Journal
RHEUMATOLOGY
Volume 40, Issue 3, Pages 247-255Publisher
OXFORD UNIV PRESS
DOI: 10.1093/rheumatology/40.3.247
Keywords
rheumatoid arthritis; cathepsins; matrix metalloproteinase 9 (MMP-9); inflammatory cytokines; joint destruction; immunohistochemistry; in situ hybridization
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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 1 beta (IL-1 beta), 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-1 beta 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.
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