title: Gene expression profiles in paired gingival biopsies from periodontitis-affected and healthy tissues revealed by massively parallel sequencing.
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.
authors.affiliation: Division of Periodontology, Department of Dental Medicine, Karolinska Institutet, Huddinge, Sweden. haleh.davanian@ki.se
authors.forename: Haleh
authors.initials: H
authors.lastname: Davanian
authors.forename: Henrik
authors.initials: H
authors.lastname: Stranneheim
authors.forename: Tove
authors.initials: T
authors.lastname: Båge
authors.forename: Maria
authors.initials: M
authors.lastname: Lagervall
authors.forename: Leif
authors.initials: L
authors.lastname: Jansson
authors.forename: Joakim
authors.initials: J
authors.lastname: Lundeberg
authors.forename: Tülay
authors.initials: T
authors.lastname: Yucel-Lindberg
mesh_terms: D000328:Adult; D029681:Arabidopsis Proteins / Q000235:genetics / Q000378:metabolism; D001706:Biopsy; D016022:Case-Control Studies; D019742:Chemokines, CC / Q000235:genetics* / Q000378:metabolism; D016000:Cluster Analysis; D005260:Female; D053263:Gene Regulatory Networks; D005881:Gingiva / Q000378:metabolism* / Q000473:pathology; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics* / Q000378:metabolism; D019751:Intramolecular Transferases / Q000235:genetics / Q000378:metabolism; D008297:Male; D053858:Metabolic Networks and Pathways; D008875:Middle Aged; D010518:Periodontitis / Q000378:metabolism* / Q000473:pathology; D017423:Sequence Analysis, RNA; D059467:Transcriptome; D000099218:Interferon Regulatory Factor-4
chemical_list: D029681:Arabidopsis Proteins; D019742:Chemokines, CC; D050835:Interferon Regulatory Factors; D019751:Intramolecular Transferases; D000099218:Interferon Regulatory Factor-4; C111792:CCL18 protein, human; C568454:marneral synthase, Arabidopsis