Synovial fibroblasts spread rheumatoid arthritis to unaffected joints

Stephanie Lefèvre, Anette Knedla, Christoph Tennie, Andreas Kampmann, Christina Wunrau, Robert Dinser, Adelheid Korb, Eva Maria Schnäker, Ingo H. Tarner, Paul D. Robbins, Christopher H. Evans, Henning Stürz, Jürgen Steinmeyer, Steffen Gay, Jürgen Schölmerich, Thomas Pap, Ulf Müller-Ladner, Elena Neumann

Research output: Contribution to journalArticlepeer-review

372 Scopus citations

Abstract

Active rheumatoid arthritis originates from few joints but subsequently affects the majority of joints. Thus far, the pathways of the progression of the disease are largely unknown. As rheumatoid arthritis synovial fibroblasts (RASFs) which can be found in RA synovium are key players in joint destruction and are able to migrate in vitro, we evaluated the potential of RASFs to spread the disease in vivo. To simulate the primary joint of origin, we implanted healthy human cartilage together with RASFs subcutaneously into severe combined immunodeficient (SCID) mice. At the contralateral flank, we implanted healthy cartilage without cells. RASFs showed an active movement to the naive cartilage via the vasculature independent of the site of application of RASFs into the SCID mouse, leading to a marked destruction of the target cartilage. These findings support the hypothesis that the characteristic clinical phenomenon of destructive arthritis spreading between joints is mediated, at least in part, by the transmigration of activated RASFs.

Original languageEnglish (US)
Pages (from-to)1414-1420
Number of pages7
JournalNature Medicine
Volume15
Issue number12
DOIs
StatePublished - Dec 2009

Bibliographical note

Funding Information:
This study was funded by a start-up grant of the German Society of Rheumatology, by research grants of the German Research Foundation (Deutsche Forschungsgemeinschaft: NE1174/3-1, MU1383/14-1, FOR 696), by the Swiss National Fond 32000-116842 and by the Sixth Framework Programme Autocure and Seventh Framework Programme Masterswitch of the EU initiatives. We wish to thank S. Benninghoff, B. Riepl, S. Brückmann and C. Schreiyäck for technical assistance.

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