title: Macrophages: Their Emerging Roles in Bone.
abstract: Macrophages are present in nearly all tissues and are critical for development, homeostasis, and regeneration. Resident tissue macrophages of bone, termed osteal macrophages, are recently classified myeloid cells that are distinct from osteoclasts. Osteal macrophages are located immediately adjacent to osteoblasts, regulate bone formation, and play diverse roles in skeletal homeostasis. Genetic or pharmacological modulation of macrophages in vivo results in significant bone phenotypes, and these phenotypes depend on which macrophage subsets are altered. Macrophages are also key mediators of osseous wound healing and fracture repair, with distinct roles at various stages of the repair process. A central function of macrophages is their phagocytic ability. Each day, billions of cells die in the body and efferocytosis (phagocytosis of apoptotic cells) is a critical process in both clearing dead cells and recruitment of replacement progenitor cells to maintain homeostasis. Recent data suggest a role for efferocytosis in bone biology and these new mechanisms are outlined. Finally, although macrophages have an established role in primary tumors, emerging evidence suggests that macrophages in bone support cancers which preferentially metastasize to the skeleton. Collectively, this developing area of osteoimmunology raises new questions and promises to provide novel insights into pathophysiologic conditions as well as therapeutic and regenerative approaches vital for skeletal health.
authors.affiliation: Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA.
authors.forename: Benjamin P
authors.initials: BP
authors.lastname: Sinder
authors.affiliation: Blood and Bone Diseases Program, Mater Research Institute-The University of Queensland, Translational Research Institute, Woolloongabba, Australia.
authors.forename: Allison R
authors.initials: AR
authors.lastname: Pettit
authors.affiliation: Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA.|Department of Pathology, University of Michigan, Medical School, Ann Arbor, MI, USA.
authors.forename: Laurie K
authors.initials: LK
authors.lastname: McCauley
mesh_terms: D000818:Animals; D017209:Apoptosis; D001842:Bone and Bones / Q000166:cytology / Q000502:physiology*; D017102:Fracture Healing; D006706:Homeostasis; D006801:Humans; D007107:Immune System; D007150:Immunohistochemistry; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000166:cytology*; D010587:Phagocytosis; D010641:Phenotype; D014945:Wound Healing
keywords: BONE FORMATION; EFFEROCYTOSIS; FRACTURE REPAIR; MACROPHAGE; SKELETAL METASTASIS