Increased expression of integrins on fibroblast-like synoviocytes from rheumatoid arthritis in vitro correlates with enhanced binding to extracellular matrix proteins

Rinaldi, Nadia; Schwarz-Eywill, M; Weis, D; Leppelmann-Jansen, P; Lukoschek, M.; Keilholz, Ulrich; Barth, Thomas F.E.

doi:10.1136/ard.56.1.45

Cited by 87 publications

(94 citation statements)

References 26 publications

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“…The data obtained in this study have shown that ICAM-1 and VCAM-1 expression was greater in RA synovium than in OA ST. These results suggest that first, despite significantly higher expression of adhesion molecules (ICAM-1 and VCAM-1) in RA compared with OA ST, their ligands in inflammatory cells (␣ L /␤ 2 and ␣ 4 ␤ 1 , respectively) may not be overexpressed because they are regulated by other cytokines, such as TGF-␤1; may be absent or inactivated [36,38]. Probably because of this we could not observe differences in size and type of inflammatory infiltrates in RA ST compared with OA ST. Second, synovial membrane from RA was probably differentially stimulated by overexpressed proinflammatory cytokines than OA synovial tissue, although cytokine gene expression was similar between OA and RA groups.…”

Section: Discussionmentioning

confidence: 90%

Interleukin‐8, Interleukin‐10, Intercellular Adhesion Molecule‐1 and Vascular Cell Adhesion Molecule‐1 Expression Levels are Higher in Synovial Tissue from Patients with Rheumatoid Arthritis than in Osteoarthritis

Furuzawa‐Carballeda

Alcocer‐Varela

1999

Scand J Immunol

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The aim of this work was to determine differences in pro‐ and anti‐inflammatory cytokine and adhesion molecule expression in synovial tissue from patients with rheumatoid arthritis (RA) or osteoarthritis (OA). Synovial tissue samples were obtained from patients with RA and OA, and from healthy individuals. The expression of mRNA of interleukin (IL)‐1β, IL‐4, IL‐6, IL‐8, IL‐10, IL‐13, tumour necrosis factor‐α (TNF‐α) and transforming growth‐factor‐β1 (TGF‐β1) was evaluated by the polymerase chain reaction (PCR). In addition, IL‐8 and IL‐10 transcripts were measured by quantitative PCR. The expression of IL‐8 and IL‐10 proteins was determined by immunoperoxidase staining. To evaluate the inflammatory stage of synovial tissue, vascular cell adhesion molecule‐1 (VCAM‐1) and intercellular adhesion molecule‐1 (ICAM‐1) protein expression was also determined. RA patients were found to display higher levels of adhesion molecules than patients with OA. PCR analysis showed a similar profile of cytokine transcripts between the OA and RA groups. Gene expression of IL‐4 and IL‐13 in synovium was undetectable. In contrast, IL‐1β, IL‐6, IL‐8, IL‐10, TNF‐α and TGF‐β1 transcripts were expressed by both groups. Increased levels of IL‐8 and IL‐10 transcripts and their proteins were observed in synovium from RA patients when compared to patients with OA and healthy controls. Thus, our data show that IL‐8, IL‐10, ICAM‐1 and VCAM‐1 expression levels are higher in synovial tissue from patients with RA than in similar tissue from patients with OA.

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Section: Discussionmentioning

confidence: 90%

Interleukin‐8, Interleukin‐10, Intercellular Adhesion Molecule‐1 and Vascular Cell Adhesion Molecule‐1 Expression Levels are Higher in Synovial Tissue from Patients with Rheumatoid Arthritis than in Osteoarthritis

Furuzawa‐Carballeda

Alcocer‐Varela

1999

Scand J Immunol

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“…RGD-binding integrins are highly expressed in the normal synovium. 9,10,12,13,19 We further evaluated the potential of the RGD-modified adenoviruses for transduction of the synovium by measuring the mRNA level for ␣ v in synovial cells. The ␣ v subunit was used as this subunit is most frequently present in RGD binding integrins.…”

Section: Discussionmentioning

confidence: 99%

“…19 The significance of the modulation for the RGD adenoviral trans- duction efficiency is not clear. Especially as Reynolds et al 24 have shown that the transgene expression profile can not be correlated with the expression for a particular integrin.…”

Section: Discussionmentioning

confidence: 99%

A tropism-modified adenoviral vector increased the effectiveness of gene therapy for arthritis

et al. 2001

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“…37,38 a5b1 integrins are also expressed in RA-SF, showing a significant increase compared with normal SF. 39 Thus, SF from OA patients would synthetize aggrecanases after 45-kDa Fn-fs stimulation through integrins engagement. Our data suggest that in stages of SF hyperplasia in OA, Fn-fs could establish a feedback loop contributing to the maintenance of cartilage erosion.…”

Section: Q17mentioning

confidence: 99%

Healthy and Osteoarthritic Synovial Fibroblasts Produce a Disintegrin and Metalloproteinase with Thrombospondin Motifs 4, 5, 7, and 12

Pérez‐García

Gutiérrez‐Cañas

Seoane

et al. 2016

The American Journal of Pathology

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Current description of osteoarthritis includes the involvement of synovial inflammation. Studies contributing to understanding the mechanisms of cross-talk and feedback among the joint tissues could be relevant to the development of therapies that block disease progression. During osteoarthritis, synovial fibroblasts exposed to anomalous mechanical forces and an inflammatory microenvironment release factors such as a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) metalloproteinases that mediate tissue damage and perpetuate inflammation. We therefore studied the production of ADAMTS by synovial fibroblasts and their contribution to cartilage degradation. Moreover, we analyzed the implication of two mediators present in the osteoarthritis joint, IL-1b as proinflammatory cytokine, and 45-kDa fibronectin fragments as products of matrix degradation. We reported that synovial fibroblasts constitutively express and release ADAMTS 4, 5, 7, and 12. Despite the contribution of both mediators to the stimulation of Runx2 and Wnt/b-catenin signaling pathways, as well as to ADAMTS expression, promoting the degradation of aggrecan and cartilage oligomeric matrix protein from cartilage, fibronectin fragments rather than IL-1b played the major pathological role in osteoarthritis, contributing to the maintenance of the disease. Moreover, higher levels of ADAMTS 4 and 7 and a specific regulation of ADAMTS-12 were observed in osteoarthritis, suggesting them as new potential therapeutic targets. Therefore, synovial fibroblasts provide the biochemical tools to the chronicity and destruction of the osteoarthritic joints. (Am J Pathol 2016, -: 1e13; http:// dx

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Increased expression of integrins on fibroblast-like synoviocytes from rheumatoid arthritis in vitro correlates with enhanced binding to extracellular matrix proteins

Cited by 87 publications

References 26 publications

Interleukin‐8, Interleukin‐10, Intercellular Adhesion Molecule‐1 and Vascular Cell Adhesion Molecule‐1 Expression Levels are Higher in Synovial Tissue from Patients with Rheumatoid Arthritis than in Osteoarthritis

Interleukin‐8, Interleukin‐10, Intercellular Adhesion Molecule‐1 and Vascular Cell Adhesion Molecule‐1 Expression Levels are Higher in Synovial Tissue from Patients with Rheumatoid Arthritis than in Osteoarthritis

A tropism-modified adenoviral vector increased the effectiveness of gene therapy for arthritis

Healthy and Osteoarthritic Synovial Fibroblasts Produce a Disintegrin and Metalloproteinase with Thrombospondin Motifs 4, 5, 7, and 12

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