Localisation of apoptosis and expression of apoptosis related proteins in the synovium of patients with rheumatoid arthritis.
OBJECTIVE
To investigate whether apoptosis occurs in the synovium of rheumatoid arthritis (RA), and the intermediate molecules operating in this process.


METHODS
DNA fragmentation was detected by in situ nick end labelling (ISNEL) in the synovium of patients with RA (n = 11) and control patients with femoral neck fracture (n = 5). The expression of proteins p53, p21WAFI/CIPI, c-myc, proliferating cell nuclear antigen (PCNA), and Bcl-2 was also examined by immunohistochemistry.


RESULTS
ISNEL positive synovial cells with apoptosis specific morphology were detected in extremely limited areas in only two RA synovial tissue specimens. Proteins p53, p21WAFI/CIPI, and c-myc, known inducers of apoptosis or cell cycle arrest or both, were expressed in the sublining cells independent of ISNEL positive cells. PCNA, a marker for cell proliferation, was observed in the synovial lining cells. Bcl-2, an inhibitor of apoptosis, was expressed mainly in infiltrated lymphocytes and in parts of the sublining layer cells of RA; it also did not correspond with ISNEL staining.


CONCLUSIONS
Our findings indicate that RA synovial cells undergo apoptosis in addition to cell proliferation, but the frequency of apoptosis was very low. We suspect that the apoptotic process in the RA synovium may be suppressed by over-expression of Bcl-2. Although expressed proteins p53, p21WAFI/CIPI, and c-myc were present in the RA synovium, these protooncogenes are probably not implicated in the apoptotic process.
Sugiyama
M
M
Department of Orthopaedic Surgery, Nagasaki University School of Medicine, Japan.
Tsukazaki
T
T
Yonekura
A
A
Matsuzaki
S
S
Yamashita
S
S
Iwasaki
K
K
D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics; D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000473:pathology*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D047428:Protein Kinase Inhibitors; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D018809:Proliferating Cell Nuclear Antigen; D047428:Protein Kinase Inhibitors; D016271:Proto-Oncogene Proteins c-myc; D016159:Tumor Suppressor Protein p53