Bisphosfonate matrix metalloproteinase inhibitors for the treatment of periodontitis: An in vitro study

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...

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Bibliographic Details
Published in:International journal of molecular medicine 2018-07, Vol.42 (1), p.651-657
Main Authors: De Colli, Marianna, Tortorella, Paolo, Agamennone, Mariangela, Campestre, Cristina, Loiodice, Fulvio, Cataldi, Amelia, Zara, Susi
Format: Article
Language:English
Subjects:
Acids
Bacteria
Care and treatment
Collagen
Cytokines
Cytotoxicity
Development and progression
Diphosphonates
Disease
Extracellular matrix
Fibroblasts
Genetic aspects
Gum disease
Health aspects
Patient outcomes
Periodontitis
Protease inhibitors
Tumor necrosis factor-TNF
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Summary: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 ([PGE.sub.2]) 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 [PGE.sub.2] 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. Key words: bisphosphonate, human gingival fibroblast, lipopolysaccharide, metalloproteinases, periodontitis, zoledronate
ISSN:1107-3756
1791-244X
DOI:10.3892/ijmm.2018.3641