title: Platelet factor 4 upregulates matrix metalloproteinase-1 production in gingival fibroblasts.
abstract: OBJECTIVE
  Periodontitis is a highly prevalent chronic inflammatory disease that causes tooth loss, morbidity and confers an increased risk for systemic disease. Tissue destruction during periodontitis is due in large part to collagen-degrading matrix metalloproteinases (MMPs) released by resident cells of the periodontium in response to proinflammatory cytokines. Platelets are immune-competent blood cells with a newly recognized role in chronic inflammation; however, their role in the pathogenesis of periodontitis is undefined. Consequently, the objective of this study was to assess the effect of platelet factor 4 (PF4), a major platelet-derived cytokine, on MMP-1 (collagenase) expression in human gingival fibroblasts (HGFs).
  
  
  METHODS
  HGFs were cultured in the presence or absence of recombinant PF4. Pro-MMP-1 secretion was quantified by enzyme-linked immunosorbent assay analysis of the cell culture supernatants. MMP-1 transcription was quantified by real-time polymerase chain reaction. Regulation of MMP-1 production by the p44/42 MAP kinase (MAPK) signaling pathway was examined in the presence or absence of PF4.
  
  
  RESULTS
  Exposure to PF4 caused a ~ 2-3-fold increase in MMP-1 transcription and secretion from cultured HGFs. PF4 treatment also enhanced phosphorylation of p44/42 MAPK, which has been previously shown to induce MMP-1 expression in fibroblasts. Blockade of p44/42 MAPK signaling with the cell-permeant inhibitors PD98059 and PD184352 abrogated PF4-induced pro-MMP-1 transcription upregulation and release from cultured HGFs.
  
  
  CONCLUSIONS
  We conclude that PF4 upregulates MMP-1 expression in HGFs in a p44/42 MAPK-dependent manner. These findings point to a previously unidentified role for platelets in the pathogenesis of periodontal diseases.
authors.affiliation: Faculty of Dentistry, University of British Columbia, Vancouver, BC, Canada.|Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Javaid
authors.affiliation: Faculty of Dentistry, University of British Columbia, Vancouver, BC, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Bi
authors.affiliation: Faculty of Dentistry, University of British Columbia, Vancouver, BC, Canada.|Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Biddle
authors.affiliation: Faculty of Dentistry, University of British Columbia, Vancouver, BC, Canada.
authors.forename: C M
authors.initials: CM
authors.lastname: Tsai
authors.affiliation: Faculty of Dentistry, University of British Columbia, Vancouver, BC, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Häkkinen
authors.affiliation: Faculty of Dentistry, University of British Columbia, Vancouver, BC, Canada.|Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada.|Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada.
authors.forename: H
authors.initials: H
authors.lastname: Kim
mesh_terms: D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000187:drug effects* / Q000201:enzymology*; D005881:Gingiva / Q000166:cytology*; D006801:Humans; D015151:Immunoblotting; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D010766:Phosphorylation; D010978:Platelet Factor 4 / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D010978:Platelet Factor 4; D020781:Matrix Metalloproteinase 1
keywords: collagenase; cytokines; fibroblast; periodontal disease; polymerase chain reaction