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- Title
Platelet factor 4 upregulates matrix metalloproteinase-1 production in gingival fibroblasts.
- Authors
Javaid, M.; Bi, J.; Biddle, C.; Tsai, C. M.; Häkkinen, L.; Kim, H.
- Abstract
Background and 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). Material and 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. Conclusion 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.
- Subjects
PLATELET factor 4; METALLOPROTEINASE regulation; MATRIX metalloproteinases; PERIODONTITIS; FIBROBLASTS; POLYMERASE chain reaction; CELL culture; CELLULAR signal transduction; CHEMOKINES; ENZYMES; IN vitro studies
- Publication
Journal of Periodontal Research, 2017, Vol 52, Issue 4, p787
- ISSN
0022-3484
- Publication type
Article
- DOI
10.1111/jre.12448