Rheumatoid arthritis and p53: how oxidative stress might alter the course of inflammatory diseases
✍ Scribed by Paul P. Tak; Nathan J. Zvaifler; Douglas R. Green; Gary S. Firestein
- Book ID
- 104299186
- Publisher
- Elsevier Science
- Year
- 2000
- Tongue
- English
- Weight
- 582 KB
- Volume
- 21
- Category
- Article
- ISSN
- 0167-5699
No coin nor oath required. For personal study only.
✦ Synopsis
ibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA) exhibit many features of transformed cells 1 -they can proliferate in an anchorage-independent manner 2 , lack contact inhibition and express several oncogenes characteristic of cells that have escaped normal growth-regulatory mechanisms 3 . Genetic analysis of synovial cells in RA is indicative of oligoclonal expansion at the site of cartilage invasion 4 . Furthermore, populations of long-term-cultured RA FLS (but not normal FLS or osteoarthritis FLS) invade the cartilage matrix after co-implantation with cartilage explants into severe combined immunodeficiency (SCID) mice 5 . These observations led us to investigate whether a 'transformation' of cells at the site of inflammation could be caused by the development of permanent genetic changes.
There is increasing evidence that reactive oxygen species (ROS) and reactive nitrogen species (RNS), which are produced endogenously at sites of chronic inflammation, have genotoxic effects 6 . The subsequent DNA damage activates the tumor suppressor gene p53 (also known as TP53), thereby inducing cell growth arrest, which allows time for DNA repair 7 . When DNA damage is extensive, cells may undergo apoptosis, thereby ensuring that such cells either die or repair their DNA. However, p53 mutations can also occur,