Gene expression profile analysis of rheumatoid synovial fibroblast cultures revealing the overexpression of genes responsible for tumor-like growth of rheumatoid synovium

Induction of Notch signaling by tumor necrosis factor in rheumatoid synovial fibroblasts

“…Although the target genes are yet to be elucidated, it is possible that the TNF-mediated NF-kB activation induces Jagged-2 and elicits the Notch signaling in the adjacent synovial cells of the developing joints, thus promoting differentiation of primordial synovial cells. We have recently reported the evidence suggesting that the genetic phenotype of synovial fibroblasts is ontogenically reversed, at least in part, during the rheumatoid inflammatory process and discussed that this revertant phenotype of RSF may be responsible for the selfperpetuating character of RA (Watanabe et al, 2002). These findings suggest the involvement of Notch signaling in RA pathophysiology as well as in the joint Figure 4 Immunohistochemical detection of Notch-1, Notch-4, and Jagged-2 in synovial tissues from patients with RA and OA.…”

“…Interestingly, somatic mutations of the p53 tumor suppressor gene have been demonstrated in RA tissues and RSF (Yamanishi et al, 2002). In addition, we have recently found the upregulation of the stromal cell-derived factor 1 and platelet-derived growth factor receptor a, which are considered responsible for the formation of primordial joint tissue during the embryonic development, are overexpressed in RSF, even in the absence of inflammatory cytokines and growth factors (Watanabe et al, 2002).…”

DNA methylation regulates the expression of CXCL12 in rheumatoid arthritis synovial fibroblasts

“…[17][18][19][20] Previous studies also showed that cultured RASFs produce more CXCL12 than NSFs or OASFs. 16,21 Based on these results, we analyzed in the current work whether expression of CXCL12 in RASFs is modified by changes in DNA methylation. Furthermore, to elucidate CXCL12 signaling pathways we looked at the expression of CXCR7 in SFs and tested whether CXCR7 mediates the production of matrix metalloproteinases (MMPs) after CXCL12 stimulation in RASFs.…”

Gene Expression Profiling in Rheumatoid Arthritis

“…Reversibly, the soluble factors, such as cytokines and growth factors released from the immune cells, in combination with cell-cell interactions likely activate FLS and influence their behavior. One of the first gene expression analyses of in-vitro cultured FLS clearly demonstrated over-expression of genes responsible for tumor-like growth (Watanabe et al, 2002). Analysis of the expression of 588 known cancer-related genes revealed increased expression of PDGFR , PAI-1 and SDF1A by FLS from five patients with RA compared to FLS from five traumatic control patients.…”