Osteal Macrophages Promote In Vivo Intramembranous Bone Healing in a Mouse Tibial Injury Model

被引:383
作者
Alexander, Kylie A. [1 ,2 ]
Chang, Ming K. [3 ]
Maylin, Erin R. [1 ]
Kohler, Thomas [4 ]
Mueller, Ralph [3 ]
Wu, Andy C. [5 ]
Van Rooijen, Nico [6 ]
Sweet, Matthew J. [2 ,9 ]
Hume, David A. [2 ,7 ,8 ]
Raggatt, Liza J. [1 ,2 ]
Pettit, Allison R. [1 ,2 ]
机构
[1] Univ Queensland, UQ Ctr Clin Res, Herston, Qld 4029, Australia
[2] Univ Queensland, Inst Mol Biosci, St Lucia, Qld, Australia
[3] ETH, Inst Biomech, Zurich, Switzerland
[4] B Cube AG, Schlieren, Switzerland
[5] Griffith Univ, Sch Med Sci, Southport, Qld 4215, Australia
[6] Vrije Univ Amsterdam, Dept Mol Cell Biol, Amsterdam, Netherlands
[7] Univ Edinburgh, Roslin Inst, Roslin, Midlothian, Scotland
[8] Univ Edinburgh, Royal Dick Sch Vet Studies, Roslin, Midlothian, Scotland
[9] Univ Queensland, Australian Infect Dis Res Ctr, Brisbane, Qld 4072, Australia
基金
澳大利亚国家健康与医学研究理事会;
关键词
MACROPHAGE; OSTEOBLAST; OSTEOCLAST; OSTEOMAC; BONE FORMATION; COLONY-STIMULATING FACTOR; MONONUCLEAR PHAGOCYTE SYSTEM; CRUCIAL ROLE; REPAIR; PHOSPHATASE; EXPRESSION; RECEPTOR; OSTEOCLASTOGENESIS; OSTEOPROTEGERIN; IDENTIFICATION;
D O I
10.1002/jbmr.354
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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. (C) 2011 American Society for Bone and Mineral Research.
引用
收藏
页码:1517 / 1532
页数:16
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