Gene Expression Signatures Of Foreign Body Reaction In Normal Peri-Implant Soft-Tissue

Abstract

Objectives: To analyse similarities in gene expression patterns of peri-implant soft tissue and foreign body reaction affected macrophages. Methods: Publicly available microarray data of gene-expression (Affymetrix Rat Genome 230-2.0 Array) from normal rat peri-implant soft-tissue (GSE43744) and experimentally induced early foreign body reaction (FBR) affected rat macrophages (GSE21682) were obtained from NCBI- Gene Expression Omnibus (GEO). Differentially expressed genes (DEG) in peri-implant soft-tissue versus oral mucosa (PI-DEG) and FBR affected versus normal blood macrophages (FBR-DEG) were each determined using the GEO2R tool (adjusted p-value<0.01). Genes shared between PI-DEG and FBR-DEG were analyzed (PI-FBR-DEG). Functional annotation based clustering for the shared PI-FBR-DEG was done based on Gene Ontology (GO) profiles and KEGG database. Protein-Protein interaction (PPI) networks were also made. Results: 283 PI-DEG had significant differential expression in peri-implant soft tissue as compared to oral mucosa, while 1426 FBR-DEG were significantly different in foreign body affected macrophages as compared to normal controls. Among these, 30 PI-FBR-DEG were identified as shared where 15 PI-FBR-DEG had log2 fold change >2 in peri-implant tissue, the top DEG being; interleukin 1 beta, SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1, cysteine rich protein 1, carbonic anhydrase 2, and Fc fragment of IgG receptor. 4 GO and 4 KEGG based enriched functional clusters were noted. Enriched GO terms were; ‘response to LPS’, ‘positive regulation of apoptosis’, ‘response to Vitamin D’ while KEGG pathways were; ‘NF-kappa B signaling pathway’, ‘TNF signaling pathway’, and ‘Leishmaniasis.’ HCK and CSF2RB (IL-3 receptor common beta subunit) were dominant hub genes in the PPI network. Conclusions: Bioinformatic analysis revealed gene expression and signalling pathway signatures common to clinically normal peri-implant soft-tissue and foreign body reaction affected macrophages.