Cadherin 11 promotes invasive behavior of fibroblast-like synoviocytes.

Abstract

OBJECTIVE:

To define the expression pattern of cadherin 11 in the destructive pannus tissue of patients with rheumatoid arthritis, and to determine whether cadherin 11 expression in fibroblast-like synoviocytes controls their invasive capacity.

METHODS:

Cadherin 11 expression in rheumatoid synovial tissue was evaluated using immunohistochemistry. To examine the role of cadherin 11 in regulating the invasive behavior of fibroblast-like synoviocytes, we generated L cell clones expressing wild-type cadherin 11, mutant cadherin 11, and empty vector-transfected controls. The invasive capacity of L cell transfectants and cultured fibroblast-like synoviocytes treated with a blocking cadherin 11-Fc fusion protein or control immunoglobulin was determined in Matrigel invasion assays.

RESULTS:

Immunohistochemical analysis revealed that cadherin 11 is abundantly expressed in cells at the cartilage-pannus junction in rheumatoid synovitis. Assays to determine invasion demonstrated a 2-fold increased invasive capacity of cadherin 11-transfected L cells compared with L cells transfected with E-cadherin or control vector. The invasive behavior of L cells stably transfected with a cadherin 11 construct that lacked the juxtamembrane cytoplasmic domain was diminished to the level of vector control L cells. Furthermore, treatment with the cadherin 11-Fc fusion protein diminished the invasive capacity of fibroblast-like synoviocytes.

CONCLUSION:

The results of these in vitro studies implicate a role for cadherin 11 in promoting cell invasion and contribute insight into the invasive nature of fibroblast-like synoviocytes in chronic synovitis and rheumatoid arthritis.

• Authors: Hans P Kiener, Birgit Niederreiter, David M Lee, Esther Jimenez-Boj, Josef S Smolen, Michael B Brenner
• Journal: Arthritis and rheumatism (Arthritis Rheum) Vol. 60 Issue 5 Pg. 1305-10 (May 2009) ISSN: 0004-3591 [Print] United States
• PMID: 19404963 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Cadherins
• osteoblast cadherin

Topics

• Animals
• Arthritis, Rheumatoid (pathology)
• Cadherins (analysis, genetics, physiology)
• Fibroblasts (physiology)
• Humans
• Immunohistochemistry
• L Cells
• Mice
• Mutation
• Synovial Membrane (cytology, physiology)
• Synovitis (pathology)
• Transfection