The role of matrix metalloproteinases (MMPs) in the arthritides

Journal/Book: Z Rheumatol 1998; 57: 180. 1998;

Abstract: Dr. Vera Knäuper; School of Biological Sciences University of East Anglia Norwich In rheumatoid arthritis (RA) proliferation of synovial cells infiltration of lymphoid cells and chronic inflammation leads to the destruction of joint tissue. Although the causative mechanisms and the sequence of events leading to the chronic manifestation of the disease are still hypothetical it is known that matrix metalloproteinases (MMPs) play a critical role in the development of RA. They are involved in the early stages of RA pathogenesis when synovial fibroblasts show a transformed phenotype and a variety of other cell types begin to proliferate and show a degradative phenotype which is established by the overexpression of MMPs as a response to a local cytokine imbalance. Our current interest has focussed on studying the expression of a number MMPs in chondrocyte derived cellular model systems and the analysis of cellular mechanisms leading to proenzyme activation in order to further understand the proteolytic mechanisms leading to enhanced extracellular connective tissue turnover. We have used a chondrosarcoma cell line to study the expression of procollagenase-3 progelatinase A progelatinase B and stromelysin-1 in response to IL-1( oncostatin M and concanavalin A. Our results show that procollagenase-3 and progelatinase B expression is enhanced by IL-1( and oncostatin M treatment of the cells. Upon treatment with concanavalin A activation of procollagenase-3 progelatinase A and progelatinase B were demonstrated which was due to the expression of a membrane associated member of the matrix metalloproteinase family MT1-MME Inhibitor studies revealed that this proteolytic cascade was solely dependent on MMP activity and could be regulated by the tissue inhibitors of metalloproteinases TIMP-2 and TIMP-3. ... le

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