title: Age-related alterations in gene expression of gingival fibroblasts stimulated with Porphyromonas gingivalis.
abstract: OBJECTIVE
  Elderly people exhibit increased susceptibility to a number of autoimmune and infectious diseases, such as periodontitis. Although aging is reportedly associated with a decline in immune function, age-related alterations in periodontal tissue have remained elusive. In the present study, we comprehensively analyzed the effect of aging on the expression of selected genes using mouse gingival fibroblasts.
  
  
  METHODS
  Gingival fibroblasts derived from young (8 wk of age) and old (≥ 24 mo of age) C57BL/6 mice were stimulated with Porphyromonas gingivalis lipopolysaccharide or live P. gingivalis strain W83. Expression of cytokines/chemokines, innate immune receptors, growth factors, matrix metalloproteinases, tissue inhibitors of metalloproteinases and osteoclastogenesis-related molecules were evaluated using real-time polymerase chain reaction and ELISA for interleukin-6 and transforming growth factor-β1.
  
  
  RESULTS
  Gingival fibroblasts derived from old mice exhibited decreased gene expression of Il-6, Cxcl1, Tlr2, Tlr4, Irak3 (IRAK-M), Kgf, Timp1, Timp3 and Rankl under resting conditions, whereas the expression levels of Tgfβ1, Mmp3, Mmp13 and Opg were increased. Age-related differences were also detected at the protein level. Although P. gingivalis W83 upregulated Vegf, Fgf-2 and Bmp2 expression in both young and old gingival fibroblasts, the stimulatory effect on these genes was significantly lower in old gingival fibroblasts.
  
  
  CONCLUSIONS
  Our findings demonstrated that aging altered the expression of a number of genes in gingival fibroblasts. Thus, alterations in the balance of these molecules could play a critical role in periodontitis progression in the elderly.
authors.affiliation: Laboratory of Periodontology and Immunology, Division of Oral Science for Health Promotion, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan; Division of Periodontology, Department of Oral Biological Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Domon
authors.forename: K
authors.initials: K
authors.lastname: Tabeta
authors.forename: T
authors.initials: T
authors.lastname: Nakajima
authors.forename: K
authors.initials: K
authors.lastname: Yamazaki
mesh_terms: D000375:Aging / Q000235:genetics* / Q000276:immunology; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000032:analysis; D054360:Chemokine CXCL1 / Q000032:analysis; D016222:Fibroblast Growth Factor 2 / Q000032:analysis; D051523:Fibroblast Growth Factor 7 / Q000032:analysis; D005347:Fibroblasts / Q000276:immunology / Q000382:microbiology*; D005881:Gingiva / Q000276:immunology / Q000382:microbiology*; D007113:Immunity, Innate / Q000276:immunology; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis; D053592:Interleukin-1 Receptor-Associated Kinases / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000032:analysis; D019278:Matrix Metalloproteinase 3 / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000502:physiology; D053244:Osteoprotegerin / Q000032:analysis; D016966:Porphyromonas gingivalis / Q000276:immunology*; D053245:RANK Ligand / Q000032:analysis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000032:analysis; D051197:Toll-Like Receptor 4 / Q000032:analysis; D053773:Transforming Growth Factor beta1 / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
chemical_list: C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D054360:Chemokine CXCL1; C475895:Cxcl1 protein, mouse; C496454:Fgf7 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D053244:Osteoprotegerin; D053245:RANK Ligand; C560825:Timp1 protein, mouse; D019715:Tissue Inhibitor of Metalloproteinase-1; D019717:Tissue Inhibitor of Metalloproteinase-3; C493487:Tlr4 protein, mouse; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; D051197:Toll-Like Receptor 4; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D016222:Fibroblast Growth Factor 2; D051523:Fibroblast Growth Factor 7; D053592:Interleukin-1 Receptor-Associated Kinases; C507774:Irak4 protein, mouse; D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse; D019278:Matrix Metalloproteinase 3; C511769:Mmp3 protein, mouse
keywords: Porphyromonas gingivalis; aging; gingival fibroblasts; inflammation