c-Fos: a key regulator of osteoclast-macrophage lineage determination and bone remodeling.
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.
Grigoriadis
A E
AE
Research Institute of Molecular Pathology (IMP), Vienna, Austria.
Wang
Z Q
ZQ
Cecchini
M G
MG
Hofstetter
W
W
Felix
R
R
Fleisch
H A
HA
Wagner
E F
EF
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*
D016760:Proto-Oncogene Proteins c-fos