Subcutaneous injections of a TNF-alpha antagonistic peptide inhibit both inflammation and bone resorption in collagen-induced murine arthritis.
The cyclic peptide WP9QY (YCWSQYLCY), which was designed to mimic the most critical tumor necrosis factor (TNF) alpha recognition loop on type1 TNF receptor, antagonizes the effects of TNFalpha. In this study, we investigated the effects of WP9QY peptide on collagen-induced arthritis (CIA) mice to evaluate its effects on inflammatory bone destruction. DBA/1J mice were injected intradermally at the base of the tail with bovine type II collagen, emulsified in complete Freund's adjuvant on day 0 and 21. The three sets of WP9QY peptide injections (24 mg/kg x 8 times per day) were performed before the onset of paw swelling. Mice were sacrificed at day 38 and thereafter, the arthritis scores as well as radiographical and histological outcomes were assessed. WP9QY peptide inhibited CIA-induced increase in the arthritis score. Furthermore, histomorphometric analysis of the tibial epiphysis region revealed that WP9QY peptide inhibited the increase of synovial pannus infiltration and the decrease of bone volume, which were induced by the CIA. The WP9QY treatment prevented the inflammation as well as bone destruction of the joints in the CIA mice, suggesting that the administration of WP9QY peptide might be useful for developing a drug to prevent inflammatory bone destruction.
Kojima
Takefumi
T
Maxillofacial Surgery, Department of Maxillofacial Reconstruction and Function, Graduate School, Tokyo Medical and Dental University, Japan.
Aoki
Kazuhiro
K
Nonaka
Kiichi
K
Saito
Hiroaki
H
Azuma
Miyuki
M
Iwai
Hideyuki
H
Varghese
Bobby J
BJ
Yoshimasu
Hidemi
H
Baron
Roland
R
Ohya
Keiichi
K
Amagasa
Teruo
T
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000188:drug therapy*; D001862:Bone Resorption / Q000517:prevention & control*; D002417:Cattle; D024043:Collagen Type II; D007249:Inflammation / Q000517:prevention & control; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D010456:Peptides, Cyclic / Q000627:therapeutic use*; D011485:Protein Binding / Q000187:drug effects; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D024043:Collagen Type II; D010456:Peptides, Cyclic; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; C501648:WP9QY peptide