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43. Kongress der Deutschen Gesellschaft für Rheumatologie, 29. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie, 25. Wissenschaftliche Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie

02.-05. September 2015, Bremen

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Integrin α11β1 mediates adhesion and migration in synovial fibroblasts during RA

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  • Kerstin Katharina Rauwolf - Universitätsklinikum Münster, Westfälische- Wilhelms- Universität, Münster, Institut für Experimentelle Muskuloskelettale Forschung, Münster
  • Denise Beckmann - Universitätsklinikum Münster, Westfälische Wilhelms-Universität, Institut für Experimentelle Muskuloskelettale Medizin, Münster
  • Uwe Hansen - Universitätsklinikum Münster, Westfälische- Wilhelms- Universität Münster, Institut für Experimentelle Muskuloskelettale Forschung, Münster
  • Daniel Kronenberg - Universitätsklinikum Münster, Westfälische- Wilhelms- Universität Münster, Institut für Experimentelle Muskuloskelettale Forschung, Münster
  • Donald Gullberg - Department of Biomedicine and Centre for Cancer Biomarkers, University of Bergen, Bergen, Norway
  • Thomas Pap - Universitätsklinikum Münster, Westfälische Wilhelms-Universität, Institut für Experimentelle Muskuloskelettale Medizin, Münster
  • Adelheid Korb-Pap - Universitätsklinikum Münster, Westfälische Wilhelms-Universität, Institut für Experimentelle Muskuloskelettale Medizin, Münster

Deutsche Gesellschaft für Rheumatologie. Deutsche Gesellschaft für Orthopädische Rheumatologie. Gesellschaft für Kinder- und Jugendrheumatologie. 43. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh); 29. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh); 25. wissenschaftliche Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR). Bremen, 02.-05.09.2015. Düsseldorf: German Medical Science GMS Publishing House; 2015. DocER.11

doi: 10.3205/15dgrh065, urn:nbn:de:0183-15dgrh0652

Published: September 1, 2015

© 2015 Rauwolf et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.

Outline

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Introduction: Integrins mediate cell-matrix interactions of synovial fibroblasts (SF) with cartilage during rheumatoid arthritis (RA) resulting in cartilage degradation and destruction. In this context, integrin α11β1 (ITGA11) is of special interest, because it is mainly expressed in cellular adhesive structures and its role in inflammatory arthritis is unknown.

Methods: ITGA11 expression levels in SF of wild type and arthritic hTNFtg mice were analysed by Western Blot (WB) and immunofluorescence as well as immunohistochemistry using paraffin-embedded hind paws. Furthermore different extracellular matrix substrates and their influence on ITGA11 expression and its subcellular location were investigated using WB, immunofluorescence and electric cell-substrate impedance sensing (ECIS). Next, we analysed isolated SF of ITGA11-/- mice in functional studies (proliferation assay, modified scratch assay and an cartilage attachment assay) to identify differences in migration and adhesion. Furthermore K/BxN serum was transferred into wt and ITGA11-/- mice for arthritis induction. The time course of clinical symptomatic was evaluated and verified by immunohistopathology.

To identify a correlation between integrin α11β1 and α2β1 expression, we investigated ITGA2 levels by WB and immunohistochemistry.

Results: hTNFtg SF showed an enrichment of focal adhesions with increased and most prominent expression of ITGA11. Furthermore, ITGA11-/- SF showed a modified cytoskeleton arrangement compared to wt SF. Analyses of the functional assays showed a reduced proliferation rate of ITGA11-/- SF, an altered coating-dependent migration rate and adhesion capacity of ITGA11-/- SF in comparison to wt SF and an altered cell-cell and cell-matrix interaction. K/BxN serum treated ITGA11-/- mice showed a more severe paw swelling and a reduced grip strength in comparison to wt mice. The expression of ITGA2 in ITGA11-/- SF showed a difference in comparison to the wt SF.

Conclusion: Integrin α11β1 is induced under inflammatory conditions and contributes to the migratory and adhesive capacity of SF.