title: Analyses of Gingival Adhesion Molecules in Periodontitis: Theoretical In Silico, Comparative In Vivo, and Explanatory In Vitro Models.
abstract: BACKGROUND
  A deeper understanding of periodontitis pathophysiology is central to future development of novel biomarkers and therapeutics. The following is reported here: 1) an in silico network model of interactions among cell adhesion molecules and a network-focused microarray analysis of the corresponding genes in periodontitis; 2) analysis of secretions of adhesion molecules in gingival tissue samples from patients with periodontitis and healthy controls; and 3) effect of the human neutrophilic peptide-1 (HNP-1) on epithelial adhesion molecules.
  
  
  METHODS
  The network model identified 85 nodes in relation to the interactions of adhesion molecules. Subsequently, the relative gene expression was overlaid on the network model. Differential gene expression was analyzed, and false discovery rate control was performed for statistical assessment of the microarray data. Both tissue and cell culture samples were immunostained for desmocollin (DSC)2, occludin (OCLN), desmoglein (DSG)1, tight junction protein 2, and gap junction protein α.
  
  
  RESULTS
  The differential gene expression analysis revealed that the epithelial adhesion molecules were significantly lower in abundance in individuals with periodontitis than controls. In contrast, the genes for leukocyte adhesion molecules showed a significant upregulation. Immunostainings revealed elevated secretions of both DSG1 and OCLN in periodontitis. An in vitro model suggested reduced DSC2 and OCLN secretions in the presence of HNP-1.
  
  
  CONCLUSIONS
  Gene expression of gingival adhesion molecules in periodontitis is regulated by leukocyte transmigration, whereas the neutrophilic antimicrobial peptide HNP-1 is noted as a putative regulator of epithelial adhesion molecules. These observations contribute to the key mechanisms by which future biomarkers might be developed for periodontitis.
authors.affiliation: Institute of Dentistry, University of Turku, Turku, Finland.
authors.forename: Ulvi K
authors.initials: UK
authors.lastname: Gürsoy
authors.affiliation: Institute of Dentistry, University of Turku, Turku, Finland.|Department of Biochemistry, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
authors.forename: Fares
authors.initials: F
authors.lastname: Zeidán-Chuliá
authors.affiliation: Institute of Dentistry, University of Turku, Turku, Finland.|Faculty of Dentistry, Hacettepe University, Ankara, Turkey.
authors.forename: Dogukan
authors.initials: D
authors.lastname: Yilmaz
authors.affiliation: Faculty of Communications & Office of the President, International Technology and Innovation Policy, Gaziantep University, Gaziantep, Turkey.
authors.forename: Vural
authors.initials: V
authors.lastname: Özdemir
authors.affiliation: Institute of Dentistry, University of Turku, Turku, Finland.
authors.forename: Juho
authors.initials: J
authors.lastname: Mäki-Petäys
authors.affiliation: Department of Biochemistry, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
authors.forename: Ben-Hur
authors.initials: BH
authors.lastname: Neves de Oliveira
authors.affiliation: Faculty of Dentistry, Yeditepe University, Istanbul, Turkey.
authors.forename: Yigit
authors.initials: Y
authors.lastname: Firatli
authors.affiliation: Faculty of Dentistry, Hacettepe University, Ankara, Turkey.
authors.forename: Güliz N
authors.initials: GN
authors.lastname: Güncü
authors.affiliation: Faculty of Dentistry, Hacettepe University, Ankara, Turkey.
authors.forename: Feriha
authors.initials: F
authors.lastname: Caglayan
authors.affiliation: Institute of Dentistry, University of Turku, Turku, Finland.|Oral Health Care, Welfare Division, City of Turku, Turku, Finland.
authors.forename: Eija
authors.initials: E
authors.lastname: Könönen
mesh_terms: D015815:Cell Adhesion Molecules; D005881:Gingiva; D006801:Humans; D007962:Leukocytes; D062793:Occludin; D010518:Periodontitis
chemical_list: D015815:Cell Adhesion Molecules; D062793:Occludin
keywords: Biological markers; cell adhesion; defensins; gene expression; neutrophils; protein interaction maps