Bisphosfonate matrix metalloproteinase inhibitors for the treatment of periodontitis: An in vitro study
| Autor: | Cristina Campestre, Fulvio Loiodice, Paolo Tortorella, Marianna De Colli, Susi Zara, Amelia Cataldi, Mariangela Agamennone |
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| Rok vydání: | 2018 |
| Předmět: |
Lipopolysaccharides
0301 basic medicine Matrix metalloproteinase inhibitor Gingiva Matrix Metalloproteinase Inhibitors Matrix metalloproteinase Pharmacology MMP8 Zoledronic Acid Collagen Type I 03 medical and health sciences 0302 clinical medicine Genetics medicine Humans Viability assay Periodontitis Cytotoxicity Inflammation Cell Death Diphosphonates Chemistry Cell Membrane Imidazoles 030206 dentistry General Medicine Fibroblasts medicine.disease Matrix Metalloproteinases Culture Media 030104 developmental biology MMP14 Anaerobic bacteria |
| Zdroj: | International Journal of Molecular Medicine. |
| ISSN: | 1791-244X 1107-3756 |
| Popis: | Periodontitis is an inflammatory disease caused by anaerobic bacteria, including Porphyromonas gingivalis. Lipopolysaccharide (LPS)‑stimulated persistent inflammation is responsible for an increase in matrix metalloproteinase (MMP) expression, resulting in periodontal tissue destruction. The aim of the present study was to investigate synthesized bisphosphonic MMP inhibitors, in an in vitro model consisting of human gingival fibroblasts exposed to LPS, and to compare the biological responses to those induced by zoledronate (ZA), a commercial bisphosphonate. MTT and lactate dehydrogenase (LDH) assays were used to measure cell viability and cytotoxicity, respectively. ELISA was performed to evaluate prostaglandin E2 (PGE2), interleukin (IL)6 and collagen secretion, while western blotting was used to analyze MMP expression. No effect on viability and low cytotoxicity were observed following treatment with bisphosphonate compounds. In the present study, treatment with compound 1 did not increase the release of PGE2 and IL6. Increased levels of collagen I secretion were reported when compound 3 and ZA were administered. An increase of MMP8 was observed following ZA treatment, while a decrease of MMP9 and MMP14 following treatment with compounds 1, 2 and ZA were reported. The performance of compound 1 was optimal in terms of cell viability. Compound 1 also did not induce inflammation, and had the ability to counteract LPS‑induced increases in MMP expression. These data suggested that compound 1 was the most suitable treatment to progress to an in vivo animal study, with the aim to confirm its use for the treatment of periodontitis. |
| Databáze: | OpenAIRE |
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