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42. Kongress der Deutschen Gesellschaft für Rheumatologie, 28. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie, 24. Wissenschaftliche Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie

17.-20. September 2014, Düsseldorf

Joint regeneration after artificially induced osteoarthritis in the red-spotted newt Notophthalmus viridescens

Meeting Abstract

  • Christiane Schoenfeld - Justus-Liebig-Universität Gießen, Rheumatologie u. klinische Immunologie, Osteologie, Physikalische Therapie, Bad Nauheim
  • Sony Adhi Susanto - Justus-Liebig Universität Gießen, Kerckhoff-Klinik GmbH, Rheumatologie u. klinische Immunologie, Osteologie, Physikalische Therapie, Bad Nauheim
  • Matthias Geyer - Justus-Liebig Universität Gießen, Kerckhoff-Klinik GmbH, Rheumatologie u. klinische Immunologie, Osteologie, Physikalische Therapie, Bad Nauheim
  • Carina Schreiyaeck - Justus-Liebig Universität Gießen, Kerckhoff-Klinik GmbH, Rheumatologie u. klinische Immunologie, Osteologie, Physikalische Therapie, Bad Nauheim
  • Uwe Lange - Justus-Liebig Universität Gießen, Kerckhoff-Klinik GmbH, Rheumatologie u. klinische Immunologie, Osteologie, Physikalische Therapie, Bad Nauheim
  • Mario Looso - Max-Planck-Institut für Herz- und Lungenforschung, Bad Nauheim
  • Thomas Braun - Max-Planck-Institut für Herz- und Lungenforschung, Bad Nauheim
  • Ulf Müller-Ladner - Justus-Liebig Universität Gießen, Kerckhoff-Klinik GmbH, Rheumatologie u. klinische Immunologie, Osteologie, Physikalische Therapie, Bad Nauheim
  • Elena Neumann - Justus-Liebig Universität Gießen, Kerckhoff-Klinik GmbH, Rheumatologie u. klinische Immunologie, Osteologie, Physikalische Therapie, Bad Nauheim

Deutsche Gesellschaft für Rheumatologie. Deutsche Gesellschaft für Orthopädische Rheumatologie. Gesellschaft für Kinder- und Jugendrheumatologie. 42. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh); 28. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh); 24. wissenschaftliche Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR). Düsseldorf, 17.-20.09.2014. Düsseldorf: German Medical Science GMS Publishing House; 2014. DocER.07

doi: 10.3205/14dgrh074, urn:nbn:de:0183-14dgrh0745

Published: September 12, 2014

© 2014 Schoenfeld et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.


Outline

Text

Background: When tissue or organ damage occurs in mammals, damaged tissue often is not substituted with functional but fibrotic scar tissue. Depending on the severity of tissue damage and subsequent scar tissue formation, proper organ function might be hampered. In contrast, many urodele amphibians have a remarkable capability to restore damaged organs or even lost appendages. The regenerated organ will almost perfectly resemble the lost one, both in function and size. In our working group, the red-spotted newt Notophthalmus viridescens has been established as a model organism to study endogenous knee joint regeneration in adult vertebrates. After either intra-articular injection of collagenase or surgical removal of articular cartilage, treated newts display osteoarthritis-(OA)-like symptoms, including joint instability and luxation. In contrast to mammals, joint function was completely restored in treated animals after approximately 3 months. However, the underlying mechanisms guiding this regenerative process are poorly understood.

Methods: To identify key players involved in knee joint regeneration, a cDNA array derived from regenerating newt myocardium was carried out after surgically and collagenase-induced knee damage in newts. Candidate genes were selected and analyzed on the mRNA level by Real Time PCR and on the protein level by immunohistochemistry. siRNA against newt tenascin-C (TN-C) were designed and used for knockdown in newt cells (cell lines, primary cells).

Results: Several matricellular proteins including TN-C, periostin and osteonectin/SPARC were found to be upregulated in both newt OA models. TN-C displayed the strongest upregulation during the regenerative process. The TN-C upregulation could be verified by Real Time PCR. Based on immunohistochemical analysis, TN-C expression was detectable in the periosteum during the early phase of regeneration. At later time points (>40 days after injury) TN-C expression was also found in regenerating cartilage. In vitro knock-down in newt-derived cell lines and primary newt cells (chondrocytes/fibroblasts) has been established and effects of this knockdown will be further evaluated.

Conclusion: TN-C plays a role during the early regenerative process after OA-like joint injury in the newt. Ongoing in vitro siRNA knockdown experiments can help to identify molecular pathways guiding regeneration. Findings might help to develop new treatment options of human OA.