Genes related to inflammation and bone loss process in periodontitis suggested by bioinformatics methods.
BACKGROUND
Despite of numerous studies on periodontitis, the mechanism underlying the progression of periodontitis still remains largely unknown. This study aimed to have an expression profiling comparison between periodontitis and normal control and to identify more candidate genes involved in periodontitis and to gain more insights into the molecular mechanisms of periodontitis progression.


METHODS
The gene expression profile of GSE16134, comprising 241 gingival tissue specimens and 69 healthy samples as control which were obtained from 120 systemically healthy patients with periodontitis (65 with chronic and 55 with aggressive periodontitis), was downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) in periodontitis samples were screened using the limma package in R compared with control samples. Gene Ontology (GO) and pathway enrichment analysis upon the DEGs were carried out using Hypergeometric Distribution test. Protein-protein interaction (PPI) network of the DEGs was constructed using Cytoscape, followed by module selection from the PPI network using MCODE plugin. Moreover, transcription factors (TFs) of these DEGs were identified based on TRANSFAC database and then a regulatory network was constructed.


RESULTS
Totally, 762 DEGs (507 up- and 255 down-regulated) in periodontitis samples were identified. DEGs were enriched in different GO terms and pathways, such as immune system process, cell activation biological processes, cytokine-cytokine receptor interaction, and metabolic pathways. Cathepsin S (CTSS) and pleckstrin (PLEK) were the hub proteins in the PPI network and 3 significant modules were selected. Moreover, 19 TFs were identified including interferon regulatory factor 8 (IRF8), and FBJ murine osteosarcoma viral oncogene homolog B (FOSB).


CONCLUSIONS
This study identified genes (CTSS, PLEK, IRF-8, PTGS2, and FOSB) that may be involved in the development and progression of periodontitis.
Department of Stomatology, The Fifth People's Hospital of Shanghai, Fudan University, No.128, Ruili Rd, Minhang District, Shanghai, 200240, China. slenll@163.com.
Liang
L
Song
Department of Endodontics, Shanghai Oral Disease Prevention and Cure Center, Shanghai, 200031, China. yjueqi@126.com.
Jueqi
J
Yao
Department of Stomatology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan Province, China. hwzhjing@126.com.
Zhijing
Z
He
Department of Stomatology, The Fifth People's Hospital of Shanghai, Fudan University, No.128, Ruili Rd, Minhang District, Shanghai, 200240, China. xubbinn@163.com.
Bin
B
Xu
D010520:Aggressive Periodontitis / Q000235:genetics; D016301:Alveolar Bone Loss / Q000235:genetics*; D001798:Blood Proteins / Q000235:genetics; D002403:Cathepsins / Q000235:genetics; D055113:Chronic Periodontitis / Q000235:genetics; D019295:Computational Biology; D051546:Cyclooxygenase 2 / Q000235:genetics; D018450:Disease Progression; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics; D010518:Periodontitis / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics; D054730:Protein Interaction Domains and Motifs / Q000235:genetics; D060066:Protein Interaction Maps / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D000099185:Interferon Regulatory Factor-8
D001798:Blood Proteins; D002403:Cathepsins; D051546:Cyclooxygenase 2; D050835:Interferon Regulatory Factors; D010750:Phosphoproteins; D016760:Proto-Oncogene Proteins c-fos; D014157:Transcription Factors; D000099185:Interferon Regulatory Factor-8; C064269:FOSB protein, human; C039077:platelet protein P47; C496540:PTGS2 protein, human; C028217:cathepsin S