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Cadherin-11 in Synovial Lining Formation and Pathology in Arthritis
David M. Lee,1Hans P. Kiener,1Sandeep K. Agarwal,1*Erika H. Noss,1*Gerald F. M. Watts,1*Osamu Chisaka,2Masatoshi Takeichi,3Michael B. Brenner1
The normal synovium forms a membrane at the edges of jointsand provides lubrication and nutrients for the cartilage. Inrheumatoid arthritis, the synovium is the site of inflammation,and it participates in an organized tissue response that damagescartilage and bone. We identified cadherin-11 as essential forthe development of the synovium. Cadherin-11deficientmice have a hypoplastic synovial lining, display a disorganizedsynovial reaction to inflammation, and are resistant to inflammatoryarthritis. Cadherin-11 therapeutics prevent and reduce arthritisin mouse models. Thus, synovial cadherin-11 determines the behaviorof synovial cells in their proinflammatory and destructive tissueresponse 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.
To whom correspondence should be addressed. E-mail: mbrenner{at}rics.bwh.harvard.edu
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