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Local Wnt3a treatment restores bone regeneration in large osseous defects after surgical debridement of osteomyelitis

ABSTRACT: Impaired bone homeostasis caused by osteomyelitis provokes serious variations in the bone remodeling process, thereby involving multiple inflammatory cytokines to activate bone healing. We have previously established a mouse model for post-traumatic osteomyelitis and studied bone regenerat...

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Autores principales: Wagner, Johannes Maximilian, Reinkemeier, Felix, Dadras, Mehran, Wallner, Christoph, Huber, Julika, Sogorski, Alexander, Sacher, Maxi, Schmidt, Sonja, Drysch, Marius, Dittfeld, Stephanie, Becerikli, Mustafa, Becker, Kathrin, Rauch, Nicole, Lehnhardt, Marcus, Behr, Björn
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8526481/
https://www.ncbi.nlm.nih.gov/pubmed/32424558
http://dx.doi.org/10.1007/s00109-020-01924-9
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author Wagner, Johannes Maximilian
Reinkemeier, Felix
Dadras, Mehran
Wallner, Christoph
Huber, Julika
Sogorski, Alexander
Sacher, Maxi
Schmidt, Sonja
Drysch, Marius
Dittfeld, Stephanie
Becerikli, Mustafa
Becker, Kathrin
Rauch, Nicole
Lehnhardt, Marcus
Behr, Björn
author_facet Wagner, Johannes Maximilian
Reinkemeier, Felix
Dadras, Mehran
Wallner, Christoph
Huber, Julika
Sogorski, Alexander
Sacher, Maxi
Schmidt, Sonja
Drysch, Marius
Dittfeld, Stephanie
Becerikli, Mustafa
Becker, Kathrin
Rauch, Nicole
Lehnhardt, Marcus
Behr, Björn
author_sort Wagner, Johannes Maximilian
collection PubMed
description ABSTRACT: Impaired bone homeostasis caused by osteomyelitis provokes serious variations in the bone remodeling process, thereby involving multiple inflammatory cytokines to activate bone healing. We have previously established a mouse model for post-traumatic osteomyelitis and studied bone regeneration after sufficient debridement. Moreover, we could further characterize the postinfectious inflammatory state of bony defects after debridement with elevated osteoclasts and decreased bone formation despite the absence of bacteria. In this study, we investigated the positive effects of Wnt-pathway modulation on bone regeneration in our previous established mouse model. This was achieved by local application of Wnt3a, a recombinant activator of the canonical Wnt-pathway. Application of Wnt3a could enhance new bone formation, which was verified by histological and μ-CT analysis. Moreover, histology and western blots revealed enhanced osteoblastogenesis and downregulated osteoclasts in a RANKL-dependent manner. Further analysis of Wnt-pathway showed downregulation after bone infections were reconstituted by application of Wnt3a. Interestingly, Wnt-inhibitory proteins Dickkopf 1 (DKK1), sclerostin, and secreted frizzled protein 1 (sFRP1) were upregulated simultaneously to Wnt-pathway activation, indicating a negative feedback for active form of Beta-catenin. In this study, we could demonstrate enhanced bone formation in defects caused by post-traumatic osteomyelitis after Wnt3a application. KEY MESSAGES: Osteomyelitis decreases bone regeneration. Wnt3a restores bone healing after infection. Canonical Wnt-pathway activation with negative feedback. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00109-020-01924-9) contains supplementary material, which is available to authorized users.
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spelling pubmed-85264812021-11-04 Local Wnt3a treatment restores bone regeneration in large osseous defects after surgical debridement of osteomyelitis Wagner, Johannes Maximilian Reinkemeier, Felix Dadras, Mehran Wallner, Christoph Huber, Julika Sogorski, Alexander Sacher, Maxi Schmidt, Sonja Drysch, Marius Dittfeld, Stephanie Becerikli, Mustafa Becker, Kathrin Rauch, Nicole Lehnhardt, Marcus Behr, Björn J Mol Med (Berl) Original Article ABSTRACT: Impaired bone homeostasis caused by osteomyelitis provokes serious variations in the bone remodeling process, thereby involving multiple inflammatory cytokines to activate bone healing. We have previously established a mouse model for post-traumatic osteomyelitis and studied bone regeneration after sufficient debridement. Moreover, we could further characterize the postinfectious inflammatory state of bony defects after debridement with elevated osteoclasts and decreased bone formation despite the absence of bacteria. In this study, we investigated the positive effects of Wnt-pathway modulation on bone regeneration in our previous established mouse model. This was achieved by local application of Wnt3a, a recombinant activator of the canonical Wnt-pathway. Application of Wnt3a could enhance new bone formation, which was verified by histological and μ-CT analysis. Moreover, histology and western blots revealed enhanced osteoblastogenesis and downregulated osteoclasts in a RANKL-dependent manner. Further analysis of Wnt-pathway showed downregulation after bone infections were reconstituted by application of Wnt3a. Interestingly, Wnt-inhibitory proteins Dickkopf 1 (DKK1), sclerostin, and secreted frizzled protein 1 (sFRP1) were upregulated simultaneously to Wnt-pathway activation, indicating a negative feedback for active form of Beta-catenin. In this study, we could demonstrate enhanced bone formation in defects caused by post-traumatic osteomyelitis after Wnt3a application. KEY MESSAGES: Osteomyelitis decreases bone regeneration. Wnt3a restores bone healing after infection. Canonical Wnt-pathway activation with negative feedback. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00109-020-01924-9) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2020-05-18 2020 /pmc/articles/PMC8526481/ /pubmed/32424558 http://dx.doi.org/10.1007/s00109-020-01924-9 Text en © The Author(s) 2020, corrected publication 2021 https://creativecommons.org/licenses/by/4.0/Open Access This 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/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Article
Wagner, Johannes Maximilian
Reinkemeier, Felix
Dadras, Mehran
Wallner, Christoph
Huber, Julika
Sogorski, Alexander
Sacher, Maxi
Schmidt, Sonja
Drysch, Marius
Dittfeld, Stephanie
Becerikli, Mustafa
Becker, Kathrin
Rauch, Nicole
Lehnhardt, Marcus
Behr, Björn
Local Wnt3a treatment restores bone regeneration in large osseous defects after surgical debridement of osteomyelitis
title Local Wnt3a treatment restores bone regeneration in large osseous defects after surgical debridement of osteomyelitis
title_full Local Wnt3a treatment restores bone regeneration in large osseous defects after surgical debridement of osteomyelitis
title_fullStr Local Wnt3a treatment restores bone regeneration in large osseous defects after surgical debridement of osteomyelitis
title_full_unstemmed Local Wnt3a treatment restores bone regeneration in large osseous defects after surgical debridement of osteomyelitis
title_short Local Wnt3a treatment restores bone regeneration in large osseous defects after surgical debridement of osteomyelitis
title_sort local wnt3a treatment restores bone regeneration in large osseous defects after surgical debridement of osteomyelitis
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8526481/
https://www.ncbi.nlm.nih.gov/pubmed/32424558
http://dx.doi.org/10.1007/s00109-020-01924-9
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