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

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 ( MMP s) 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 ( PF 4), a major platelet‐derived cytokine, on MMP ‐1 (collagenase) expression in human gingival fibroblasts ( HGF s). Material and Methods HGF s were cultured in the presence or absence of recombinant PF 4. 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 PF 4. Results Exposure to PF 4 caused a ~ 2–3‐fold increase in MMP ‐1 transcription and secretion from cultured HGF s. PF 4 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 PD 98059 and PD 184352 abrogated PF 4‐induced pro‐ MMP ‐1 transcription upregulation and release from cultured HGF s. 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.