Artikel
Tenascin-C in joint regeneration after induced osteoarthritis in the newt Notophthalmus viridescens
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Autoren
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Christiane Schoenfeld
- Justus-Liebig-Universität Gießen, Kerckhoff-Klinik GmbH, Rheumatologie u. klinische Immunologie, Osteologie, Physikalische Therapie, Bad Nauheim
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Sony Adhi Susanto
- Justus-Liebig Universität Gießen, Kerckhoff-Klinik GmbH, Rheumatologie u. klinische Immunologie, Osteologie, Physikalische Therapie, Bad Nauheim
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Carina Schreiyaeck
- Justus-Liebig Universität Gießen, Kerckhoff-Klinik GmbH, Rheumatologie u. klinische Immunologie, Osteologie, Physikalische Therapie, Bad Nauheim
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Matthias Geyer
- Justus-Liebig-Universität Gießen, Kerckhoff-Klinik GmbH, Rheumatologie u. klinische Immunologie, Osteologie, Physikalische Therapie, Bad Nauheim
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Uwe Lange
- Justus-Liebig-Universität Gießen, Kerckhoff-Klinik GmbH, Rheumatologie u. klinische Immunologie, Osteologie, Physikalische Therapie, Bad Nauheim
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Mario Looso
- Max-Planck-Institut für Herz- und Lungenforschung, Bad Nauheim
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Thomas Braun
- Max-Planck-Institut für Herz- und Lungenforschung, Bad Nauheim
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Elena Neumann
- Justus-Liebig-Universität Gießen, Kerckhoff-Klinik GmbH, Rheumatologie u. klinische Immunologie, Osteologie, Physikalische Therapie, Bad Nauheim
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Ulf Müller-Ladner
- Justus-Liebig-Universität Gießen, Kerckhoff-Klinik GmbH, Rheumatologie u. klinische Immunologie, Osteologie, Physikalische Therapie, Bad Nauheim
| Veröffentlicht: | 1. September 2015 |
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Gliederung
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Introduction: While tissue damage in mammals often results in fibrotic scar tissue formation, many urodele amphibians can perfectly repair damaged tissues or even lost extremities. We established the red-spotted newt Notophthalmus viridescens as a model organism to study endogenous knee joint regneration in adult vertebrates. After intra-articular injection of collagenase or surgical removal of articular cartilage the treated newts display osteoarthritis(OA)-like symptoms including joint instability and luxation. Joint functionality is completely restored after approximately 3 months. Since the underlying mechanisms guiding regeneration are only poorly understood, we want to identify key players driving knee joint regeneration using a high resolution gene analysis approach.
Methods: A newt-specific cDNA array was performed after surgically and collagenase-induced knee damage in newts. Dysregulated candidate genes were selected and verified on the mRNA level by real-time PCR. Protein expression levels were analysed by immunohistochemistry (IHC). Adhesion experiments in newt-derived cell lines and primary newt cells (chondrocytes/fibroblasts) with/without tenascin-C (TN-C) knockdown or on TN-C coated culture plates were performed.
Results: The microarray revealed that during the regenerative process several matricellular proteins including TN-C were upregulated (day 10, TN-C vs. control 22.4-fold in collagenase-induced OA, 15.6-fold in surgically induced OA). In untreated newt legs, IHC revealed TN-C protein expression in the periosteum. During the early phase of regeneration (day 10) TN-C was detectable at the injury site (surgically induced OA). At later stages (20 and 40 days after injury) TN-C expression was observed in regenerating tissues including chondrocytes of the articular cartilage. The adhesion experiments using the newt-derived cell line B1H1 showed that TN-C coating hat anti-adhesive properties (TN-C vs. control: 42% reduction). However, TN-C knockdown in newt cell lines and primary newt cells on collagen I coated culture plates had no effects on cellular adhesion.
Conclusion: TN-C plays a role during knee joint regeneration in the newt. Current studies will help to identify molecular pathways involved in the increased regenerative capacity unique for the newt. These findings might allow the development of new treatment options for human OA.
