Editors' ChoiceMEDICINE

Switching off arthritis

Science Signaling  26 May 2015:
Vol. 8, Issue 378, pp. ec138
DOI: 10.1126/scisignal.aac6243

In patients with rheumatoid arthritis (RA), joint-lining cells—fibroblast-like synoviocytes (FLS)—become activated and contribute to inflammation, as well as cartilage and bone destruction. FLS have the receptor protein tyrosine phosphatase RPTPσ. In neurons, the interaction of RPTPσ with different proteoglycans either inhibits or promotes axonal growth, a phenomenon called the “proteoglycan switch.” Doody et al. found that FLS also responded to proteoglycans and that an RPTPσ decoy protein blocked this switch in human cells and decreased FLS invasiveness and severity of arthritis in a mouse model of RA. Targeting this proteoglycan switch may add another option when treating patients with RA.

K. M. Doody, S. M. Stanford, C. Sacchetti, M. N. D. Svensson, C. H. Coles, N. Mitakidis, W. B. Kiosses, B. Bartok, C. Fos, E. Cory, R. L. Sah, R. Liu-Bryan, D. L. Boyle, H. A. Arnett, T. Mustelin, M. Corr, J. D. Esko, M. L. Tremblay, G. S. Firestein, A. R. Aricescu, N. Bottini, Targeting phosphatase-dependent proteoglycan switch for rheumatoid arthritis therapy. Sci. Transl. Med. 7, 288ra76 (2015). [Abstract]

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