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Open Access 01-12-2016 | Research

C5aR inhibition in the early inflammatory phase does not affect bone regeneration in a model of uneventful fracture healing

Authors: Christian Ehrnthaller, Markus Huber-Lang, Anna Kovtun, Anna Elise Rapp, Julia Kemmler, Florian Gebhard, Anita Ignatius

Published in: European Journal of Medical Research | Issue 1/2016

Abstract

Background

Recent studies were able to demonstrate involvement of the complement cascade in bone biology. Further studies analyzed the role of complement in traumatic injuries and demonstrated negative effects after excessive systemic activation of the inflammatory response with early abrogation of complement activation after application of a C5aR-antagonist exerting beneficial effects upon bone regeneration. In contrast, own fracture healing experiments with complement-deficient animals implied a crucial role of the complement cascade for sufficient fracture healing.

Methods

To analyze the effect of a short abrogation of the complement system in the local process of fracture healing, a fracture healing experiment with wild-type mice (C57BL6), femoral osteotomy, consecutive external fixation for 21 days and blockade of the early complement activation (C5aRA) directly after trauma and after 12 h was performed. Control animals received a peptide without any biological effects. After 1–3 days, the inflammatory response was monitored with IL-6 immunostaining, serum analyses of C5a and after 3 days with histological evaluation of PMN. Fracture healing was examined with biomechanical, radiological and histological methods after 21 days.

Results

While a decrease of the early inflammatory response was seen on day 1 of the C5aRA-treated group regarding immunostaining for IL-6 and after 3 days in the histological evaluation of PMN, no significant differences were demonstrated between both experimental groups after 21 days in the biomechanical, radiological and histological evaluation.

Conclusions

The present results demonstrate that the short-term inhibition of complement activation immediately after fracture does not significantly affect bone regeneration in an experimental model of regular fracture healing. Whereas other studies demonstrated that the early posttraumatic blockade of the C5aR improves fracture healing in a scenario of combined trauma, the present findings implicate that the same treatment has no effect in uneventful bone healing.

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Title: C5aR inhibition in the early inflammatory phase does not affect bone regeneration in a model of uneventful fracture healing
Authors: Christian Ehrnthaller
Markus Huber-Lang
Anna Kovtun
Anna Elise Rapp
Julia Kemmler
Florian Gebhard
Anita Ignatius
Publication date: 01-12-2016
Publisher: BioMed Central
Published in: European Journal of Medical Research / Issue 1/2016
Electronic ISSN: 2047-783X
DOI: https://doi.org/10.1186/s40001-016-0236-7

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C5aR inhibition in the early inflammatory phase does not affect bone regeneration in a model of uneventful fracture healing

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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