Chemically modified tetracyclines stimulate matrix metalloproteinase-s production by periodontal ligament cells
article
Background and Objective: The purpose of this study was to investigate the effects of chemically modified tetracyclines (CMTs) on the production of gelatinases [matrix metalloproteinase (MMP)-2 and -9] by human periodontal ligament (PDL) cells, and on the activity of recombinant gelatinases. Material and Methods: Human PDL cells were cultured with CMT-1, -3, -5, -7 or -8 in concentrations of 0, 1, 5, 10, 20, 50, 100, 200 and 500 μm. Gelatin zymography was used to determine MMP-2 and -9 production of the cells. The amount of DNA present in the cultures was analyzed using a fluorescent assay. The cytotoxicity of the CMTs was also determined. Recombinant human MMP-2 and -9 were incubated with the CMTs (0-500 μm) and their activity was analyzed using an internally quenched fluorogenic substrate. Results: MMP-2 production was stimulated up to sevenfold by CMT-1, -3, -7 and -8 at low concentrations (10-200 μm). No significant amounts of MMP-9 were produced. In contrast, MMP-2 and -9 activity was reduced by ≈ 10-40-fold at higher concentrations (200-500 μm). CMT-5 had no effect on the production or on the activity of MMP-2 and -9. Only CMT-3 and -8 had cytotoxic effects on the PDL cells at the highest concentrations. Conclusion: Surprisingly, CMTs are able to stimulate MMP-2 production at relatively low concentrations. However, at higher concentrations they exert a much stronger inhibitory effect on gelatinase activity. A possible stimulatory effect of CMTs on MMP production should be considered in their clinical use. © 2006 The Authors. Chemicals / CAS: DNA, 9007-49-2; gelatin, 9000-70-8; gelatinase A, 146480-35-5; gelatinase B, 146480-36-6; DNA, 9007-49-2; Enzyme Inhibitors; Gelatin, 9000-70-8; Matrix Metalloproteinase 2, EC 3.4.24.24; Matrix Metalloproteinase 9, EC 3.4.24.35; Recombinant Proteins; Tetracyclines
Topics
Biomedical ResearchChemically modified tetracyclinesGelatin zymographyMatrix metalloproteinasesPeriodontal ligamentDNAEnzyme inhibitorGelatinGelatinase AGelatinase BRecombinant proteinTetracycline derivativeAnalysis of varianceIosynthesisCell cultureChemistryDrug antagonismDrug effectHumanMetabolismNonparametric testPeriodontal ligamentPolyacrylamide gel electrophoresisWestern blottingAnalysis of VarianceBlotting, WesternCells, CulturedDNAElectrophoresis, Polyacrylamide GelEnzyme InhibitorsGelatinHumansMatrix Metalloproteinase 2Matrix Metalloproteinase 9Periodontal LigamentRecombinant ProteinsStatistics, NonparametricTetracyclines
TNO Identifier
89084
ISSN
00223484
Source
Journal of Periodontal Research, 41(5), pp. 463-470.
Pages
463-470
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