Karen M Doody, Stephanie M Stanford, Cristiano Sacchetti, Mattias N D Svensson, Charlotte H Coles, Nikolaos Mitakidis, William B Kiosses, Beatrix Bartok, Camille Fos, Esther Cory, Robert L Sah, Ru Liu-Bryan, David L Boyle, Heather A Arnett, Tomas Mustelin, Maripat Corr, Jeffrey D Esko, Michel L Tremblay, Gary S Firestein, A Radu Aricescu, Nunzio Bottini
Despite the availability of several therapies for rheumatoid arthritis (RA) that target the immune system, a large number of RA patients fail to achieve remission. Joint-lining cells, called fibroblast-like synoviocytes (FLS), become activated during RA and mediate joint inflammation and destruction of cartilage and bone. We identify RPTPσ, a transmembrane tyrosine phosphatase, as a therapeutic target for FLS-directed therapy. RPTPσ is reciprocally regulated by interactions with chondroitin sulfate or heparan sulfate containing extracellular proteoglycans in a mechanism called the proteoglycan switch...
May 20, 2015: Science Translational Medicine