Artikel
RNA-Seq based identification of factors involved in knee joint regeneration after induced osteoarthritis in 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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Matthias Geyer
- 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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Susann Junker
- 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: | 29. August 2016 |
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Gliederung
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Background: In mammals, damaged tissues are often replaced by fibrotic scar tissue, which might hamper proper organ function. In contrast, many urodele amphibians and reptiles are able to restore damaged organs or even lost appendages. We established the newt Notophthalmus viridescens as a model organism to study endogenous knee joint regeneration in adult vertebrates. In this model, osteoarthritis (OA) like symptoms including joint instability and luxation can be induced by surgical removal of articular cartilage or by intra-articular injection of matrix-degrading enzymes, e.g. collagenase. In treated animals, joint function is restored within 3 months.
Methods: OA was induced in newts either by intra-articular injection of collagenase, mono-iodoacetate or by surgical manipulation of articular cartilage. Alterations of gene expression during regeneration in the newt were identified by quantitative transcriptome analysis using Illumina® next-generation sequencing (NGS). Relevant molecular pathways guiding regeneration were analyzed in all OA models and key candidate genes were identified using public available databases. The expression pattern was verified by Real-Time PCR analyses. The expression on the protein level was evaluated by immunohistochemistry in newt tissues and compared to murine tissues in a related collagenase-induced OA model.
Results: Several matricellular proteins including TN-C and CCN family members as well as a large number of muscle-related proteins were found to be differentially regulated during knee joint regeneration, e.g. nebulin, tropomodulins and obscurin. Altered TN-C and CCN1 expression was confirmed by Real-Time PCR. TN-C was also found to be differentially expressed in a collagenase-induced murine OA model. In this model, CCN1 protein expression was detectable in chondrocytes and osteophytes.
Conclusion: Matricellular proteins are key players during regenerative and repair processes since they can affect cellular adhesion and guide migration of different cell types. Evaluation of novel proteins and signaling pathways might help to understand the underlying mechanisms guiding regeneration, especially as muscle regeneration seems to be a central feature in newt OA. These findings might help to identify new mechanisms of cartilage and bone regeneration which could be transferred to human OA.
