Modulation of matrix metalloproteinase production by rheumatoid arthritis synovial fibroblasts after cadherin 11 engagement

✍ Scribed by Erika H. Noss; Sook Kyung Chang; Gerald F. M. Watts; Michael B. Brenner

• Book ID: 101650324
• Publisher: John Wiley and Sons
• Year: 2011
• Tongue: English
• Weight: 239 KB
• Volume: 63
• Category: Article
• ISSN: 0004-3591
• DOI: 10.1002/art.30630

✦ Synopsis

Objective. Cadherin 11 is a homophilic cell-to-cell adhesion molecule expressed on joint synovial fibroblasts. Absence of cadherin 11 in a mouse rheumatoid arthritis (RA) model led to striking reductions in cartilage erosion. Matrix metalloproteinases (MMPs) are enzymes expressed by synovial fibroblasts important for cartilage erosion. The objective of this study was to determine if synovial fibroblast MMP production is regulated by cadherin 11. Methods. To mimic cadherin 11 engagement, human RA synovial fibroblasts were stimulated with a chimeric construct consisting of the cadherin 11 extracellular domain linked to the human IgG1 Fc domain (Cad-11-Fc). Effects on MMP production were measured by enzyme-linked immunosorbent assay, quantitative reverse transcription-polymerase chain reaction analysis, and immunoblotting. Results. Human Cad-11-Fc up-regulated MMP-1 and MMP-3 protein production by RA synovial fibroblasts, both alone and in synergy with tumor necrosis factor ␣. This up-regulation required cell cadherin 11 engagement, since a mutant Cad-11-Fc with reduced