Therapeutic effects of sunitinib, one of the anti-angiogenetic drugs, in a murine arthritis

Abstract

Objectives. The purpose of this study was to confirm the inhibitory effects of sunitinib, an angiogenesis inhibitor that targets tyrosine kinases of vascular endothelial growth factor receptor (VEGFR) family and platelet-derived growth factor receptor (PDGFR) family, on arthritis in mice with type II collagen-induced arthritis (CIA).

Methods. Sunitinib at a concentration of 30 or 60 mg/kg/day was intraperitoneally administered to mice with CIA. We compared the changes in arthritis score over time, pathological score, bone density, and microvascular density in synovial membrane between the vehicle and treatment groups.

Results. In the sunitinib-treated groups, the arthritis score decreased in a dose-dependent manner in comparison with that in the vehicle group. Furthermore, improvement in the pathological score, inhibitory tendency of loss in the bone density, and a decrease in the synovial microvascular density were also observed in the sunitinib-treated groups.

Conclusions. Sunitinib remarkably inhibited arthritis, particularly synovial angiogenesis in a murine CIA model. This compound may be useful for treating arthritis.

Keywords:

• Angiogenesis
• Collagen-induced arthritis
• Platelet-derived growth factor
• Sunitinib
• Synovitis
• Vascular endothelial growth factor

Acknowldegements

I am deeply grateful to Dr. Saito, M.D., Ph.D., Associate Professor and Head of the Department of Molecular Immunology at Jikei University, who provided carefully considered feedback and valuable comments. I would also like to thank Dr. Akiyama, Ph.D., Assistant Professor of the Department of Molecular Immunology at Jikei University, whose meticulous comments were an enormous help to me. Finally, I gratefully appreciate the financial support of JSPS KAKENHI, a Grant-in-Aid for Scientific Research (C) (No. 23591448), that made it possible to complete my thesis.

Conflict of interest

None.