The influence of M-CSF on fracture healing in a mouse model

The influence of M-CSF on fracture healing in a mouse model

Abstract Macrophage colony-stimulating factor 1 (M-CSF) is known to play a critical role during fracture repair e.g. by recruiting stem cells to the fracture site and impacting hard callus formation by stimulating osteoclastogenesis. The aim of this experiment was to study the impact of systemic M-C...

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Autores principales: Julia Starlinger, Kambiz Sarahrudi, Mathias Kecht, Florian Koerbler, Peter Pietschmann, Seyedhossein Aharinejad
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/bf08620a8f25416692cd86c223e2d4db
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spelling oai:doaj.org-article:bf08620a8f25416692cd86c223e2d4db2021-11-21T12:21:07ZThe influence of M-CSF on fracture healing in a mouse model10.1038/s41598-021-01673-w2045-2322https://doaj.org/article/bf08620a8f25416692cd86c223e2d4db2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-01673-whttps://doaj.org/toc/2045-2322Abstract Macrophage colony-stimulating factor 1 (M-CSF) is known to play a critical role during fracture repair e.g. by recruiting stem cells to the fracture site and impacting hard callus formation by stimulating osteoclastogenesis. The aim of this experiment was to study the impact of systemic M-CSF application and its effect on bony healing in a mouse model of femoral osteotomy. Doing so, we studied 61 wild type (wt) mice (18-week-old female C57BL/6) which were divided into three groups: (1) femoral osteotomy, (2) femoral osteotomy + stabilization with external fixator and (3) femoral osteotomy + stabilization with external fixator + systemic M-CSF application. Further, 12 op/op mice underwent femoral osteotomy and served as proof of concept. After being sacrificed at 28 days bony bridging was evaluated ex vivo with µCT, histological and biomechanical testing. Systemic M-CSF application impacted osteoclasts numbers, which were almost as low as found in op/op mice. Regarding callus size, the application of M-CSF in wt mice resulted in significantly larger calluses compared to wt mice without systemic M-CSF treatment. We further observed an anabolic effect of M-CSF application resulting in increased trabecular thickness compared to wt animals without additional M-CSF application. Systemic M-CSF application did not alter biomechanical properties in WT mice. The impact of M-CSF application in a mouse model of femoral osteotomy was oppositional to what we were expecting. While M-CSF application had a distinct anabolic effect on callus size as well as trabecular thickness, this on bottom line did not improve biomechanical properties. We hypothesize that in addition to the well-recognized negative effects of M-CSF on osteoclast numbers this seems to further downstream cause a lack of feedback on osteoblasts. Ultimately, continuous M-CSF application in the absence of co-stimulatory signals (e.g. RANKL) might overstimulate the hematopoietic linage in favor of tissue macrophages instead of osteoclasts.Julia StarlingerKambiz SarahrudiMathias KechtFlorian KoerblerPeter PietschmannSeyedhossein AharinejadNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Julia Starlinger
Kambiz Sarahrudi
Mathias Kecht
Florian Koerbler
Peter Pietschmann
Seyedhossein Aharinejad
The influence of M-CSF on fracture healing in a mouse model
description Abstract Macrophage colony-stimulating factor 1 (M-CSF) is known to play a critical role during fracture repair e.g. by recruiting stem cells to the fracture site and impacting hard callus formation by stimulating osteoclastogenesis. The aim of this experiment was to study the impact of systemic M-CSF application and its effect on bony healing in a mouse model of femoral osteotomy. Doing so, we studied 61 wild type (wt) mice (18-week-old female C57BL/6) which were divided into three groups: (1) femoral osteotomy, (2) femoral osteotomy + stabilization with external fixator and (3) femoral osteotomy + stabilization with external fixator + systemic M-CSF application. Further, 12 op/op mice underwent femoral osteotomy and served as proof of concept. After being sacrificed at 28 days bony bridging was evaluated ex vivo with µCT, histological and biomechanical testing. Systemic M-CSF application impacted osteoclasts numbers, which were almost as low as found in op/op mice. Regarding callus size, the application of M-CSF in wt mice resulted in significantly larger calluses compared to wt mice without systemic M-CSF treatment. We further observed an anabolic effect of M-CSF application resulting in increased trabecular thickness compared to wt animals without additional M-CSF application. Systemic M-CSF application did not alter biomechanical properties in WT mice. The impact of M-CSF application in a mouse model of femoral osteotomy was oppositional to what we were expecting. While M-CSF application had a distinct anabolic effect on callus size as well as trabecular thickness, this on bottom line did not improve biomechanical properties. We hypothesize that in addition to the well-recognized negative effects of M-CSF on osteoclast numbers this seems to further downstream cause a lack of feedback on osteoblasts. Ultimately, continuous M-CSF application in the absence of co-stimulatory signals (e.g. RANKL) might overstimulate the hematopoietic linage in favor of tissue macrophages instead of osteoclasts.
format article
author Julia Starlinger
Kambiz Sarahrudi
Mathias Kecht
Florian Koerbler
Peter Pietschmann
Seyedhossein Aharinejad
author_facet Julia Starlinger
Kambiz Sarahrudi
Mathias Kecht
Florian Koerbler
Peter Pietschmann
Seyedhossein Aharinejad
author_sort Julia Starlinger
title The influence of M-CSF on fracture healing in a mouse model
title_short The influence of M-CSF on fracture healing in a mouse model
title_full The influence of M-CSF on fracture healing in a mouse model
title_fullStr The influence of M-CSF on fracture healing in a mouse model
title_full_unstemmed The influence of M-CSF on fracture healing in a mouse model
title_sort influence of m-csf on fracture healing in a mouse model
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/bf08620a8f25416692cd86c223e2d4db
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