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Platelet factor 4 upregulates matrix metalloproteinase-1 production in gingival fibroblasts

University of British Columbia

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 pro-inflammatory 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 (ELISA) analysis of the cell culture supernatants. MMP-1 transcription was quantified by real-time polymerase chain reaction (qPCR). 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 human gingival fibroblasts (HGFs). PF4 treatment also enhanced phosphorylation of p44/42 MAP kinase (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 platelet factor 4 upregulates MMP-1 expression in human gingival fibroblasts in a p44/42 MAPK-dependent manner. These findings point to a previously unidentified role for platelets in the pathogenesis of periodontal diseases.

Text

2017-01-21

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/60244

Craniofacial Science

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/