An essential role of NF-kappaB 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 differentiate in vitro into various mesenchymal cell types, but inflammation prevents the multilineage differentiation. We show that the transcription factor NF-kappaB plays the key role in the repression of osteogenic and adipogenic differentiation of arthritic FLS. Furthermore, we show that specific activation of NF-kappaB profoundly enhances proliferation, motility, and matrix-degrading activity of FLS. We thus propose that arthritic FLS are mesenchymal stem cells whose differentiation is arrested at early stages of differentiation by activation of NF-kappaB.

authors

Li X,Makarov SS

doi

10.1073/pnas.0607939103

subject

Has Abstract

pub_date

2006-11-14 00:00:00

pages

17432-7

issue

46

eissn

0027-8424

issn

1091-6490

pii

0607939103

journal_volume

103

pub_type

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