Granulocyte colony stimulating factor (G-CSF) regulates neutrophils infiltration and periodontal tissue destruction in an experimental periodontitis

Abstract

Although granulocyte colony-stimulating factor(G-CSF) has pathogenic roles in several immune inflammatory diseases, its role in periodontitis has not been investigated. Here we detected local expression of G-CSF using public datasets in the Gene Expression Omnibus (GEO) database, and immune cell infiltration into gingival tissue was estimated based on single-sample gene set enrichment analysis (ssGSEA). G-CSF expression and neutrophil infiltration were also confirmed by human gingival biopsies analysis. Moreover, anti-G-CSF neutralizing antibody was locally administrated to investigate the effects of G-CSF neutralization on neutrophils infiltration and periodontal tissue destruction in periodontitis mice model. Two public datasets (GSE10334 and GSE16134), which included 424 patients with periodontitis and 133 health controls, were used in the analysis. Markedly increased immune cell infiltration and G-CSF expression in gingival tissues were found in the periodontitis group as compared to the control group. The higher expression of G-CSF was correlated with higher infiltration of immune cells, especially with neutrophil infiltration. Analysis of gingival biopsies further confirmed high neutrophil infiltration and G-CSF expression. In addition, anti-G-CSF antibody-treated mice with periodontitis showed significantly reduced alveolar bone resorption and neutrophil infiltration when compared with periodontitis mice treated with isotype control antibody. Also, anti-G-CSF antibody treatment significantly reduced mRNA expression of CXC chemokines (CXCL1, CXCL2 and CXCL3), interleukin 1β (IL-1β), IL-6, matrix metalloproteinases 9, receptor activator of nuclear factor κB ligand/osteoprotegerin (RANKL/OPG) ratio and osteoclasts number in periodontal tissues. In summary, neutrophil infiltration and G-CSF expression levels were significantly increased in inflamed gingival tissues. G-CSF neutralization in periodontal inflammation could alleviate neutrophil infiltration and periodontal tissue destruction in experimental periodontitis.