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Rheumatology 2001; 40: 247-255
© 2001 British Society for Rheumatology

Expression of proteinases and inflammatory cytokines in subchondral bone regions in the destructive joint of rheumatoid arthritis

M. Kaneko, T. Tomita, T. Nakase, Y. Ohsawa1, H. Seki, E. Takeuchi, H. Takano, K. Shi, K. Takahi, E. Kominami2, Y. Uchiyama1, H. Yoshikawa and T. Ochi

Department of Orthopaedic Surgery and
1 Department of Cell Biology and Anatomy I, Osaka University Medical School, Osaka and
2 Department of Biochemistry, Juntendo University School of Medicine, Tokyo, Japan

Objective. We previously described abnormalities in the bone marrow of patients with rheumatoid arthritis (RA), but were able to shed little light on the pathogenic roles of inflammatory cytokines and proteinases in joint destruction in the subchondral region in RA. This is the first report to describe the co-localization of cytokines and proteinases in this area.

Methods. Decalcified paraffin-embedded sections from 10 patients with RA and five patients with osteoarthritis (OA) were examined for the immunolocalization of cathepsins B, K and L and the localization of messenger RNAs for interleukin 1ß (IL-1ß), tumour necrosis factor {alpha} (TNF-{alpha}) and matrix metalloproteinase 9 (MMP-9). The cells were double-stained with anti-CD68 or anti-prolyl 4-hydroxylase (PH) antibody.

Results. An immunohistochemical study confirmed the expression of cathepsins B and L by CD68-positive mononuclear cells at the sites of significant cartilage and bone erosion from the subchondral region in all RA specimens. Osteoclast-like cells showed intense staining for cathepsin K and MMP-9. Osteoblast-like cells strongly expressed MMP-9. Analysis of serial sections revealed that expression of the IL-1ß and TNF-{alpha} genes occurred near that of the cathepsins and MMP-9 in the subchondral region.

Conclusion. We conclude that inflammatory cytokines and tissue-damaging proteinases play important roles in joint destruction in the subchondral region in RA.

KEY WORDS: Rheumatoid arthritis, Cathepsins, Matrix metalloproteinase 9 (MMP-9), Inflammatory cytokines, Joint destruction, Immunohistochemistry, In situ hybridization.

Correspondence to: T. Ochi, Department of Orthopaedic Surgery, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.


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