Premium
Effect of Hydroxamic Acid‐Based Matrix Metalloproteinase Inhibitors on Human Gingival Cells and Porphyromonas gingivalis
Author(s) -
Yoshioka Masami,
Yokoyama Nozomi,
Masuda Kaname,
Honna Tomoaki,
Hinode Daisuke,
Nakamura Ryo,
Rouabhia Mahmoud,
Mayrand Denis,
Grenier Daniel
Publication year - 2003
Publication title -
journal of periodontology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.036
H-Index - 156
eISSN - 1943-3670
pISSN - 0022-3492
DOI - 10.1902/jop.2003.74.8.1219
Subject(s) - porphyromonas gingivalis , matrix metalloproteinase , chemistry , viability assay , matrix metalloproteinase inhibitor , cell growth , periodontitis , hydroxamic acid , hacat , cytotoxicity , zymography , fibroblast , keratinocyte , cell , pharmacology , microbiology and biotechnology , biochemistry , in vitro , biology , medicine , stereochemistry
Background: Matrix metalloproteinases (MMPs) are considered to play key roles in tissue destruction during periodontitis. In this study, we evaluated the cytotoxicity of hydroxamic acid‐based MMP inhibitors (ONO‐4817, ONO‐MI1‐514, and ONO‐MI1‐570), and their inhibitory effects on MMP‐2 and ‐9 activities and growth of Porphyromonas gingivalis . Methods: Human gingival fibroblasts (HGF) and human gingival epithelial cells (HGE) were incubated with test inhibitors prior to investigating cell viability, cell proliferation, and mRNA expression for MMP‐2 and ‐9. Gelatin zymography and a colorimetric MMP assay were performed to study the inhibitory effects on MMP‐2 and ‐9 activities derived from HGF and HGE, respectively. The effect of MMP inhibitors on keratinocyte migration and P. gingivalis growth was also tested. Results: Cell viability was not affected by any of the inhibitors at a final concentration of 50 µM, nor was cell proliferation at 20 µM. All inhibitors clearly inhibited MMP‐2 produced by HGF and MMP‐9 produced by HGE in a dose‐dependent manner. No change was found in mRNA expression of MMPs by gingival cells treated with the inhibitors. ONO‐4817 and ONO‐MI1‐514 inhibited keratinocyte migration. ONO‐4817 showed a slightly inhibitory effect on the growth of P. gingivalis . Conclusion: Data obtained in this study support the potential use of the three MMP inhibitors for the prevention and treatment of periodontal disease. J Periodontol 2003;74:1219‐1224 .