Editors' ChoiceInflammatory Disease

Spreading Aches

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Science Translational Medicine  18 Nov 2009:
Vol. 1, Issue 7, pp. 7ec25
DOI: 10.1126/scitranslmed.3000608

Rheumatoid arthritis (RA) is a long-term inflammatory disease that begins in a single joint and its surrounding tissues, but eventually spreads to destroy most of the joints in the body. This process has been suggested to be a result of circulation of factors or one of the numerous cell types involved in joint destruction, yet no conclusive data from animal models of arthritis has so far illuminated the pathway of disease progression. Now, Lefevre et al. show that a subset of fibroblasts in the synovial fluid surrounding an RA joint (RASFs) actively participate in joint destruction, but also migrate to healthy unaffected joints and trigger deterioration of the cartilage. Using a SCID mouse model, the authors implanted a human cartilage sponge with human RASFs subcutaneously in one flank, and implanted a cartilage sponge without RASFs on the contralateral flank and showed that the RASFs could migrate through the mouse body, invade, and begin to destroy the contralateral human cartilage implant in vivo. The migratory ability of RASFs was not due to short-range wounding since RASFs injected subcutaneously, intraperitoneally, and intravenously could also destroy implanted cartilage. Their long-distance effects did depend on neovascularization within the implants. Interestingly, the authors were able to show that, in addition to the human cartilage implants being affected by injected RASFs, RASFs were able to circulate long distances in mouse blood, filter through the spleen, and invade and attach to cartilage in healthy mouse joints.

S. Lefevre et al., Synovial fibroblasts spread rheumatoid arthritis to unaffected joints. Nat. Med. 8 November 2009 (10.1038/nm.2050) [Abstract]

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