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C5aR‐antagonist significantly reduces the deleterious effect of a blunt chest trauma on fracture healing
Author(s) -
Recknagel Stefan,
Bindl Ronny,
Kurz Julian,
Wehner Tim,
Schoengraf Philipp,
Ehrnthaller Christian,
Qu Hongchang,
Gebhard Florian,
HuberLang Markus,
Lambris John D.,
Claes Lutz,
Ignatius Anita
Publication year - 2012
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.21561
Subject(s) - bone healing , medicine , blunt , antagonist , inflammation , systemic inflammation , surgery , receptor
Confirming clinical evidence, we recently demonstrated that a blunt chest trauma considerably impaired fracture healing in rats, possibly via the interaction of posttraumatic systemic inflammation with local healing processes, the underlying mechanisms being unknown. An important trigger of systemic inflammation is the complement system, with the potent anaphylatoxin C5a. Therefore, we investigated whether the impairment of fracture healing by a severe trauma resulted from systemically activated complement. Rats received a blunt chest trauma and a femur osteotomy stabilized with an external fixator. To inhibit the C5a‐dependent posttraumatic systemic inflammation, half of the rats received a C5aR‐antagonist intravenously immediately and 12 h after the thoracic trauma. Compared to the controls (control peptide), the treatment with the C5aR‐antagonist led to a significantly increased flexural rigidity (three‐point‐bending test), an improved bony bridging of the fracture gap, and a slightly larger and qualitatively improved callus (µCT, histomorphometry) after 35 days. In conclusion, immunomodulation by a C5aR‐antagonist could abolish the deleterious effects of a thoracic trauma on fracture healing, possibly by influencing the function of inflammatory and bone cells locally at the fracture site. C5a could possibly represent a target to prevent delayed bone healing in patients with severe trauma. © 2011 Orthopaedic Research Society. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:581–586, 2012