title: c-Fos: a key regulator of osteoclast-macrophage lineage determination and bone remodeling.
abstract: Mice lacking the proto-oncogene c-fos develop the bone disease osteopetrosis. Fos mutant mice were found to have a block in the differentiation of bone-resorbing osteoclasts that was intrinsic to hematopoietic cells. Bone marrow transplantation rescued the osteopetrosis, and ectopic c-fos expression overcame this differentiation block. The lack of Fos also caused a lineage shift between osteoclasts and macrophages that resulted in increased numbers of bone marrow macrophages. These results identify Fos as a key regulator of osteoclast-macrophage lineage determination in vivo and provide insights into the molecular mechanisms underlying metabolic bone diseases.
authors.affiliation: Research Institute of Molecular Pathology (IMP), Vienna, Austria.
authors.forename: A E
authors.initials: AE
authors.lastname: Grigoriadis
authors.forename: Z Q
authors.initials: ZQ
authors.lastname: Wang
authors.forename: M G
authors.initials: MG
authors.lastname: Cecchini
authors.forename: W
authors.initials: W
authors.lastname: Hofstetter
authors.forename: R
authors.initials: R
authors.lastname: Felix
authors.forename: H A
authors.initials: HA
authors.lastname: Fleisch
authors.forename: E F
authors.initials: EF
authors.lastname: Wagner
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D016723:Bone Remodeling / Q000502:physiology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D016762:Genes, fos; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D008264:Macrophages / Q000166:cytology*; D051379:Mice; D008817:Mice, Mutant Strains; D010010:Osteoclasts / Q000166:cytology*; D010012:Osteogenesis; D010022:Osteopetrosis / Q000378:metabolism / Q000473:pathology; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000502:physiology*
chemical_list: D016760:Proto-Oncogene Proteins c-fos