title: Fracture Healing Is Delayed in Immunodeficient NOD/scid‑﻿IL2Rγ﻿cnull Mice.
abstract: Following bone fracture, the repair process starts with an inflammatory reaction at the fracture site. Fracture healing is disturbed when the initial inflammation is increased or prolonged, whereby, a balanced inflammatory response is anticipated to be crucial for fracture healing, because it may induce down-stream responses leading to tissue repair. However, the impact of the immune response on fracture healing remains poorly understood. Here, we investigated bone healing in NOD/scid-IL2Rγcnull mice, which exhibit severe defects in innate and adaptive immunity, by biomechanical testing, histomorphometry and micro-computed tomography. We demonstrated that NOD/scid-IL2Rγcnull mice exhibited normal skeletal anatomy and a mild bone phenotype with a slightly reduced bone mass in the trabecular compartment in comparison to immunocompetent Balb/c mice. Fracture healing was impaired in immunodeficient NOD/scid-IL2Rγcnull mice. Callus bone content was unaffected during the early healing stage, whereas it was significantly reduced during the later healing period. Concomitantly, the amount of cartilage was significantly increased, indicating delayed endochondral ossification, most likely due to the decreased osteoclast activity observed in cells isolated from NOD/scid-IL2Rγcnull mice. Our results suggest that--under aseptic, uncomplicated conditions--the immediate immune response after fracture is non-essential for the initiation of bone formation. However, an intact immune system in general is important for successful bone healing, because endochondral ossification is delayed in immunodeficient NOD/scid-IL2Rγcnull mice.
authors: Institute of Orthopaedic Research and Biomechanics, University of Ulm, Ulm, Germany.
authors: Anna E
authors: AE
authors: Rapp
authors: Institute of Orthopaedic Research and Biomechanics, University of Ulm, Ulm, Germany.
authors: Ronny
authors: R
authors: Bindl
authors: Institute of Orthopaedic Research and Biomechanics, University of Ulm, Ulm, Germany.
authors: Stefan
authors: S
authors: Recknagel
authors: Department of General Paediatrics, Haematology and Oncology, University Children's Hospital Tübingen, Tübingen, Germany.
authors: Annika
authors: A
authors: Erbacher
authors: Clinic for Paediatric Haematology and Oncology, Bone Marrow Transplantation Unit, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
authors: Ingo
authors: I
authors: Müller
authors: Institute of Clinical Transfusion Medicine and Immunogenetics, German Red Cross Blood Transfusion Service and University Hospital Ulm, Baden Wuerttemberg-Hessen, Ulm, Germany.|Institute of Transfusion Medicine, University of Ulm, Ulm, Germany.
authors: Hubert
authors: H
authors: Schrezenmeier
authors: Department of Traumatology, Hand-, Plastic, and Reconstructive Surgery, Centre of Surgery, University of Ulm, Ulm, Germany.
authors: Christian
authors: C
authors: Ehrnthaller
authors: Department of Traumatology, Hand-, Plastic, and Reconstructive Surgery, Centre of Surgery, University of Ulm, Ulm, Germany.
authors: Florian
authors: F
authors: Gebhard
authors: Institute of Orthopaedic Research and Biomechanics, University of Ulm, Ulm, Germany.
authors: Anita
authors: A
authors: Ignatius
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D001862:Bone Resorption / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D017102:Fracture Healing / Q000235:genetics* / Q000276:immunology*; D053631:Interleukin Receptor Common gamma Subunit / Q000172:deficiency* / Q000235:genetics*; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D010006:Osteoblasts / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism; D010012:Osteogenesis / Q000235:genetics / Q000276:immunology; D010641:Phenotype; D055114:X-Ray Microtomography
chemical_list: D053631:Interleukin Receptor Common gamma Subunit