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Science 315 (5814): 1006-1010

Copyright © 2007 by the American Association for the Advancement of Science

Cadherin-11 in Synovial Lining Formation and Pathology in Arthritis

David M. Lee,1 Hans P. Kiener,1 Sandeep K. Agarwal,1* Erika H. Noss,1* Gerald F. M. Watts,1* Osamu Chisaka,2 Masatoshi Takeichi,3 Michael B. Brenner1{dagger}

Abstract: The normal synovium forms a membrane at the edges of joints and provides lubrication and nutrients for the cartilage. In rheumatoid arthritis, the synovium is the site of inflammation, and it participates in an organized tissue response that damages cartilage and bone. We identified cadherin-11 as essential for the development of the synovium. Cadherin-11–deficient mice have a hypoplastic synovial lining, display a disorganized synovial reaction to inflammation, and are resistant to inflammatory arthritis. Cadherin-11 therapeutics prevent and reduce arthritis in mouse models. Thus, synovial cadherin-11 determines the behavior of synovial cells in their proinflammatory and destructive tissue response in inflammatory arthritis.

1 Department of Medicine and Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, 1 Jimmy Fund Way, Boston, MA 02115, USA.
2 Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Yoshida-honmachi, Kyoto 606-8501, Japan.
3 RIKEN Center for Developmental Biology, Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: mbrenner{at}rics.bwh.harvard.edu

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