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Complement receptors C5aR1 and C5aR2 act differentially during the early immune response after bone fracture but are similarly involved in bone repair
Severely injured patients frequently suffer compromised fracture healing because of systemic post-traumatic inflammation. An important trigger of the posttraumatic immune response is the complement anaphylatoxin C5a, which acts via two receptors, C5aR1 and C5aR2, expressed on immune and bone cells....
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5656620/ https://www.ncbi.nlm.nih.gov/pubmed/29070810 http://dx.doi.org/10.1038/s41598-017-14444-3 |
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author | Kovtun, Anna Bergdolt, Stephanie Hägele, Yvonne Matthes, Rebekka Lambris, John D. Huber-Lang, Markus Ignatius, Anita |
author_facet | Kovtun, Anna Bergdolt, Stephanie Hägele, Yvonne Matthes, Rebekka Lambris, John D. Huber-Lang, Markus Ignatius, Anita |
author_sort | Kovtun, Anna |
collection | PubMed |
description | Severely injured patients frequently suffer compromised fracture healing because of systemic post-traumatic inflammation. An important trigger of the posttraumatic immune response is the complement anaphylatoxin C5a, which acts via two receptors, C5aR1 and C5aR2, expressed on immune and bone cells. The blockade of C5a-mediated inflammation during the early inflammatory phase was demonstrated to improve fracture healing after severe injury. However, the distinct roles of the two complement receptors C5aR1 and C5aR2 in bone has to date not been studied. Here, we investigated bone turnover and regeneration in mice lacking either C5aR1 or C5aR2 in a model of isolated fracture and after severe injury, combining the fracture with an additional thoracic trauma. Both C5aR1(−/−) and C5aR2(−/−) mice displayed an increased bone mass compared to wild-type controls due to reduced osteoclast formation and increased osteoblast numbers, respectively. Following fracture, the inflammatory response was differently affected in these strains: It was decreased in C5aR1(−/−) mice but enhanced in C5aR2(−/−) mice. Both strains exhibited impaired fracture healing, disturbed osteoclastogenesis and delayed cartilage-to-bone transformation. Thus, our data suggest that C5aR1 and C5aR2 differentially regulate the immune response after fracture and are required for effective cartilage-to-bone transformation in the fracture callus and for undisturbed bone healing. |
format | Online Article Text |
id | pubmed-5656620 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-56566202017-10-31 Complement receptors C5aR1 and C5aR2 act differentially during the early immune response after bone fracture but are similarly involved in bone repair Kovtun, Anna Bergdolt, Stephanie Hägele, Yvonne Matthes, Rebekka Lambris, John D. Huber-Lang, Markus Ignatius, Anita Sci Rep Article Severely injured patients frequently suffer compromised fracture healing because of systemic post-traumatic inflammation. An important trigger of the posttraumatic immune response is the complement anaphylatoxin C5a, which acts via two receptors, C5aR1 and C5aR2, expressed on immune and bone cells. The blockade of C5a-mediated inflammation during the early inflammatory phase was demonstrated to improve fracture healing after severe injury. However, the distinct roles of the two complement receptors C5aR1 and C5aR2 in bone has to date not been studied. Here, we investigated bone turnover and regeneration in mice lacking either C5aR1 or C5aR2 in a model of isolated fracture and after severe injury, combining the fracture with an additional thoracic trauma. Both C5aR1(−/−) and C5aR2(−/−) mice displayed an increased bone mass compared to wild-type controls due to reduced osteoclast formation and increased osteoblast numbers, respectively. Following fracture, the inflammatory response was differently affected in these strains: It was decreased in C5aR1(−/−) mice but enhanced in C5aR2(−/−) mice. Both strains exhibited impaired fracture healing, disturbed osteoclastogenesis and delayed cartilage-to-bone transformation. Thus, our data suggest that C5aR1 and C5aR2 differentially regulate the immune response after fracture and are required for effective cartilage-to-bone transformation in the fracture callus and for undisturbed bone healing. Nature Publishing Group UK 2017-10-25 /pmc/articles/PMC5656620/ /pubmed/29070810 http://dx.doi.org/10.1038/s41598-017-14444-3 Text en © The Author(s) 2017 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Kovtun, Anna Bergdolt, Stephanie Hägele, Yvonne Matthes, Rebekka Lambris, John D. Huber-Lang, Markus Ignatius, Anita Complement receptors C5aR1 and C5aR2 act differentially during the early immune response after bone fracture but are similarly involved in bone repair |
title | Complement receptors C5aR1 and C5aR2 act differentially during the early immune response after bone fracture but are similarly involved in bone repair |
title_full | Complement receptors C5aR1 and C5aR2 act differentially during the early immune response after bone fracture but are similarly involved in bone repair |
title_fullStr | Complement receptors C5aR1 and C5aR2 act differentially during the early immune response after bone fracture but are similarly involved in bone repair |
title_full_unstemmed | Complement receptors C5aR1 and C5aR2 act differentially during the early immune response after bone fracture but are similarly involved in bone repair |
title_short | Complement receptors C5aR1 and C5aR2 act differentially during the early immune response after bone fracture but are similarly involved in bone repair |
title_sort | complement receptors c5ar1 and c5ar2 act differentially during the early immune response after bone fracture but are similarly involved in bone repair |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5656620/ https://www.ncbi.nlm.nih.gov/pubmed/29070810 http://dx.doi.org/10.1038/s41598-017-14444-3 |
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