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, 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
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.
Conflict of interest statement
Competing interests: The authors have no competing interests.
Figures
![Figure 1. Migration of RASFs](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3678354/bin/nihms468594f1.jpg)
Figure 2. Migratory potential of RASFs
(a)…
Figure 2. Migratory potential of RASFs
(a) Invasion scores of cartilage after s.c., i.v., i.p.…
Figure 3. Migration and adhesion of RASF…
Figure 3. Migration and adhesion of RASF in vitro
(a) Several RASFs (black bars) were…
Figure 4. RASF-transmigration and inhibition in vitro
Figure 4. RASF-transmigration and inhibition in vitro
(a) RASFs showed an increased transmigratory and invasive…
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- Research Support, Non-U.S. Gov't
- Animals
- Arthritis, Rheumatoid / pathology*
- Cartilage / pathology
- Cartilage / physiopathology
- Cell Adhesion
- Cell Movement
- Disease Progression
- Extracellular Matrix
- Fibroblasts / pathology
- Humans
- Mice
- Mice, SCID
- Synovial Membrane / pathology*
- Synovial Membrane / physiopathology
- Transplantation, Heterologous
- Full Text Sources
- Other Literature Sources
- Medical
- Molecular Biology Databases
- Research Materials
![Figure 2. Migratory potential of RASFs](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3678354/bin/nihms468594f2.jpg)
![Figure 3. Migration and adhesion of RASF…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3678354/bin/nihms468594f3.jpg)
![Figure 4. RASF-transmigration and inhibition in vitro](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3678354/bin/nihms468594f4.jpg)
Source: PubMed