Cadherin-11 regulates synovial fibroblast behavior in health and disease

Cadherin adhesion molecules, structurally typified by their immunoglobulin-like extracellular (cadherin) domains rigidified as an extended chain by interdomain calcium binding, mediate cellular adhesion by binding a cadherin of the same type on an adjacent cell (homophilic adhesion). During embryonic development, cadherins provide a basis for cell sorting, aggregation and resultant tissue morphogenesis and they are thought to contribute to tissue maintenance postnatally. In tumors, cadherins have been implicated in tissue extension, migration and invasion. Knowing these processes are active in the synovium both at baseline and in the context of the hyperplastic and invasive synovial tissue in inflammatory arthritis, we hypothesized that a cadherin may play a role in regulating this tissue behavior. Using mouse models, we demonstrate that synovial tissue fibroblasts express cadherin-11. We find that cadherin-11 null mice display a hypoplastic synovial lining and display attenuated arthritic responses to K/BxN serum transfer arthritis. Moreover, we find a remarkable decrease in synovial pannus invasion into cartilage. These observations reveal a role for cadherin-11 in the molecular regulation of the organized behavior of the synovial fibroblast both in health and disease.