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.

中文翻译：

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在实验性牙周炎中，粒细胞集落刺激因子（G-CSF）调节中性粒细胞浸润和牙周组织破坏。

尽管粒细胞集落刺激因子（G-CSF）在几种免疫炎性疾病中具有致病作用，但尚未研究其在牙周炎中的作用。在这里，我们使用基因表达综合（GEO）数据库中的公共数据集检测了G-CSF的局部表达，并基于单样本基因集富集分析（ssGSEA）估计了免疫细胞浸入牙龈组织中。G-CSF表达和中性粒细胞浸润也通过人牙龈活检分析得到了证实。此外，局部施用抗G-CSF中和抗体以研究G-CSF中和对牙周炎小鼠模型中嗜中性粒细胞浸润和牙周组织破坏的影响。两个公开数据集（GSE10334和GSE16134）包括424名牙周炎患者和133名健康对照，被用于分析。与对照组相比，牙周炎组的牙龈组织中的免疫细胞浸润和G-CSF表达明显增加。G-CSF的高表达与免疫细胞的浸润有关，特别是与中性粒细胞浸润有关。牙龈活检的分析进一步证实中性粒细胞浸润和G-CSF表达高。另外，与用同种型对照抗体治疗的牙周炎小鼠相比，用抗G-CSF抗体治疗的牙周炎小鼠表现出明显减少的牙槽骨吸收和中性粒细胞浸润。同样，抗G-CSF抗体治疗可显着降低CXC趋化因子（CXCL1，CXCL2和CXCL3），白介素1β（IL-1β），IL-6，基质金属蛋白酶9的mRNA表达，牙周组织中核因子κB配体/骨保护素（RANKL / OPG）比率和破骨细胞数量的受体激活剂。总之，发炎的牙龈组织中的中性粒细胞浸润和G-CSF表达水平显着增加。G-CSF中和牙周炎可以减轻实验性牙周炎中性粒细胞的浸润和牙周组织的破坏。