PT  - JOURNAL ARTICLE
AU  - C A Seemayer
AU  - S Kuchen
AU  - M Neidhart
AU  - P Kuenzler
AU  - V Řihošková
AU  - E Neumann
AU  - M Pruschy
AU  - W K Aicher
AU  - U Müller-Ladner
AU  - R E Gay
AU  - B A Michel
AU  - G S Firestein
AU  - S Gay
TI  - p53 in rheumatoid arthritis synovial fibroblasts at sites of invasion
AID  - 10.1136/ard.2003.007401
DP  - 2003 Dec 01
TA  - Annals of the Rheumatic Diseases
PG  - 1139--1144
VI  - 62
IP  - 12
4099  - http://ard.bmj.com/content/62/12/1139.short
4100  - http://ard.bmj.com/content/62/12/1139.full
SO  - Ann Rheum Dis2003 Dec 01; 62
AB  - Objective: To analyse the functional response of p53 in rheumatoid arthritis synovial fibroblasts (RASF) in vitro and in vivo and to investigate whether activation of p53 modulates the destructive process of RASF. Methods: RASF and controls grown on chamber slides were either directly examined with DO7 anti-p53 antibodies by immunofluorescence or irradiated with 10 Gy x rays and analysed time dependently for the expression of p53. The percentage of positive cells was evaluated by a quantitative scoring system. RASF and normal (N) SF cultured in vitro were co-implanted with human cartilage in SCID mice for 60 days. Consecutively, the invasion score was evaluated, and the number of p53 positive cells was determined at the sites of invasion by immunohistochemistry. In addition, synovial tissues from RA, osteoarthritis, and normal synovia were stained with DO7 antibodies. Results: In vitro the rate of expression of p53 in RASF was low (<5%), but transiently inducible by ionising irradiation (50%). In vitro low p53 expressing RASF disclosed, when invading articular cartilage, a nuclear p53 signal in 20% of the cells, indicating the induction of p53 in a distinct population of RASF during the invasive process. Conclusions: These data suggest an inductive p53 response at sites of cartilage invasion during the destructive process driven by activated RASF.