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Logo of annrheumdAnnals of the Rheumatic DiseasesCurrent TOCInstructions for authors
Ann Rheum Dis. Feb 2003; 62(2): 100–107.
PMCID: PMC1754433

Angiopoietin-1 is expressed in the synovium of patients with rheumatoid arthritis and is induced by tumour necrosis factor α

Abstract

Objectives: To examine the potential role of the angiogenic growth factor angiopoietin-1 (Ang-1) in inflammatory arthritis.

Methods: Eighteen synovial tissue samples were obtained from 17 patients with a clinical diagnosis of rheumatoid arthritis (RA) and compared with six synovial tissue samples from six patients with osteoarthritis (OA). Ang-1 expression in synovial tissues was determined by immunohistochemistry and in situ hybridisation. Ang-1 mRNA and protein expression were also examined by northern blot analysis and enzyme linked immunosorbent assay (ELISA) in cultured synovial fibroblasts and human umbilical vein endothelial cells (HUVECs) before and after treatment with tumour necrosis factor (TNF)α.

Results: Ang-1 protein expression was detected by immunohistochemistry in 16/18 RA synovial tissue samples. Ang-1 protein was frequently observed in the synovial lining layer and in cells within the sublining synovial tissue, in both perivascular areas and in areas remote from vessels. In contrast, Ang-1 was only weakly detected in these sites in OA samples. Ang-1 mRNA and protein were also expressed in cultured synovial fibroblasts derived from patients with RA. In addition, induction of Ang-1 mRNA and protein was observed by northern blot analysis and ELISA after stimulation of RA synovial fibroblasts, but not HUVECs, with the proinflammatory cytokine TNFα.

Conclusions: Ang-1 mRNA and protein are expressed in the synovium of patients with RA, and are up regulated in synovial fibroblasts by TNFα. Ang-1 may therefore be an important regulator of angiogenesis in inflammatory arthritis.

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Selected References

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Figures and Tables

Figure 1
Immunohistochemical staining of Ang-1 in RA and OA synovial tissue. (A) Ang-1 protein is demonstrated in RA synovial tissue in cells in the synovial lining layer, in some endothelial cells, and in cells within subsynovial tissue. (B) Isotype matched ...
Figure 2
In situ hybridisation for Ang-1 and Ang-2 in rheumatoid synovium. Ang-1 in situ hybridisation in synovial tissue samples from patients with RA using the Ang-1 antisense (A, C–F) and sense (B) probes, demonstrating representative areas of mRNA ...
Figure 3
Northern blot analysis of Ang-1 and Ang-2 in cultured synovial fibroblasts and human umbilical endothelial cells. (A) Induction of Ang-1 mRNA expression in cultured human synovial fibroblasts in response to TNFα (10 ng/ml) at baseline (lane 1) ...
Figure 4
ELISA analysis of Ang-1 protein in culture media of RA synovial fibroblasts. Ang-1 protein was quantified in the culture media of synovial fibroblasts stimulated with TNFα (10 ng/ml) at 0, 4, 18, 24, and 30 hours in this representative experiment. ...

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