title: Macrophages promote osteoblastic differentiation in-vivo: implications in fracture repair and bone homeostasis.
abstract: Macrophages are activated in inflammation and during early phases of repair processes. Interestingly, they are also present in bone during development, but their function during this process is unclear. Here, we explore the function of macrophages in bone development, growth, and repair using transgenic mice to constitutively or conditionally deplete macrophages. Depletion of macrophages led to early skeletal growth retardation and progressive osteoporosis. By 3 months of age, macrophage-deficient mice displayed a 25% reduction in bone mineral density and a 70% reduction in the number of trabecular bone compared to control littermates. Despite depletion of macrophages, functional osteoclasts were still present in bones, lining trabecular bone and the endosteal surface of the cortical bone. Furthermore, ablation of macrophages led to a 60% reduction in the number of bone marrow mesenchymal progenitor cells and a decrease in the ability of these cells to differentiate to osteoblasts. When macrophages were depleted during fracture repair, bone union was impaired. Calluses from macrophage-deficient animals were smaller, and contained less bone and more fibrotic tissue deposition. Taken together, this shows that macrophages are crucial for maintaining bone homeostasis and promoting fracture repair by enhancing the differentiation of mesenchymal progenitors.
authors.affiliation: Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, Ontario, Canada.|Institute of Medical Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.|Department of Orthopaedic Surgery, Duke University, Durham, North Carolina, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Vi
authors.affiliation: Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Gurpreet S
authors.initials: GS
authors.lastname: Baht
authors.affiliation: Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Heather
authors.initials: H
authors.lastname: Whetstone
authors.affiliation: Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.|Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Adeline
authors.initials: A
authors.lastname: Ng
authors.affiliation: Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Qingxia
authors.initials: Q
authors.lastname: Wei
authors.affiliation: Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Raymond
authors.initials: R
authors.lastname: Poon
authors.affiliation: Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Sivakami
authors.initials: S
authors.lastname: Mylvaganam
authors.affiliation: Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.|Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Marc
authors.initials: M
authors.lastname: Grynpas
authors.affiliation: Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, Ontario, Canada.|Institute of Medical Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.|Department of Orthopaedic Surgery, Duke University, Durham, North Carolina, USA.|Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Alman
mesh_terms: D000818:Animals; D015519:Bone Density / Q000502:physiology; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D017102:Fracture Healing / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*
keywords: BONE DENSITY; BONE DEVELOPMENT; FRACTURE HEALING; LYSOZYME; MACROPHAGE; MACROPHAGE-FAS INDUCED APOPTOSIS; OSTEOBLAST; OSTEOCLAST