Differential expression of the angiogenic Tie receptor family in arthritic and normal synovial tissue

Shiva Shahrara, Michael V. Volin, Matthew A. Connors, G. Kenneth Haines, Alisa E. Koch

Research output: Contribution to journalReview articlepeer-review

103 Scopus citations

Abstract

Angiopoietins (Ang) are vascular endothelial cell-specific growth factors that play important roles principally during the later stages of angiogenesis. We have compared the distribution of the receptor tyrosine kinase (Tie) and the Ang ligands in synovial tissues from normal subjects and those with rheumatoid arthritis (RA) and osteoarthritis (OA). Immunohistochemical analysis was used to determine the expression of Ang-1, Ang-2, Tie1 and Tie2 in synovial tissue of normal subjects and those with RA and OA. Ang-1, Ang-2, Tie1 and Tie2 mRNA and protein expression were quantified in synovial tissues and RA synovial tissue fibroblasts with real-time reverse transcription polymerase chain reaction and western blot analysis. In RA, Ang-1 positive immunostaining on lining cells, macrophages and endothelial cells was significantly higher than in OA and normal synovial tissue. The expression pattern of Ang-2 in synovial tissue was similar in RA and OA, whereas the Ang-2 expression was low in normal tissue. Synovial tissue from subjects with RA and OA showed a significant upregulation of Tie1 on lining cells, macrophages and endothelial cells compared to that from normal subjects. Tie2 was significantly upregulated in the RA and OA synovial tissue lining cells, macrophages and smooth muscle cells compared to normal synovial tissue. Generally Ang-1, Ang-2, Tie1 and Tie2 mRNA levels were higher in RA synovial tissue compared to normal and OA synovial tissues, and RA synovial tissue fibroblasts. Western blot analysis also demonstrated greater Tie1 and Tie2 protein expression in RA and OA synovial tissue compared to RA synovial tissue fibroblasts. In conclusion, the dominance of Ang-1 mRNA and protein expression over Ang-2 is in agreement with an active neovascularization in RA synovial tissue.

Original languageEnglish
Pages (from-to)201-208
Number of pages8
JournalArthritis Research
Volume4
Issue number3
DOIs
StatePublished - 2002
Externally publishedYes

Keywords

  • Angiopoietin
  • Rheumatoid arthritis
  • Tie receptor expression
  • mRNA

Fingerprint

Dive into the research topics of 'Differential expression of the angiogenic Tie receptor family in arthritic and normal synovial tissue'. Together they form a unique fingerprint.

Cite this