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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 (Flt-1). Raw cells also express Flt-1, and VEGF treatment stimulated chemotaxis, cell proliferation, the association of Flt-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.

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Objective. To evaluate the relationship between the frequency of peripheral CD57؉ T cells and the physical status of rheumatoid arthritis (RA) patients, and to perform cytokine analysis of these CD57؉ T cells.Methods. Four-color fluorescence-activated cell sorter analysis was performed to detect both cell surface antigens and intracellular cytokines in peripheral blood leukocytes, using monoclonal antibodies against CD3, CD4, CD8, CD57, interferon-␥ (IFN␥), and interleukin-4 (IL-4). RA patients were clinically evaluated with a modified Health Assessment Questionnaire (M-HAQ), joint score, face scale, and visual analog scale (VAS) assessing pain and disease activity.Results. There was a significant correlation between the frequency of CD4؉,CD57؉ T cells and erythrocyte sedimentation rate (ESR), whereas a correlation was not found between the frequency of CD8؉,CD57؉ T cells and ESR. The frequency of CD4؉,CD57؉ T cells also showed a significant correlation with the mHAQ score, VAS, and face scale. Again, there was no significant correlation between the above-mentioned clinical scores and the frequency of CD8؉,CD57؉ T cells. Flow cytometric analysis of intracellular cytokines revealed that 14.5% of the CD57؉ T cells produced IFN␥, whereas only 2.8% of the CD57؉ T cells produced IL-4 in RA patients.Conclusion. Evidence showing that the frequency of CD4؉,CD57؉ T cells among CD3؉ cells of RA patients had a significant correlation not only with ESR but also with the physical status of the patients, and that a large proportion of the CD4؉,CD57؉ T cells had the capacity to produce IFN␥, strongly suggests that these CD4؉,CD57؉ T cells are involved in the immunopathogenesis of RA.

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