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Ann Rheum Dis. Dec 2003; 62(12): 1139–1144.
PMCID: PMC1754413

p53 in rheumatoid arthritis synovial fibroblasts at sites of invasion


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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
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Figures and Tables

Figure 1
Immunofluorescence for p53 in irradiated and non-irradiated RASF: (A) RASF 6 in passage 3 irradiated with 10 Gy x rays; (B) RASF 6 in passage 3 non-irradiated; (C) RASF 7 in passage 11 irradiated with 10 Gy x rays; (D) RASF 7 in passage 11 non-irradiated. ...
Figure 2
Irradiation of RASF, NSF, and FSFB with 10 Gy x rays and fixation after distinct times. Expression of p53 was determined by immunofluorescence. p53 was transiently induced by ionising irradiation after 2.5 hours in all investigated fibroblast types. ...
Figure 3
Immunohistochemistry of p53 using DO7 antibodies in SCID mice sections of NSF, RASF, and SV40 transformed cells. In NSF, only limited invasion, but hardly any p53 signal was detectable. In RASF, expression of p53 was found in some cartilage invading ...
Figure 4
Quantification of p53 positive cells at sites of invasion in the SCID mouse co-implantation model of RA. Data are expressed as means (SD). On average, p53 was expressed during the invasive process in 20% of cartilage invading RASF. In vitro, the same ...
Figure 5
Immunohistochemistry of p53 with DO7 antibodies of RA tissue specimens and controls. Limited expression of p53 was detected in RA synovium, but no expression in normal synovium. Strong nuclear p53 expression was found in a neurological tumour (positive ...

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