The Journal of Experimental Medicine
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Published 20 December 2004. doi:10.1084/jem.20041545
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 200, Number 12, 1673-1679
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Brief Definitive Report

 Cadherin-11 Provides Specific Cellular Adhesion between Fibroblast-like Synoviocytes

Xavier Valencia1, Jonathan M.G. Higgins1, Hans P. Kiener1, David M. Lee1, Theresa A. Podrebarac1, Christopher C. Dascher1, Gerald F.M. Watts1, Emiko Mizoguchi3, Barry Simmons2, Dhavalkumar D. Patel4, Atul K. Bhan3, and Michael B. Brenner1

1 Department of Medicine, Division of Rheumatology, Immunology, and Allergy
2 Department of Orthopedic Surgery, Brigham and Women's Hospital
3 Immunopathology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115
4 Department of Medicine, Division of Allergy and Immunology, Duke University Medical Center, Durham, NC 27710

Address correspondence to Michael B. Brenner, Dept. of Medicine, Div. of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Smith Bldg., Rm. 552, One Jimmy Fund Way, Boston, MA 02115. Phone: (617) 525-1000; Fax: (617) 525-1001; email: mbrenner{at}rics.bwh.harvard.edu

Cadherins are integral membrane proteins expressed in tissue-restricted patterns that mediate homophilic intercellular adhesion. During development, they orchestrate tissue morphogenesis and, in the adult, they determine tissue integrity and architecture. The synovial lining is a condensation of fibroblast-like synoviocytes (FLS) and macrophages one to three cells thick. These cells are embedded within the extracellular matrix, but the structure is neither an epithelium nor an endothelium. Previously, the basis for organization of the synovium into a tissue was unknown. Here, we cloned cadherin-11 from human rheumatoid arthritis (RA)-derived FLS. We developed L cell transfectants expressing cadherin-11, cadherin-11 fusion proteins, and anti–cadherin-11 mAb. Cadherin-11 was found to be expressed mainly in the synovial lining by immunohistologic staining of human synovium. FLS adhered to cadherin-11–Fc, and transfection of cadherin-11 conferred the formation of tissue-like sheets and lining-like structures upon fibroblasts in vitro. These findings support a key role for cadherin-11 in the specific adhesion of FLS and in synovial tissue organization and behavior in health and RA.

Key Words: synovium • synoviocyte • rheumatoid arthritis • cadherin • cell adhesion


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