Vegfb gene knockout mice display reduced pathology and synovial angiogenesis in both antigen-induced and collagen-induced models of arthritis

被引:111
作者
Mould, AW
Tonks, ID
Cahill, MM
Pettit, AR
Thomas, R
Hayward, NK
Kay, GF
机构
[1] Queensland Inst Med Res, Transgen Lab, Brisbane, Qld 4006, Australia
[2] Harvard Univ, Inst Med, Beth Israel Deaconess Med Ctr, New England Baptist Bone & Joint Inst, Boston, MA USA
[3] Univ Queensland, Princess Alexandra Hosp, Ctr Immunol & Canc Res, Brisbane, Qld, Australia
来源
ARTHRITIS AND RHEUMATISM | 2003年 / 48卷 / 09期
关键词
D O I
10.1002/art.11232
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective. To determine the role of vascular endothelial growth factor B (VEGF-B) in 2 mouse models of arthritis, antigen-induced arthritis (AIA) and collagen-induced arthritis (CIA). Methods. For AIA studies, monarticular AIA was induced by methylated bovine serum albumin (mBSA) priming of Vegfb gene knockout (Vegfb(-/-)) and wild-type (Vegfb(+/+)) mice, followed by intraarticular injection of mBSA or saline control 8 days later. CIA was induced in Vegfb(-/-) and Vegfb(+/+) mice by intradermal injection of chick type II collagen in adjuvant. Arthritis was monitored in both models using defined criteria (clinical and histologic). Angiogenesis was measured by synovial vessel density in diseased and control joints. Results. In AIA studies, Vegfb(+/+) mice displayed significant knee joint swelling and synovial inflammation 7 days after intraarticular injection of antigen. Synovial inflammation was associated with angiogenesis, since vessel density in AIA synovium was significantly higher in arthritic than in control joints from the same animal. Knee joint swelling, synovial inflammation, and inflammation-associated vessel density in arthritic joints were reduced in Vegfb(-/-) mice compared with arthritic joints from Vegfb(+/+) mice. Similarly, in CIA, both disease incidence and mean clinical severity scores were significantly reduced in Vegfb(-/-) mice compared with Vegfb(+/+) mice. Mean histologic severity scores and mean synovial vessel density were reduced in diseased joints from Vegfb(-/-) mice when compared with diseased joints from Vegfb(+/+) mice. Conclusion. The reduction in inflammation-associated synovial angiogenesis in Vegfb(-/-) mice implicates VEGF-B in pathologic vascular remodeling in inflammatory arthritis. VEGF-B may be an attractive target in the design of anti-angiogenic therapies for rheumatoid arthritis.
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页码:2660 / 2669
页数:10
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