Fibroblast growth factor-2 determines severity of joint disease in adjuvant-induced arthritis in rats

A. Yamashita, Y. Yonemitsu, S. Okano, K. Nakagawa, Y. Nakashima, T. Irisa, Y. Iwamoto, Y. Nagai, M. Hasegawa, K. Sueishi

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107 Citations (Scopus)


Rheumatoid arthritis (RA), a systemic inflammatory disease of unknown etiology, mainly affects synovial joints. Although angiogenic growth factors, including fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF), may play a critical role in the development and progression of RA joint disease, little information is now available regarding their exact role in initiation and/or progression of RA. In this study, we show that both polypeptides were up-regulated in the rat joint synovial tissue of an adjuvant-induced model of arthritis (AIA), as well as human subjects with RA. FGF-2 overexpression via Sendai virus-mediated gene transfer significantly worsened clinical symptoms and signs of rat AIA, including hind paw swelling and radiological bone destruction, as well as histological findings based on inflammatory reaction, synovial angiogenesis, pannus formation, and osteocartilaginous destruction, associated with up-regulation of endogenous VEGF. FGF-2 gene transfer to non-AIA joints was without effect. These findings suggested that FGF-2 modulated disease progression, but did not affect initiation. Reverse experiments using anti-FGF-2-neutralizin rabbit IgG attenuated clinical symptoms and histopathological abnormalities of AIA joints. To our knowledge, this is the first report indicating direct in vivo evidence of disease-modulatory effects of FGF-2 in AIA, as probably associated with endogenous VEGF function. FGF-2 may prove to be a possible therapeutic target to treat subjects with RA.

Original languageEnglish
Pages (from-to)450-457
Number of pages8
JournalJournal of Immunology
Issue number1
Publication statusPublished - Jan 1 2002

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology


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