Abstract
Neovascularization observed in the synovial tissue of rheumatoid arthritis is essential for the nutrition of proliferating synovial tissue; therefore, attempts have recently been made to use angiogenesis-inhibiting drugs for the treatment of arthritis. Endostatin is a C-terminal noncollagen-region fragment of type XVIII collagen, and has a potent angiogenesis-inhibiting effect. Recently, we have systemically administered endostatin to arthritic mice to investigate its arthritis-inhibiting effect. We induced the development of arthritis in 6-week-old female Balb/c mice by administrating four kinds of monoclonal anti-type II collagen antibodies followed by LPS 3 days later. Three endostatin groups of mice received 0.2 mg/kg/day, 2 mg/kg/day, or 10 mg/kg/day for 13 days before the development of arthritis, and a control group received PBS. Arthritis was evaluated by arthritis scores and hind paw thickness. In addition, the left and right foot joints were collected on the 22nd day of administration of monoclonal anti-type II collagen antibody, and histopathological preparations were made. Arthritis scores and hind paw thickness were lower in the 10 mg/kg/day group than in the control group. Histopathological examination showed that pannus formation and bone destruction were suppressed in the endostatin group compared with the control group. No severe side effects occurred in the endostatin-administered mice. These results suggest that endostatin is a promising new antiarthritic drug with few side effects and a novel mechanism of action.
