Apoptosis and p53 expression in rat adjuvant arthritis.
STATEMENT OF FINDINGS: 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.
Tak
P P
PP
Division of Rheumatology, UCSD School of Medicine, La Jolla, California, USA. P.P.Tak@amc.uva.nl
Klapwijk
M S
MS
Broersen
S F
SF
van de Geest
D A
DA
Overbeek
M
M
Firestein
G S
GS
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D001169:Arthritis, Experimental / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D015153:Blotting, Western; D015870:Gene Expression / Q000276:immunology; D020287:In Situ Nick-End Labeling; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D013583:Synovial Membrane / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics*
D016159:Tumor Suppressor Protein p53