Immunolocalisation studies on six matrix metalloproteinases and their inhibitors, TIMP-1 and TIMP-2, in synovia from patients with osteo- and rheumatoid arthritis.

Hembry, Rosalind M.; Bagga, M. R.; Reynolds, John J.; Hamblen, David L.

doi:10.1136/ard.54.1.25

Cited by 152 publications

(126 citation statements)

References 34 publications

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“…Matrix metalloproteinases (MMPs) are thought to play an important role in the matrix degradation of OA (4)(5)(6). Although the mechanism of the rapid destruction of the hip joint in this subgroup of OA is still unknown, previous biochemical studies suggest that fibroblasts from the synovium and subchondral cysts may secrete much higher levels of MMPs than are typically secreted in ordinary OA (7,8).…”

Section: Discussionmentioning

confidence: 99%

Significant increases in serum and plasma concentrations of matrix metalloproteinases 3 and 9 in patients with rapidly destructive osteoarthritis of the hip

Masuhara

Nakai

Yamaguchi

et al. 2002

Arthritis & Rheumatism

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Objective. Rapidly destructive osteoarthritis (OA) of the hip is an uncommon subset of OA that affects mainly elderly women. Previous studies indicate that elevated levels of matrix metalloproteinases (MMPs) are produced within the tissue of patients with the condition. In the present study, we sought to determine whether serum and plasma levels of MMPs and tissue inhibitors of metalloproteinases (TIMPs) are also elevated.Methods. Blood samples were obtained from 16 patients with rapidly destructive hip OA and from 20 patients with OA before total hip arthroplasty was performed. Synovial specimens were obtained during surgery. Synovial fibroblasts that had migrated sufficiently from explants were subcultured in vitro for 72 hours after confluency, and harvested supernatants were collected. Blood, tissue samples, and fibroblasts were assayed for MMPs 1, 2, 3, and 9, and TIMPs 1 and 2 by sandwich enzyme immunoassay.Results. In blood samples, the levels of MMP-3 and MMP-9 in the group with rapidly destructive hip OA were significantly higher than the normal range and were also significantly higher than those in the OA group. In tissue samples, the levels of MMP-1, MMP-3, MMP-9, and TIMP-1 in the group with rapidly destructive hip OA were significantly higher than those in the OA group. Conclusion.The results of this study show that serum and plasma levels of MMP-3 and MMP-9 are significantly increased in patients with rapidly destructive hip OA. Significantly large amounts of these MMPs produced in synovial tissues within the hip joint could contribute in part to elevation of blood levels. Detection of increased levels of MMP-3 and MMP-9 in patients with painful, disabling hip OA may be of diagnostic value for rapidly destructive hip OA.

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Section: Discussionmentioning

confidence: 99%

Significant increases in serum and plasma concentrations of matrix metalloproteinases 3 and 9 in patients with rapidly destructive osteoarthritis of the hip

Masuhara

Nakai

Yamaguchi

et al. 2002

Arthritis & Rheumatism

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“…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%

Cartilage degradation and invasion by rheumatoid synovial fibroblasts is inhibited by gene transfer of TIMP-1 and TIMP-3

Laan

Quax

Seemayer³

et al. 2003

Gene Ther

103

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Matrix metalloproteinases (MMPs) are believed to be pivotal enzymes in the invasion of articular cartilage by synovial tissue in rheumatoid arthritis (RA). Here, we investigated the effects of gene transfer of tissue inhibitors of metalloproteinases (TIMPs) on the invasiveness of RA synovial fibroblasts (RASF) in vitro and in vivo. Adenoviral vectors (Ad) were used for gene transfer. The effects of AdTIMP-1 and AdTIMP-3 gene transfer on matrix invasion were investigated in vitro in a transwell system. Cartilage invasion in vivo was studied in the SCID mouse coimplantation model for 60 days. In addition, the effects of AdTIMP-1 and AdTIMP-3 on cell proliferation were investigated. A significant reduction in invasiveness was demonstrated in vitro as well as in vivo in both the AdTIMP-1-and AdTIMP-3-transduced RASF compared with untransduced SF or SF that were transduced with control vectors. In vitro, the number of invading cells was reduced to 25% (Po0.001) in the AdTIMP-1-transduced cells and to 13% (Po0.0001) in the AdTIMP-3-transduced cells (% of untransduced cells). Cell proliferation was significantly inhibited by AdTIMP-3 and, less, by AdTIMP-1. In conclusion, overexpression of TIMP-1 and TIMP-3 by Ad gene transfer results in a marked reduction of the invasiveness of RASF in vitro and in the SCID mouse model. Apart from the inhibition of MMPs, a reduction in proliferation rate may contribute to this effect. These results suggest that overexpression of TIMPs, particularly TIMP-3 at the invasive front of pannus tissue, may provide a novel therapeutic strategy for inhibiting joint destruction in RA.

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“…However, in terms of mole ratios, the degree of increase in expression of MMPs and ADAMs that break down the ECM may differ from that of the TIMPs that suppress MMP and ADAM activities. As with rheumatoid synovial fluid [9,22], levels of MMPs and ADAMs are believed to be greater than levels of TIMPs, and the balance between decomposition and suppression systems may be disrupted in chondrosarcoma. Cells weakly immunoreactive for ADAMs and TIMPs are detected in normal cartilage, as these compounds probably function in normal cartilage metabolism.…”

Section: Discussionmentioning

confidence: 99%

Expression of Matrix Metalloproteinase, a Disintegrin and Metalloproteinase, and Tissue Inhibitor of Metalloproteinase in Human Chondrosarcoma

Sugita

Osaka

Toriyama

et al. 2004

Acta Histochem. Cytochem

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Malignant degree of human chondrosarcoma can be difficult to determine using only histological findings. We therefore assessed expression of matrix metalloproteinases (MMPs), a disintegrin and metalloproteinase (ADAM) with thrombospondin motifs (ADAMTSs) and tissue inhibitor of metalloproteinases (TIMPs) in chondrosarcoma and ascertained relationships to histological degree of malignancy. As methods, in 28 chondrosarcoma cases, immunostaining was performed using antibodies against MMP 2, 3, 7, 9, 13, ADAMTS 4, 5 and TIMP 1, 2, 3. Chondrosarcoma were classified into groups of 7, 15 and 6 cases based on histologically malignant grade I, II and III, respectively. All target proteins were expressed in chondrosarcoma. Positive correlations (p<0.05) existed between immunostaining scores and histological grades for all proteins except MMP 9, with strong correlations (p<0.01) for MMPs 2, 3 and 13, both ADAMTSs and all 3 TIMPs. It was concluded that these proteins could be used to indicate degree of malignancy in human chondrosarcoma.

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Immunolocalisation studies on six matrix metalloproteinases and their inhibitors, TIMP-1 and TIMP-2, in synovia from patients with osteo- and rheumatoid arthritis.

Cited by 152 publications

References 34 publications

Significant increases in serum and plasma concentrations of matrix metalloproteinases 3 and 9 in patients with rapidly destructive osteoarthritis of the hip

Significant increases in serum and plasma concentrations of matrix metalloproteinases 3 and 9 in patients with rapidly destructive osteoarthritis of the hip

Cartilage degradation and invasion by rheumatoid synovial fibroblasts is inhibited by gene transfer of TIMP-1 and TIMP-3

Expression of Matrix Metalloproteinase, a Disintegrin and Metalloproteinase, and Tissue Inhibitor of Metalloproteinase in Human Chondrosarcoma

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