A tumor necrosis factor-alpha antagonist inhibits inflammatory bone resorption induced by Porphyromonas gingivalis infection in mice.

Abstract

BACKGROUND:

A tumor-necrosis factor-alpha (TNF-alpha) antagonist, the WP9QY peptide, was designed based on the crystal structure of the TNF-beta/TNF-receptor complex in order to overcome the disadvantages of macromolecules such as antibodies or soluble receptors by reducing the molecular size of TNF-alpha antagonists. It efficiently antagonizes the effect of TNF-alpha 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-alpha antagonists would be beneficial for the treatment of local inflammatory bone loss induced by periodontal-pathogen infection.

• Authors: Yoshifumi Suzuki, Kazuhiro Aoki, Hiroaki Saito, Makoto Umeda, Hiroshi Nitta, Roland Baron, Keiichi Ohya
• Journal: Journal of periodontal research (J Periodontal Res) Vol. 41 Issue 2 Pg. 81-91 (Apr 2006) ISSN: 0022-3484 [Print] United States
• PMID: 16499710 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Carrier Proteins
• Membrane Glycoproteins
• Peptides, Cyclic
• RANK Ligand
• Receptor Activator of Nuclear Factor-kappa B
• Tnfrsf11a protein, mouse
• Tnfsf11 protein, mouse
• Tumor Necrosis Factor-alpha
• WP9QY peptide

Topics

• Analysis of Variance
• Animals
• Anti-Inflammatory Agents, Non-Steroidal (chemical synthesis)
• Bone Density
• Bone Resorption (etiology, prevention & control)
• Carrier Proteins (metabolism)
• Drug Design
• Infusion Pumps, Implantable
• Male
• Membrane Glycoproteins (metabolism)
• Mice
• Mice, Inbred BALB C
• Osteitis (complications, drug therapy, microbiology)
• Osteoclasts (drug effects)
• Peptides, Cyclic (administration & dosage, chemical synthesis, pharmacokinetics)
• Porphyromonas gingivalis (pathogenicity)
• Protein Binding
• RANK Ligand
• Receptor Activator of Nuclear Factor-kappa B
• Skull
• Tumor Necrosis Factor-alpha (antagonists & inhibitors)