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The effect of endostatin evaluated in an experimental animal model of collagen-induced arthritis
Authors:Kurosaka D  Yoshida K  Yasuda J  Yasuda C  Noda K  Furuya K  Ukichi T  Kingetsu I  Joh K  Yamaguchi N  Saito S  Yamada A
Affiliation:Division of Rheumatology, Department of Internal Medicine, Jikei University School of Medicine, 3-25-8, Nishi-shinbashi, Minato-ku, Tokyo 105-8461, Japan. d_kurosaka@jikei.ac.jp
Abstract:OBJECTIVE: To investigate the arthritis-inhibiting effect of endostatin, a potent angiogenesis inhibitor, on type II collagen-induced arthritis (CIA). METHODS: In an experimental system of prophylactic administration, endostatin was administered once daily at 1 mg/kg/day or 10 mg/kg/day for 2 weeks from before the onset of arthritis. In the experimental system of therapeutic administration, mice with an arthritis score of 1 to 3 were administered endostatin once daily at 10 mg/kg. In the experimental system of continuous administration, endostatin was administered using an osmotic pump capable of continuously administering a calculated dose of 1 mg/kg/day for 2 weeks. RESULTS: Arthritis scores were lower in a dose-dependent manner in the prophylactic administration group than in the control group. Arthritis scores were lower in the therapeutic administration group than in the control group. Compared with the once-daily dosage regimen, the administration of endostatin by an osmotic pump achieved a similar arthritis-inhibiting effect at one-tenth of the dose. CONCLUSION: Both prophylactic and therapeutic administration of endostatin inhibited type II CIA in mice. The administration method using an osmotic pump is useful.
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