Increased expression of extracellular matrix metalloproteinase inducer in rheumatoid synovium

Konttinen, Yrjö T.; Li, Tian-Fang; Mandelin, Jami; Liljeström, Mikko; Sorsa, Timo; Santavirta, Seppo; Virtanen, Ismo

doi:10.1002/1529-0131(200002)43:2<275::aid-anr6>3.0.co;2-#

Cited by 81 publications

(52 citation statements)

References 25 publications

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“…However, little EMMPRIN expression was found in synovium from OA patients. These results are consistent with the previous report by Konttinen et al (7). By RT-PCR, only 1 of the 5 synovial samples from OA patients revealed a very weak band indicating the presence of EMMPRIN mRNA.…”

Section: Discussionsupporting

confidence: 93%

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Expression of extracellular matrix metalloproteinase inducer and enhancement of the production of matrix metalloproteinases in rheumatoid arthritis

Tomita¹,

Nakase²,

Kaneko³

et al. 2002

Arthritis & Rheumatism

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Objective.To investigate the expression of extracellular matrix metalloproteinase inducer (EMMPRIN) at sites of joint destruction in rheumatoid arthritis (RA) and to correlate it with the production of matrix metalloproteinases (MMPs).Methods. Reverse transcription-polymerase chain reaction was performed to study the existence of EMMPRIN in synovial tissue derived from RA and osteoarthritis (OA) patients. In situ hybridization with a human complementary DNA specific for EMMPRIN and immunohistochemistry were performed to characterize the EMMPRIN-expressing cells at sites of joint destruction, including bone. Northern blot analysis was performed to detect the level of expression of EMMPRIN messenger RNA (mRNA) in synovial tissue. The production of MMP-1 and MMP-3 by synovial tissue from RA patients was examined by enzyme-linked immunosorbent assay.Results. Expression of EMMPRIN mRNA was detected in synovium from 9 of 11 patients with RA and 1 of 5 patients with OA. The presence of mRNA encoding EMMPRIN was recognized in the invasive synovium at sites of joint destruction in RA but not OA.

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Section: Discussionsupporting

confidence: 93%

“…EMMPRIN interacts with fibroblasts to stimulate the expressions of several MMPs associated with tissue degradation and remodeling during tumor invasion and wound healing. The expression of EMMPRIN has been shown to be up-regulated in the synovial membrane of RA patients (7). However, the contribution of EMMPRIN to joint destruction in RA is still unknown.…”

mentioning

confidence: 99%

Expression of extracellular matrix metalloproteinase inducer and enhancement of the production of matrix metalloproteinases in rheumatoid arthritis

Tomita¹,

Nakase²,

Kaneko³

et al. 2002

Arthritis & Rheumatism

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“…Additionally, through the use of CyPA mutants, the rotamase activity of CyPA was found to be important for this CD147 mediated signaling (Yurchenko et al 2002). Interestingly, the association of CyPA and CD147 is further supported by findings that increased levels of CyPA in synovial fluid and increased CD147 levels on reactive neutrophils in rheumatoid arthritis patients correlated with the severity of disease (Tegeder et al 1997;Konttinen et al 2000). Furthermore, CyPA is incorporated into HIV-1 virions and has been shown to play a role in early viral infection (Braaten et al 1996;Sherry et al 1998).…”

Section: Cyclophilinsmentioning

confidence: 96%

CD147 immunoglobulin superfamily receptor function and role in pathology

Iacono

Brown

Greene

et al. 2007

Experimental and Molecular Pathology

242

206

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The immunoglobulin superfamily member CD147 plays an important role in fetal, neuronal, lymphocyte and extracellular matrix development. Here we review the current understanding of CD147 expression and protein interactions with regard to CD147 function and its role in pathologic conditions including heart disease, Alzheimer's disease, stroke and cancer. A model linking hypoxic conditions found within the tumor microenvironment to up-regulation of CD147 expression and tumor progression is introduced.

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“…Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases, which are able to degrade almost all components of the extra-cellular matrix (Nagase and Woessner 1999). They have been considered to play a key role in the degradation of the cartilage matrix in arthritic joints (Konttinen et al 2000). The enzymatic activities of these MMPs are strictly controlled by tissue inhibitors of metalloproteinases (TIMPs).…”

Section: Rna Extraction and Quantitative Real-time Reverse Transcriptmentioning

confidence: 99%

“…TIMPs not only inhibit the activity of MMPs by binding to them in an irreversible 1 : 1 noncovalent complex (Murphy and Willenbrock 1995), but also modulate the production and activity of MMPs. Activated synovial cells in inflammation produce various types of MMPs, including collagenase-1 (MMP-1) and stromelysin-1 (MMP-3) (Okada et al 1989;Konttinen et al 2000). An imbalance of MMPs and TIMPs has been hypothesized to contribute to joint destruction in arthritis (MacNaul et al 1990;MartelPelletier et al 1994;Burger et al 1998).…”

Section: Rna Extraction and Quantitative Real-time Reverse Transcriptmentioning

confidence: 99%

Hyaluronate Inhibits the Interleukin-1.BETA.-Induced Expression of Matrix Metalloproteinase (MMP)-1 and MMP-3 in Human Synovial Cells

Sasaki

Konttinen

et al. 2004

Tohoku J. Exp. Med.

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Intra-articular administration of hyaluronate (HA) is an effective treatment for arthritis. HA injections can decrease not only joint pain but also synovial effusion, although little is known concerning the mechanism of HA action. The aim of this study was to investigate the role of HA on the expression and production of matrix metalloproteinase (MMP) in synovial cells activated by interleukin (IL)-1β in order to achieve a better understanding of exogenous HA function in the extracellular matrix degradation in arthritic joints. Human synovial cells were incubated with HA (0.1-1000 μ g/ml) and/or IL-1β (1 ng/ml). The expression of MMP-1 and MMP-3 mRNAs was analyzed by quantitative realtime polymerase chain reaction. The protein levels of MMP-1 and MMP-3 in cultured media were measured by immunoblotting. Expression of MMP-1 and MMP-3 mRNAs was induced by IL-1β . The IL-1β -mediated induction of MMP-1 mRNA expression was attenuated by 10 μ g/ml HA (p=0.026) and that of MMP-3 mRNA was strongly down-regulated in the presence of 10 or 1000 μ g/ml HA (p<0.001). The increased protein levels of MMP-1 and MMP-3 were also reduced by 1000 μ g/ml HA. These data suggest that HA inhibits the expression and production of MMP-1 and MMP-3 in IL-1β -stimulated human synovial cells. We therefore prepose that intra-articular HA may rescue inflamed joints from bone and cartilage destruction by reducing the production of MMP-1 and MMP-3.Hyaluronate; interleukin-1β ; human synovial cells; matrix metalloproteinases; tissue inhibitor of metalloproteinases

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Increased expression of extracellular matrix metalloproteinase inducer in rheumatoid synovium

Abstract: The expression of EMMPRIN is upregulated in the rheumatoid synovial membrane. EMMPRIN can induce local production of at least MMPs 1, 2, and 3, and can thereby play a role in joint destruction in RA.

Cited by 81 publications

References 25 publications

Expression of extracellular matrix metalloproteinase inducer and enhancement of the production of matrix metalloproteinases in rheumatoid arthritis

Expression of extracellular matrix metalloproteinase inducer and enhancement of the production of matrix metalloproteinases in rheumatoid arthritis

CD147 immunoglobulin superfamily receptor function and role in pathology

Hyaluronate Inhibits the Interleukin-1.BETA.-Induced Expression of Matrix Metalloproteinase (MMP)-1 and MMP-3 in Human Synovial Cells

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