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Apoptosis and p53 expression in rat adjuvant arthritis
P P Tak1, M S Klapwijk, S F Broersen
1Division of Rheumatology, UCSD School of Medicine, La Jolla, California, USA. P.P.Tak@amc.uva.nl
Arthritis Research
|November 1, 2000
Summary
The adjuvant arthritis (AA) rat model shows significant apoptosis and p53 gene overexpression late in the disease. This makes it a useful model for testing apoptosis-inducing therapies but less ideal for p53 gene therapy.
Area of Science:
- Immunology
- Molecular Biology
- Pharmacology
Background:
- Adjuvant arthritis (AA) is a rat model used to study inflammatory arthritis.
- Apoptosis and the p53 gene play crucial roles in regulating cell death and disease progression.
Purpose of the Study:
- To evaluate the adjuvant arthritis (AA) rat model for its suitability in testing apoptosis-inducing therapies.
- To investigate the temporal dynamics of apoptosis and p53 gene expression in AA.
Main Methods:
- Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick end-labeling (TUNEL) assay to detect apoptosis.
- Quantification of p53 gene expression in synovial tissue over time.
Main Results:
- Apoptosis, detected by TUNEL-positive cells, was minimal in early AA but significantly increased by day 23 (chronic arthritis).
- p53 expression in synovial tissue gradually increased from day 5 to day 23, showing marked overexpression compared to rheumatoid arthritis (RA) synovium.
- Significant apoptosis in the AA rat model coincides with late-stage p53 overexpression.
Conclusions:
- The AA rat model is valuable for assessing proapoptotic therapies due to late-stage apoptosis and p53 overexpression.
- The model is less suitable for p53 gene therapy research because of the dramatic p53 overexpression observed in later disease stages.