C-FOS - A KEY REGULATOR OF OSTEOCLAST-MACROPHAGE LINEAGE DETERMINATION AND BONE REMODELING

Mice lacking the proto-oncogene c-fos develop the bone disease osteope trosis. Fos mutant mice were found to have a block in the differentiat ion of bone-resorbing osteoclasts that was intrinsic to hematopoietic cells. Bone marrow transplantation rescued the osteopetrosis, and ecto pic c-fos expression overcame this differentiation block. The lack of Fos also caused a lineage shift between osteoclasts and macrophages th at resulted in increased numbers of bone marrow macrophages. These res ults identify Fos as a key regulator of osteoclast-macrophage lineage determination in vivo and provide insights into the molecular mechanis ms underlying metabolic bone diseases.