Article abstract

Nature Medicine 15, 1414 - 1420 (2009)
Published online: 8 November 2009 | doi:10.1038/nm.2050

Synovial fibroblasts spread rheumatoid arthritis to unaffected joints

Stephanie Lefèvre1, Anette Knedla1, Christoph Tennie1, Andreas Kampmann1, Christina Wunrau2, Robert Dinser1, Adelheid Korb3, Eva-Maria Schnäker4, Ingo H Tarner1, Paul D Robbins5, Christopher H Evans6, Henning Stürz7, Jürgen Steinmeyer8, Steffen Gay9, Jürgen Schölmerich10, Thomas Pap2, Ulf Müller-Ladner1 & Elena Neumann1

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.

  1. Department of Internal Medicine and Rheumatology, Justus-Liebig-University Giessen, Kerckhoff-Clinic, Bad Nauheim, Germany.
  2. Institute of Experimental Musculoskeletal Medicine, University Hospital Muenster, Muenster, Germany.
  3. Department of Internal Medicine D, Nephrology and Rheumatology, University Hospital Muenster, Muenster, Germany.
  4. Department of Dermatology, University Hospital Muenster, Muenster, Germany.
  5. Department of Microbiology and Molecular Genetics, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania, USA.
  6. Center for Molecular Orthopedics, Harvard Medical School, Boston, Massachusetts, USA.
  7. Department of Orthopedics and Orthopedic Surgery, University Hospital Giessen and Marburg, Giessen, Germany.
  8. Department of Orthopedics and Experimental Orthopedics, University Hospital Giessen and Marburg, Giessen, Germany.
  9. Center for Experimental Rheumatology, Zürich Center for Integrative Human Physiology, USZ, Zürich, Switzerland.
  10. Department of Internal Medicine I, University of Regensburg, Regensburg, Germany.

Correspondence to: Elena Neumann1 e-mail:


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