gms | German Medical Science

47. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 33. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh), 29. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR)

04.09. - 07.09.2019, Dresden

Integrin α11β1 deficiency affects joint destructions in arthritic hTNFtg mice

Meeting Abstract

  • Kerstin Katharina Rauwolf - Universitätsklinikum Münster, Westfälische-Wilhelms-Universität, Münster, Institut für Experimentelle Muskuloskelettale Forschung, Münster
  • Adrian Deichsel - Universitätsklinikum Münster, Westfälische Wilhelms-Universität, Institut für Experimentelle Muskuloskelettale Medizin, 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. 47. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 33. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh), 29. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR). Dresden, 04.-07.09.2019. Düsseldorf: German Medical Science GMS Publishing House; 2019. DocET.28

doi: 10.3205/19dgrh148, urn:nbn:de:0183-19dgrh1488

Veröffentlicht: 8. Oktober 2019

© 2019 Rauwolf et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe http://creativecommons.org/licenses/by/4.0/.


Gliederung

Text

Background: Integrins are connectors between the extracellular matrix (ECM) and intracellular signalling pathways involved in the regulation of cellular proliferation, migration, tissue invasion, cytokine and MMP production – key mechanisms leading to joint destruction during rheumatoid arthritis (RA). In this context, integrin α11β1 (ITGA11) is of special interest, because it is mainly expressed in cellular adhesive structures of mesenchymal cells. In this project we investigated the role of ITGA11 in the development of joint destructions in hTNFtg mice, an animal model resembling the arthritic pathology of human RA.

Methods: ITGA11 expression levels in SF of wild type (wt) and arthritic hTNFtg mice were analysed by Western Blot (WB) and immunofluorescence as well as immunohistochemistry using paraffin-embedded hind paws. Furthermore, different ECM substrates and their influence on ITGA11 expression and its subcellular location as well as expression pattern of interaction partners (e.g. vinculin, paxillin and talin) were investigated using WB and immunofluorescence. In functional studies isolated SF of ITGA11-/- mice were analysed regarding to invasiveness using a modified TEER-Assay and to identify coating-dependent differences in migration and adhesion.

Furthermore, ITGA11-/- mice were interbred with hTNFtg mice and arthritis parameters and histomorphological changes of the offspring were analysed by evaluation of clinical symptoms, µCT imaging and histopathology.

Results: hTNFtg SF showed a coating-independent enrichment of focal adhesions with an increased and most prominent expression of ITGA11. Coatings such as collagen I or fibronectin resulted in different expression levels of vinculin, paxillin and talin, but any differences between wt and ITGA11-/- SF were detectable. Analyses of the functional assays showed a reduced proliferation rate and invasiveness of ITGA11-/- SF, an altered coating-dependent migration rate and adhesion capacity of ITGA11-/- SF in comparison to wt SF. In vivo evaluation of ITGA11-/-hTNFtg mice revealed a milder arthritis score and less cartilage and bone destructions compared to hTNFtg mice.

Conclusion: ITGA11 is significantly up-regulated in hTNFtg mice and is involved in the pathological processes of cartilage and bone destructions during RA.