2000
DOI: 10.1002/1529-0131(200006)43:6<1226::aid-anr5>3.0.co;2-4
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Differential expression pattern of membrane‐type matrix metalloproteinases in rheumatoid arthritis

Abstract: Our results indicate a role for MT1-MMP not only in the matrix degradation by fibroblasts, but also in osteoclast-mediated bone resorption in RA. Given the ability of MT1-MMP to activate MMP-2 and MMP-13, the findings also point to a cooperation between fibroblasts and macrophages in degrading 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 destruction.

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Cited by 136 publications
(91 citation statements)
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“…The ability to inhibit MT-MMPs and the association to the extracellular matrix 22 may explain the stronger effects of TIMP-3. The abundant presence of MT-MMPs at the invasive front of the synovial tissue in RA patients compared with the synovial tissues of patients with osteoarthritis or without arthritis 7,23,10 supports the view that MT-MMPs play an important role in cartilage destruction in RA. MT-MMPs are capable of degrading cartilage macromolecules including aggrecan 24 and collagen II.…”
Section: Discussionmentioning
confidence: 54%
See 1 more Smart Citation
“…The ability to inhibit MT-MMPs and the association to the extracellular matrix 22 may explain the stronger effects of TIMP-3. The abundant presence of MT-MMPs at the invasive front of the synovial tissue in RA patients compared with the synovial tissues of patients with osteoarthritis or without arthritis 7,23,10 supports the view that MT-MMPs play an important role in cartilage destruction in RA. MT-MMPs are capable of degrading cartilage macromolecules including aggrecan 24 and collagen II.…”
Section: Discussionmentioning
confidence: 54%
“…In rheumatoid synovial tissue, increased amounts of MMPs are expressed. [5][6][7][8][9][10] Levels of MMP in the synovium and serum correlate with disease activity 11 and radiographic damage, 12,13 suggesting that MMPs play a role in the destructive process in RA. Therefore, inhibition of MMPs may be a therapeutic strategy to prevent joint destruction in RA, and the delivery of naturally occurring inhibitors of MMPs may serve as one option for achieving this goal.…”
Section: Introductionmentioning
confidence: 99%
“…MT-MMP-1 and MT-MMP-3 in particular have been detected at sites of destruction in rheumatoid arthritis (RA) (7,8). Several of these enzymes are currently considered therapeutic targets in arthritic diseases.…”
mentioning
confidence: 99%
“…On the basis of the hypothesis that furin is essential for proMT1-MMP activation, Sato and coworkers used antisense oligonucleotides against furin in human fibrosarcoma HT-1080 cells, human uterine cervical fibroblasts (HUCFs), and rabbit dermal fibroblasts (RDFs); they found that furin antisense constructs inhibited the concanavalin A-induced activation of proMMP-2 in HUCFs but not in RDFs, suggesting that there are different mechanisms of proMT1-MMP activation (16). It has also been demonstrated that MT1-MMP is expressed at elevated levels in the RA synovial membrane and particularly at sites of joint destruction (7,18,19). In addition, data obtained by Honda and coworkers (20) have shown convincingly that proinflammatory cytokines such as interleukin-1␤ up-regulate the expression of MT1-MMP in RASFs, thus potentially contributing to MT1-MMP-mediated matrix degradation in RA.…”
Section: Discussionmentioning
confidence: 99%
“…Interestingly, high expression of MT1-MMP has also been found in nonmalignant diseases that are associated with progressive matrix degradation, such as aseptic prosthesis loosening (6) and rheumatoid arthritis (RA) (7). However, the degree to which MT1-MMP contributes to the progressive destruction of articular cartilage in RA is poorly understood.…”
mentioning
confidence: 99%