Differential expression pattern of membrane-type matrix metalloproteinasesin rheumatoid arthritis

Objective. To study the expression of messenger RNA (mRNA) for different me mbrane-type matric metalloproteinases (MT-MMPs) and compare their expressio n pattern in rheumatoid arthritis (RU) and normal synovium. Methods. Polymerase chain reaction (PCR) with specific primers was performe d to analyze the presence of MT1-, MT2-, MT3-, and MT4-MMP in synonial tiss ue and synovial fibroblasts from 10 patients with RA and 1 subjects without arthritis. In addition, in situ hybridization with digosigenin-labeled RNA probes was used to investigate the expression pattern of MT-MMPs in the sy novium of these subjects. MT-MMP-expressing cells were characterized by imm unohistochemical double labeling with anti-CD68 monoclonal antibodies. Results, Reverse transcription-PCR revealed the expression of MT1-, MT2-, M T3-, and MT4-MMP mRNA in all tissues and cell cultures examined. However, i n situ hybridization showed considerable differences in the expression patt ern of the different MT-MMPs in Ri synovium. MT1- and MT3-,1-MMP mRNA were highly expressed in both the lining and the sublining layer, with more inte nse staining in the lining. Immunohistochemical double labeling demonstrate d the presence of mRNA for MT1-MMP in fibroblasts and macrophages, as well as in osteoclast-like cells at sites of bone resorption. Expression of MT3- MMP mRNA. was seen in fibroblasts and some macrophages. Expression of MT2- and MT4-MMP was characterized by staining of only a few CD68-negative fibro blasts, and no differences could be found between the lining and sublining, Normal Synovial samples showed only limited staining for all MT-MMPs. Conclusion. Our results indicate a role for MT1-MMP not only in the matrix degradation by fibroblasts, but also in osteoclast-mediated bone resorption in Ri, Given the ability of MT1-MMP to activate MMP-2 and MMP-13, the find ings also point to a cooperation between fibroblasts and macrophages in deg rading cartilage and bone. While MT3-MMP is also intensely expressed in RA synovium? MT2- and MT4-MMP appear not to be involved in rheumatoid joint de struction.