and 3 months of disease and at 5 months of the study, which was 2 months post-ligature removal for clinically resolved tissues. The transcriptome was assessed using microarrays for chemokine (n = 41), cytokine (n = 45), chemokine receptor (n = 21), cytokine receptor (n = 37), and lipid mediator (n = 31) genes. Limited differences were noted in healthy tissues for chemokine expression with age; however, chemokine receptor genes were decreased in young but elevated in aged samples. IL1A, IL36A, and IL36G cytokines were decreased in the younger groups, with IL36A elevated in aged animals. IL10RA/IL10RB cytokine receptors were altered with age. Striking variation in the lipid mediator genes in health was observed with nearly 60% of these genes altered with age. A specific repertoire of chemokine and chemokine receptor genes was affected by the disease process, predominated by changes during disease initiation. Cytokine/cytokine receptor genes were also elevated with disease initiation, albeit IL36B, IL36G, and IL36RN were all significantly decreased throughout disease and resolution. Significant changes were observed in similar lipid mediator genes with disease and resolution across the age groups. Examination of the microbiome links to the inflammatory genes demonstrated that specific microbes, including Fusobacterium, P. gingivalis, F. alocis, Pasteurellaceae, and Prevotella are most frequently significantly correlated. These correlations were generally positive in older animals and negative in younger specimens. Gene expression and microbiome patterns from baseline were distinctly different from disease and resolution. These results demonstrate patterns of inflammatory gene expression throughout the phases of the induction of a periodontal disease lesion. The patterns show a very different relationship to specific members of the oral microbiome in younger compared with older animals.

Dataset Information

Gene expression profiling of periodontitis-affected gingival tissue by spatial transcriptomics.

Publications

Gene expression profiling of periodontitis-affected gingival tissue by spatial transcriptomics.

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