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Updated: Aug 30, 2026
Porphyromonas gingivalis as a Model Organism for Assessing Interaction of Anaerobic Bacteria with Host Cells
Published on: December 17, 2015
Effect of hydroxamic acid-based matrix metalloproteinase inhibitors on human gingival cells and Porphyromonas
Masami Yoshioka1, Nozomi Yokoyama, Kaname Masuda
1Department of Preventive Dentistry, School of Dentistry, The University of Tokushima, Tokushima, Japan. masami@dent.tokushima-u.ac.jp
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 microM, nor was cell proliferation at 20 microM. 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.
Insights
Three hydroxamic acid-based matrix metalloproteinase (MMP) inhibitors show potential for treating periodontal disease by inhibiting MMP-2 and MMP-9 activity without harming gingival cells.
Area of Science:
- Periodontal disease research
- Drug discovery and development
- Biochemistry and molecular biology
Background:
- Matrix metalloproteinases (MMPs) are implicated in the tissue destruction characteristic of periodontitis.
- Hydroxamic acid-based MMP inhibitors (ONO-4817, ONO-MI1-514, and ONO-MI1-570) were investigated for their therapeutic potential.
Purpose of the Study:
- To evaluate the cytotoxicity of three MMP inhibitors.
- To assess their inhibitory effects on MMP-2 and MMP-9 activities.
- To determine their impact on Porphyromonas gingivalis growth and related cellular processes.
Main Methods:
- Human gingival fibroblasts (HGF) and epithelial cells (HGE) were treated with inhibitors to assess cell viability and proliferation.
- Gelatin zymography and colorimetric assays measured MMP-2 and MMP-9 inhibition.
- Effects on keratinocyte migration and P. gingivalis growth were also evaluated.
Main Results:
- Inhibitors demonstrated no cytotoxicity to gingival cells at tested concentrations.
- All three compounds dose-dependently inhibited MMP-2 and MMP-9 activity.
- ONO-4817 and ONO-MI1-514 reduced keratinocyte migration; ONO-4817 slightly inhibited P. gingivalis growth.
Conclusions:
- The tested MMP inhibitors exhibit promising therapeutic potential for periodontal disease.
- Their ability to inhibit MMPs and affect related cellular functions supports their use in treatment strategies.
- Further research is warranted to explore their clinical efficacy in preventing and treating periodontitis.
