C5aR-antagonist significantly reduces the deleterious effect of a blunt chest trauma on fracture healing

J Orthop Res. 2012 Apr;30(4):581-6. doi: 10.1002/jor.21561. Epub 2011 Sep 15.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomechanical Phenomena / physiology
  • Complement C5a / antagonists & inhibitors
  • Complement C5a / immunology
  • Disease Models, Animal
  • Femoral Fractures / diagnostic imaging
  • Femoral Fractures / immunology*
  • Femoral Fractures / physiopathology
  • Fracture Healing / drug effects*
  • Fracture Healing / immunology
  • Inflammation / complications
  • Inflammation / drug therapy
  • Inflammation / physiopathology
  • Male
  • Osteotomy
  • Peptides, Cyclic / pharmacology*
  • Rats
  • Rats, Wistar
  • Receptor, Anaphylatoxin C5a / antagonists & inhibitors*
  • Receptor, Anaphylatoxin C5a / immunology
  • Thoracic Injuries / immunology*
  • Thoracic Injuries / physiopathology
  • Trauma Severity Indices
  • Wounds, Nonpenetrating / immunology*
  • Wounds, Nonpenetrating / physiopathology
  • X-Ray Microtomography


  • AcPhe(ornithine-Pro-cyclohexylamine-Trp-Arg)
  • Peptides, Cyclic
  • Receptor, Anaphylatoxin C5a
  • Complement C5a