Abstract | OBJECTIVE: METHODS: CIA was induced by primary and secondary immunizations. Osmotic minipumps were implanted in the backs of all mice on the day of the booster injection (day 21), and vehicle, anti-TNF antibody (4 mg/kg/day), or WP9QY peptide (2 mg/kg/day or 4 mg/kg/day) was continuously infused until the mice were killed (day 40). Thereafter, clinical, radiographic, and histologic assessments were performed. RESULTS: WP9QY treatment inhibited CIA-induced increases in the arthritis score, but onset of disease was not delayed by the peptide. The inhibitory effect of WP9QY on inflammation was definitely weaker than that of anti-TNF antibody. Microfocal computed tomography analyses, however, revealed that WP9QY blocked CIA-induced bone destruction at the knee joints to the same extent as did anti-TNF antibody. In addition, WP9QY inhibited synovial pannus infiltration and reduced osteoclast number. Furthermore, inhibition of CIA-induced systemic bone loss by WP9QY was more apparent than that by anti-TNF antibody. CONCLUSION: The TNFalpha antagonist WP9QY would be a useful template for the development of small molecular inhibitors to prevent both inflammatory bone destruction and systemic bone loss in rheumatoid arthritis.
|
Authors | Hiroaki Saito, Takefumi Kojima, Mariko Takahashi, William C Horne, Roland Baron, Teruo Amagasa, Keiichi Ohya, Kazuhiro Aoki |
Journal | Arthritis and rheumatism
(Arthritis Rheum)
Vol. 56
Issue 4
Pg. 1164-74
(Apr 2007)
ISSN: 0004-3591 [Print] United States |
PMID | 17393436
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Anti-Inflammatory Agents, Non-Steroidal
- Antibodies, Monoclonal
- Peptides, Cyclic
- Receptors, Tumor Necrosis Factor, Type I
- Tumor Necrosis Factor-alpha
- WP9QY peptide
|
Topics |
- Abstracting and Indexing
- Animals
- Anti-Inflammatory Agents, Non-Steroidal
(therapeutic use)
- Antibodies, Monoclonal
(pharmacology)
- Arthritis, Experimental
(drug therapy, pathology, physiopathology)
- Bone Resorption
(drug therapy, pathology)
- Dose-Response Relationship, Drug
- Hindlimb
- Joints
(drug effects, pathology, physiopathology)
- Male
- Mice
- Mice, Inbred DBA
- Osteoclasts
(drug effects, pathology)
- Peptides, Cyclic
(therapeutic use)
- Receptors, Tumor Necrosis Factor, Type I
- Severity of Illness Index
- Tomography, X-Ray Computed
(methods)
- Tumor Necrosis Factor-alpha
(antagonists & inhibitors)
|