2006
DOI: 10.1073/pnas.0607939103
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An essential role of NF-κB in the “tumor-like” phenotype of arthritic synoviocytes

Abstract: A hallmark of rheumatoid arthritis is the formation of an aggressive, tumor-like structure called pannus that erodes the joint. A major cellular component of the pannus is the fibroblast-like synoviocyte (FLS), whose morphology strikingly resembles that of a transformed cell, but underlying mechanisms of this ''transformation'' are not known. Here, using animal models of rheumatoid arthritis, we show that arthritic FLS contain a substantial (>30%) fraction of bone marrow-derived precursors that can differentia… Show more

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Cited by 110 publications
(111 citation statements)
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References 38 publications
(41 reference statements)
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“…The low activation of NFkB detected in GICs suggests that NFkB may be dispensable for survival and proliferation of these tumor NFjB blockade promotes senescence of differentiating GICs L Nogueira et al progenitor cells, which correlates with data showing that p65 immunoreactivity is abundant in the cytoplasm of the majority of cells within neurospheres derived from embryonic mouse brain, but only occasional weak nuclear localization (active state) is detected (Young et al, 2006). NFkB has been described to function as an inducer and an inhibitor of differentiation, which reflects its heterogeneity in activities depending on the cell system studied (Zhang et al, 1998;Li and Makarov, 2006;Pevsner-Fischer et al, 2007;Vaira et al, 2008). We showed that blockade of NFkB by using genetic strategies or small-molecule inhibitors accelerate maturation of differentiating GICs.…”
Section: Discussionsupporting
confidence: 68%
“…The low activation of NFkB detected in GICs suggests that NFkB may be dispensable for survival and proliferation of these tumor NFjB blockade promotes senescence of differentiating GICs L Nogueira et al progenitor cells, which correlates with data showing that p65 immunoreactivity is abundant in the cytoplasm of the majority of cells within neurospheres derived from embryonic mouse brain, but only occasional weak nuclear localization (active state) is detected (Young et al, 2006). NFkB has been described to function as an inducer and an inhibitor of differentiation, which reflects its heterogeneity in activities depending on the cell system studied (Zhang et al, 1998;Li and Makarov, 2006;Pevsner-Fischer et al, 2007;Vaira et al, 2008). We showed that blockade of NFkB by using genetic strategies or small-molecule inhibitors accelerate maturation of differentiating GICs.…”
Section: Discussionsupporting
confidence: 68%
“…In the tissue site, FLS may receive growth-promoting signals from neighboring fibroblasts as well as through the secreted form of the ligand. FLS have long been recognized as displaying almost autonomous features in terms of their proliferative response, a characteristic that has encouraged discussions on whether these cells are tumorlike (35,36). The autocrine growth loop described here, fueled by FKN, may well contribute to the hyperplastic reaction pattern of mesenchymal cells in sites of inflamed tissue.…”
Section: Discussionmentioning
confidence: 99%
“…Although not genuine MSCs, circulating CD14 + monocytes may contain progenitors with the potential to differentiate into mesenchymal cells (Kuwana et al, 2003). In terms of the underlying mechanism for the transformation-like phenotype of FLSs, and the involvement of MSCs, Li & Makarov (2006) reported intriguing data from animal models of RA. Arthritic FLSs contained a substantial fraction of bone marrow-derived precursors, with the ability to differentiate in vitro into various mesenchymal cell types.…”
Section: Mouse Models For Ramentioning
confidence: 91%
“…On the other hand, specific activation of NF-B profoundly enhanced proliferation, motility, and matrix-degrading activity of FLSs by the induction of MMPs. These data suggest an intriguing mechanism, namely, that arthritic FLSs are bone marrow-derived MSCs, which are arrested during the early stages of differentiation, by the activation of NF-B induced by inflammatory cytokines (Li & Makarov, 2006).…”
Section: Mouse Models For Ramentioning
confidence: 99%