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

Mould, Arne W., Tonks, Ian D., Cahill, Marian M., Pettit, Allison R., Thomas, Ranjeny, Hayward, Nicholas K. and Kay, Graham F. (2003) Vegfb gene knockout mice display reduced pathology and synovial angiogenesis in both antigen-induced and collagen-induced models of arthritis. Arthritis and Rheumatism, 48 9: 2660-2669. doi:10.1002/art.11232


Author Mould, Arne W.
Tonks, Ian D.
Cahill, Marian M.
Pettit, Allison R.
Thomas, Ranjeny
Hayward, Nicholas K.
Kay, Graham F.
Title Vegfb gene knockout mice display reduced pathology and synovial angiogenesis in both antigen-induced and collagen-induced models of arthritis
Journal name Arthritis and Rheumatism   Check publisher's open access policy
ISSN 0004-3591
Publication date 2003-01-01
Sub-type Article (original research)
DOI 10.1002/art.11232
Volume 48
Issue 9
Start page 2660
End page 2669
Total pages 10
Editor D. S. Pisetsky
Place of publication New York, USA
Publisher John Wiley & Sons
Collection year 2003
Language eng
Subject C1
321020 Pathology
730114 Skeletal system and disorders (incl. arthritis)
110316 Pathology (excl. Oral Pathology)
Formatted abstract
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.
Keyword Rheumatology
Endothelial Growth-factor
High-affinity Binding
Factor-b
Rheumatoid-arthritis
Tyrosine Kinase
Vascular-permeability
Deficient Mice
Orf Virus
Receptor
Expression
Q-Index Code C1

 
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Created: Wed, 15 Aug 2007, 05:31:53 EST