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Inflammatory processes and elevated osteoclast activity chaperon atrophic non-union establishment in a murine model
BACKGROUND: Delayed bone healing, especially in long bones poses one of the biggest problems in orthopeadic and reconstructive surgery and causes tremendous costs every year. There is a need for exploring the causes in order to find an adequate therapy. Earlier investigations of human scaphoid non-u...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6909450/ https://www.ncbi.nlm.nih.gov/pubmed/31831031 http://dx.doi.org/10.1186/s12967-019-02171-4 |
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author | Wagner, Johannes M. Schmidt, Sonja V. Dadras, Mehran Huber, Julika Wallner, Christoph Dittfeld, Stephanie Becerikli, Mustafa Jaurich, Henriette Reinkemeier, Felix Drysch, Marius Lehnhardt, Marcus Behr, Björn |
author_facet | Wagner, Johannes M. Schmidt, Sonja V. Dadras, Mehran Huber, Julika Wallner, Christoph Dittfeld, Stephanie Becerikli, Mustafa Jaurich, Henriette Reinkemeier, Felix Drysch, Marius Lehnhardt, Marcus Behr, Björn |
author_sort | Wagner, Johannes M. |
collection | PubMed |
description | BACKGROUND: Delayed bone healing, especially in long bones poses one of the biggest problems in orthopeadic and reconstructive surgery and causes tremendous costs every year. There is a need for exploring the causes in order to find an adequate therapy. Earlier investigations of human scaphoid non-union revealed an elevated osteoclast activity, accompanied by upregulated levels of TGF-beta and RANKL. Interestingly, scaphoid non-union seemed to be well vascularized. METHODS: In the current study, we used a murine femur-defect model to study atrophic non unions over a time-course of 10 weeks. Different time points were chosen, to gather insights into the dynamic processes of non-union establishment. RESULTS: Histological analyses as well as western blots and qRT-PCR indicated enhanced osteoclast activity throughout the observation period, paralleled by elevated levels of TGF-beta, TNF-alpha, MMP9, MMP13 and RANKL, especially during the early phases of non-union establishment. Interestingly, elevated levels of these mediators decreased markedly over a period of 10 weeks, as inflammatory reaction during non-union establishment seemed to wear out. To our surprise, osteoblastogenesis seemed to be unaffected during early stages of non-union establishment. CONCLUSION: Taken together, we gained first insights into the establishment process of atrophic non unions, in which inflammatory processes accompanied by highly elevated osteoclast activity seem to play a leading role. |
format | Online Article Text |
id | pubmed-6909450 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-69094502019-12-19 Inflammatory processes and elevated osteoclast activity chaperon atrophic non-union establishment in a murine model Wagner, Johannes M. Schmidt, Sonja V. Dadras, Mehran Huber, Julika Wallner, Christoph Dittfeld, Stephanie Becerikli, Mustafa Jaurich, Henriette Reinkemeier, Felix Drysch, Marius Lehnhardt, Marcus Behr, Björn J Transl Med Research BACKGROUND: Delayed bone healing, especially in long bones poses one of the biggest problems in orthopeadic and reconstructive surgery and causes tremendous costs every year. There is a need for exploring the causes in order to find an adequate therapy. Earlier investigations of human scaphoid non-union revealed an elevated osteoclast activity, accompanied by upregulated levels of TGF-beta and RANKL. Interestingly, scaphoid non-union seemed to be well vascularized. METHODS: In the current study, we used a murine femur-defect model to study atrophic non unions over a time-course of 10 weeks. Different time points were chosen, to gather insights into the dynamic processes of non-union establishment. RESULTS: Histological analyses as well as western blots and qRT-PCR indicated enhanced osteoclast activity throughout the observation period, paralleled by elevated levels of TGF-beta, TNF-alpha, MMP9, MMP13 and RANKL, especially during the early phases of non-union establishment. Interestingly, elevated levels of these mediators decreased markedly over a period of 10 weeks, as inflammatory reaction during non-union establishment seemed to wear out. To our surprise, osteoblastogenesis seemed to be unaffected during early stages of non-union establishment. CONCLUSION: Taken together, we gained first insights into the establishment process of atrophic non unions, in which inflammatory processes accompanied by highly elevated osteoclast activity seem to play a leading role. BioMed Central 2019-12-12 /pmc/articles/PMC6909450/ /pubmed/31831031 http://dx.doi.org/10.1186/s12967-019-02171-4 Text en © The Author(s) 2019 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Wagner, Johannes M. Schmidt, Sonja V. Dadras, Mehran Huber, Julika Wallner, Christoph Dittfeld, Stephanie Becerikli, Mustafa Jaurich, Henriette Reinkemeier, Felix Drysch, Marius Lehnhardt, Marcus Behr, Björn Inflammatory processes and elevated osteoclast activity chaperon atrophic non-union establishment in a murine model |
title | Inflammatory processes and elevated osteoclast activity chaperon atrophic non-union establishment in a murine model |
title_full | Inflammatory processes and elevated osteoclast activity chaperon atrophic non-union establishment in a murine model |
title_fullStr | Inflammatory processes and elevated osteoclast activity chaperon atrophic non-union establishment in a murine model |
title_full_unstemmed | Inflammatory processes and elevated osteoclast activity chaperon atrophic non-union establishment in a murine model |
title_short | Inflammatory processes and elevated osteoclast activity chaperon atrophic non-union establishment in a murine model |
title_sort | inflammatory processes and elevated osteoclast activity chaperon atrophic non-union establishment in a murine model |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6909450/ https://www.ncbi.nlm.nih.gov/pubmed/31831031 http://dx.doi.org/10.1186/s12967-019-02171-4 |
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