Synovial cadherin-11

Cadherin-11 is a homophilic adhesion molecule that is expressed on fibroblast-like synoviocytes. To investigate a role for cadherin-11 in modulating synovial function, we have examined the synovial architecture and inflammatory responses in cadherin-11 mutant mice. We find these mice display a hypoplastic synovial lining with decreased cellular condensation and reduced extracellular matrix deposition. When challenged with arthritogenic serum in the KRN anti-GPI antibody-induced arthritis model in mice, cadherin-11-deficient animals display resistance to arthritis development. In animals that do develop detectable swelling and inflammation, there is a noted absence of cartilage damage, compared with wild-type animals with arthritis. Moreover, the architecture of the synovial response to inflammation is disorganized. In contrast to wild-type arthritic mice in which the synovial lining undergoes marked hyperplasia, the cadherin-11-deficient synovial reaction lacks a clearly detectable lining layer and shows a disorganized random inflammatory reaction. These results support the concept that fibroblast-like synoviocytes are direct participants in the highly orchestrated synovial reaction that occurs in inflammatory arthritis. Furthermore, these results reveal a role for synovial cadherin-11 in regulating synovial fibroblast function both in the healthy state and in the pathologic context of inflammatory arthritis.