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- Title
A tumor necrosis factor-α antagonist inhibits inflammatory bone resorption induced by Porphyromonas gingivalis infection in mice.
- Authors
Suzuki, Yoshifumi; Aoki, Kazuhiro; Saito, Hiroaki; Umeda, Makoto; Nitta, Hiroshi; Baron, Roland; Ohya, Keiichi
- Abstract
Background: A tumor-necrosis factor-α (TNF-α) antagonist, the WP9QY peptide, was designed based on the crystal structure of the TNF-β/TNF-receptor complex in order to overcome the disadvantages of macromolecules such as antibodies or soluble receptors by reducing the molecular size of TNF-α antagonists. It efficiently antagonizes the effect of TNF-α binding to the TNF receptor (I) . Objectives: The aim of the present study was to assess the effects of the WP9QY peptide on inflammatory bone resorption and osteoclast formation in the periodontal pathogen-infection model. Material and methods: Live Porphyromonas gingivalis ATCC 33277 was injected once daily for 6 days into the subcutaneous tissue overlying the calvariae in mice. At the same time, the WP9QY peptide (1 mg/kg, 2 mg/kg or 4 mg/kg per day) was administrated via osmotic minipumps for 7 days. Histological observations and the radiological assessments of the calvariae as well as bone mineral density measurements were performed. Results: The WP9QY peptide significantly prevented the P. gingivalis-induced reduction in the bone mineral density at the calvariae. The histomorphometric assessments revealed the inhibitiory effects of the WP9QY peptide on the P. gingivalis-induced increase in the number of the inflammatory cells and in the area of sagittal suture at the calvariae. Furthermore, there was also an inhibitory effect on the P. gingivalis-induced increase in the number of osteoclasts per unit bone surface at the calvariae. Conclusion: These results suggest that the strategy for the design to reduce the molecular size of the TNF-α antagonists would be beneficial for the treatment of local inflammatory bone loss induced by periodontal-pathogen infection.
- Subjects
TUMOR necrosis factors; PORPHYROMONAS gingivalis; MACROMOLECULES; CALVARIA; BONES; PERIODONTAL disease
- Publication
Journal of Periodontal Research, 2006, Vol 41, Issue 2, p81
- ISSN
0022-3484
- Publication type
Article
- DOI
10.1111/j.1600-0765.2005.00812.x