title: C5aR-antagonist significantly reduces the deleterious effect of a blunt chest trauma on fracture healing.
abstract: 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.
authors.affiliation: Institute of Orthopaedic Research and Biomechanics, Center of Musculoskeletal Research, University of Ulm, Helmholtzstr.14, 89081 Ulm, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Recknagel
authors.forename: Ronny
authors.initials: R
authors.lastname: Bindl
authors.forename: Julian
authors.initials: J
authors.lastname: Kurz
authors.forename: Tim
authors.initials: T
authors.lastname: Wehner
authors.forename: Philipp
authors.initials: P
authors.lastname: Schoengraf
authors.forename: Christian
authors.initials: C
authors.lastname: Ehrnthaller
authors.forename: Hongchang
authors.initials: H
authors.lastname: Qu
authors.forename: Florian
authors.initials: F
authors.lastname: Gebhard
authors.forename: Markus
authors.initials: M
authors.lastname: Huber-Lang
authors.forename: John D
authors.initials: JD
authors.lastname: Lambris
authors.forename: Lutz
authors.initials: L
authors.lastname: Claes
authors.forename: Anita
authors.initials: A
authors.lastname: Ignatius
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000502:physiology; D015936:Complement C5a / Q000037:antagonists & inhibitors / Q000276:immunology; D004195:Disease Models, Animal; D005264:Femoral Fractures / Q000000981:diagnostic imaging / Q000276:immunology* / Q000503:physiopathology; D017102:Fracture Healing / Q000187:drug effects* / Q000276:immunology; D007249:Inflammation / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D010027:Osteotomy; D010456:Peptides, Cyclic / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D044087:Receptor, Anaphylatoxin C5a / Q000037:antagonists & inhibitors* / Q000276:immunology; D013898:Thoracic Injuries / Q000276:immunology* / Q000503:physiopathology; D015599:Trauma Severity Indices; D014949:Wounds, Nonpenetrating / Q000276:immunology* / Q000503:physiopathology; D055114:X-Ray Microtomography
chemical_list: C438957:AcPhe(ornithine-Pro-cyclohexylamine-Trp-Arg); D010456:Peptides, Cyclic; D044087:Receptor, Anaphylatoxin C5a; D015936:Complement C5a