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

Objective. We previously described abnormalities in the bone marrow of pati ents with rheumatoid arthritis (RA), but were able to shed little light on the pathogenic roles of inflammatory cytokines and proteinases in joint des truction in the subchondral region in RA. This is the first report to descr ibe the co-localization of cytokines and proteinases in this area. Methods. Decalcified paraffin-embedded sections from 10 patients with RA an d five patients with osteoarthritis (OA) were examined for the immunolocali zation 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) an d matrix metalloproteinase 9 (MMP-9). The cells were double-stained with an ti-CD68 or anti-prolyl 4-hydroxylase (PH) antibody. Results. An immunohistochemical study confirmed the expression of cathepsin s B and L by CD68-positive mononuclear cells at the sites of significant ca rtilage and bone erosion from the subchondral region in all RA specimens. O steoclast-like cells showed intense staining for cathepsin K and MMP-9. Ost eoblast-like cells strongly expressed MMP-9. Analysis of serial sections re vealed that expression of the IL-1 beta and TNF-alpha genes occurred near t hat of the cathepsins and MMP-9 in the subchondral region. Conclusion. We conclude that inflammatory cytokines and tissue-damaging pro teinases play important roles in joint destruction in the subchondral regio n in RA.