Apoptosis and p53 expression in rat adjuvant arthritis

The kinetics of apoptosis and the apoptosis-regulating gene
p53 in adjuvant arthritis (AA) were investigated to assess the value
of the AA rat model for testing apoptosis-inducing therapies. Very few terminal
deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick
end-labeling (TUNEL)-positive cells were detected during the early phases of
AA, but on day 23 (chronic arthritis) the percentage of TUNEL-positive cells
was significantly increased. Expression of p53 in synovial tissue
gradually increased from days 5-23, which was markedly higher than p53
levels in rheumatoid arthritis (RA) synovium. Significant apoptosis only occurs
late in rat AA and is concordant with marked p53 overexpression,
making it useful model for testing proapoptotic therapies, but rat AA is not
the best model for p53 gene therapy because dramatic p53
overexpression occurs in the latter stages of the disease.