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(American Journal of Pathology. 2006;168:1486-1499.)
© 2006 American Society for Investigative Pathology

Cadherin-11 Induces Rheumatoid Arthritis Fibroblast-Like Synoviocytes to Form Lining Layers in Vitro

Hans P. Kiener, David M. Lee, Sandeep K. Agarwal and Michael B. Brenner

From Brigham and Women’s Hospital and the Department of Medicine, Division of Rheumatology, Immunology, and Allergy, Harvard Medical School, Boston, Massachusetts

The synovial lining of diarthrodial joints is composed of a condensed network of synoviocytes that form an intact layer via cell-to-cell contacts with significant intercellular matrix spaces. However, the molecular basis for synovial lining formation and its structural integrity has not been previously defined. In this study, using a three-dimensional fibroblast-like synoviocyte in vitro organ culture system, we provide evidence that cadherin-11 expressed in fibroblast-like synoviocytes plays a determining role in establishing the synovial lining layer. Fibroblast-like synoviocytes that were grown in three-dimensional matrices demonstrated formation of a lining structure at the interface between the matrix and the fluid phase. Treatment of fibroblast-like synoviocyte organ cultures with a cadherin-11-Fc fusion protein efficiently abrogated lining layer organization. Moreover, because E-cadherin-expressing fibroblasts failed to organize a lining layer structure at the tissue boundary, this effect appears to be a distinct characteristic of fibroblasts expressing cadherin-11. We found that cadherin-11 mediated fibroblast-like synoviocyte cell-to-cell adhesion via formation of adherens junctions that were linked to and remodeled the actin cytoskeleton. Together, these studies implicate cadherin-11 in synovial tissue and lining layer formation and provide an in vitro system to model fibroblast-like synoviocyte behavior and function in organizing the synovial tissue.




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D. M. Lee, H. P. Kiener, S. K. Agarwal, E. H. Noss, G. F. M. Watts, O. Chisaka, M. Takeichi, and M. B. Brenner
Cadherin-11 in Synovial Lining Formation and Pathology in Arthritis
Science, February 16, 2007; 315(5814): 1006 - 1010.
[Abstract] [Full Text] [PDF]


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Copyright © 2006 by the American Society for Investigative Pathology.