Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 103, Issue 46, Pages 17432-17437Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0607939103
Keywords
fibroblast-like synoviocytes; mesenchymal stem cell; rheumatoid arthritis
Categories
Funding
- NIAID NIH HHS [AR/AI-44030] Funding Source: Medline
- NIAMS NIH HHS [5-P60 AR-30701-14] Funding Source: Medline
Ask authors/readers for more resources
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-kappa B plays the key role in the repression of osteogenic and adipogenic differentiation of arthritic FLS. Furthermore, we show that specific activation of NF-kappa B 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-kappa B.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available