RNA-sequencing study of peripheral blood monocytes in chronic periodontitis

• The functions of monocytes in periodontitis were first explored with RNA-seq.
• There was pervasive up-regulation of transcripts at isoform level in periodontitis.
• Novel signatures: FACR & CUX1 genes, endocytosis, cytokine production & apoptosis

BackgroundMonocytes are an important cell type in chronic periodontitis (CP) by interacting with oral bacteria and mediating host immune response. The aim of this study was to reveal new functional genes and pathways for CP at monocyte transcriptomic level.MethodsWe performed an RNA-sequencing (RNA-seq) study of peripheral blood monocytes (PBMs) in 5 non-smoking moderate to severe CP (case) individuals vs. 5 controls. We took advantage of a microarray study of periodontitis to support our findings. We also performed pathway-based analysis on the identified differentially expressed (DEx) transcripts/isoforms using DAVID (Database for Annotation, Visualization and Integrated Discovery).ResultsThrough differential expression analyses at both whole gene (or whole non-coding RNA) and isoform levels, we identified 380 DEx transcripts and 5955 DEx isoforms with a PPEE (posterior probability of equal expression) of < 0.05. Pervasive up-regulation of transcripts at isoform level in CP vs. control individuals was observed, suggesting a more functionally active monocyte transcriptome for CP. By comparing with the microarray dataset, we identified several CP-associated novel genes (e.g., FACR and CUX1) that have functions to interact with invading microorganisms or enhance TNF production on lipopolysaccharide stimulation. DAVID analysis of both the RNA-seq and the microarray datasets leads to converging evidence supporting “endocytosis”, “cytokine production” and “apoptosis” as significant biological processes in CP.ConclusionsAs the first RNA-seq study of PBMs for CP, this study provided novel findings at both gene (e.g., FCAR and CUX1) and biological process level. The findings will contribute to better understanding of CP disease mechanisms.