Title

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

UMMS Affiliation

Department of Medicine, Division of Rheumatology

Date

2-2003

Document Type

Article

Medical Subject Headings

Angiogenesis Inducing Agents; Angiopoietin-1; Angiopoietin-2; Arthritis, Rheumatoid; Blotting, Northern; Culture Techniques; Fibroblasts; Humans; Immunoenzyme Techniques; In Situ Hybridization; Interleukin-1; Membrane Glycoproteins; Osteoarthritis; RNA, Messenger; Synovial Membrane; Tumor Necrosis Factor-alpha

Disciplines

Musculoskeletal Diseases | Rheumatology | Skin and Connective Tissue Diseases

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)alpha.

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 TNF alpha.

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

Rights and Permissions

Citation: Ann Rheum Dis. 2003 Feb;62(2):100-7. doi:10.1136/ard.62.2.100. Link to article on publisher's website

Comments

At the time of publication, Ellen Gravallese was not yet affiliated with the University of Massachusetts Medical School

Related Resources

Link to Article in PubMed

PubMed ID

12525377