Osteal macrophages promote in vivo intramembranous bone healing in a mouse tibial injury model

Authors

  • Kylie A Alexander,

    1. The University of Queensland, UQ Centre for Clinical Research, Herston, Australia
    2. The University of Queensland, Institute for Molecular Bioscience, St Lucia, Australia
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  • Ming K Chang,

    1. Institute for Biomechanics, ETH Zurich, Zürich, Switzerland
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  • Erin R Maylin,

    1. The University of Queensland, UQ Centre for Clinical Research, Herston, Australia
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  • Thomas Kohler,

    1. b-cube AG, Schlieren-Zürich, Switzerland
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  • Ralph Müller,

    1. Institute for Biomechanics, ETH Zurich, Zürich, Switzerland
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  • Andy C Wu,

    1. Griffith University School of Medical Science, Southport, Australia
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  • Nico Van Rooijen,

    1. Department of Molecular Cell Biology, Vrije Universiteit, Amsterdam, The Netherlands
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  • Matthew J Sweet,

    1. The University of Queensland, Institute for Molecular Bioscience, St Lucia, Australia
    2. The University of Queensland, Australian Infectious Diseases Research Centre, Queensland, Australia
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  • David A Hume,

    1. The University of Queensland, Institute for Molecular Bioscience, St Lucia, Australia
    2. Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin, Midlothian, Scotland, UK
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  • Liza J Raggatt,

    Corresponding author
    1. The University of Queensland, UQ Centre for Clinical Research, Herston, Australia
    2. The University of Queensland, Institute for Molecular Bioscience, St Lucia, Australia
    • The University of Queensland, UQ Centre for Clinical Research, Building 71/918, Royal Brisbane and Women's Hospital, Herston, Queensland, 4029, Australia.
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  • Allison R Pettit

    Corresponding author
    1. The University of Queensland, UQ Centre for Clinical Research, Herston, Australia
    2. The University of Queensland, Institute for Molecular Bioscience, St Lucia, Australia
    • The University of Queensland, UQ Centre for Clinical Research, Building 71/918, Royal Brisbane and Women's Hospital, Herston, Queensland, 4029, Australia.
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Abstract

Bone-lining tissues contain a population of resident macrophages termed osteomacs that interact with osteoblasts in vivo and control mineralization in vitro. The role of osteomacs in bone repair was investigated using a mouse tibial bone injury model that heals primarily through intramembranous ossification and progresses through all major phases of stabilized fracture repair. Immunohistochemical studies revealed that at least two macrophage populations, F4/80+Mac-2−/lowTRACP osteomacs and F4/80+Mac-2hiTRACP inflammatory macrophages, were present within the bone injury site and persisted throughout the healing time course. In vivo depletion of osteomacs/macrophages (either using the Mafia transgenic mouse model or clodronate liposome delivery) or osteoclasts (recombinant osteoprotegerin treatment) established that osteomacs were required for deposition of collagen type 1+ (CT1+) matrix and bone mineralization in the tibial injury model, as assessed by quantitative immunohistology and micro–computed tomography. Conversely, administration of the macrophage growth factor colony-stimulating factor 1 (CSF-1) increased the number of osteomacs/macrophages at the injury site significantly with a concurrent increase in new CT1+ matrix deposition and enhanced mineralization. This study establishes osteomacs as participants in intramembranous bone healing and as targets for primary anabolic bone therapies. © 2011 American Society for Bone and Mineral Research.

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