Possible involvement of the vascular endothelial growth factor-Flt-1-focal adhesion kinase pathway in chemotaxis and the cell proliferation of osteoclast precursor cells in arthritic joints

Yoshihiro Matsumoto, Kazuhiro Tanaka, Go Hirata, Masuo Hanada, Shuichi Matsuda, Toshihide Shuto, Yukihide Iwamoto

Research output: Contribution to journalArticlepeer-review

67 Citations (Scopus)

Abstract

Vascular endothelial growth factor (VEGF) plays a crucial role in the pathogenesis of inflammatory joint disease, including angiogenesis and synovitis. Rheumatoid arthritis is a chronic inflammatory disease characterized by progressive synovitis and subsequent bone destruction mediated by osteoclasts (OCs). In this study, we investigate the effects of VEGF on OC precursor cells (pOCs) using Raw cells and adjuvant-induced arthritis in rats. OCs and pOCs in the arthritic joints express VEGF and VEGF receptor type I (Fit-1). Raw cells also express Fit-1, and VEGF treatment stimulated chemotaxis, cell proliferation, the association of Fit-1 with focal adhesion kinase (FAK), and the tyrosine phosphorylation of FAK in Raw cells. The tyrosine phosphorylation of FAK was also observed in pOCs in the arthritic joints of adjuvant-induced arthritis. Adenovirus-mediated expression of FAK-related nonkinase in Raw cells inhibited the effects of VEGF in a dominant negative manner. Furthermore, intra-articular injection of the FAK-related nonkinase virus suppressed the recruitment of pOCs and bone destruction. Our results suggest the possible involvement of the VEGF-Flt-1-FAK pathway in inflammatory disease-induced joint destruction.

Original languageEnglish
Pages (from-to)5824-5831
Number of pages8
JournalJournal of Immunology
Volume168
Issue number11
DOIs
Publication statusPublished - Jun 1 2002

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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