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Osteal macrophages promote in vivo intramembranous bone healing in a mouse tibial injury model
Author(s) -
Alexander Kylie A,
Chang Ming K,
Maylin Erin R,
Kohler Thomas,
Müller Ralph,
Wu Andy C,
Van Rooijen Nico,
Sweet Matthew J,
Hume David A,
Raggatt Liza J,
Pettit Allison R
Publication year - 2011
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.354
Subject(s) - intramembranous ossification , bone healing , in vivo , medicine , endochondral ossification , pathology , population , bone morphogenetic protein 2 , microbiology and biotechnology , chemistry , anatomy , biology , in vitro , cartilage , environmental health , biochemistry
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 −/low TRACP − osteomacs and F4/80 + Mac‐2 hi TRACP − 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.