Grigoriadis A E, Wang Z Q, Cecchini M G, Hofstetter W, Felix R, Fleisch H A, Wagner E F
Research Institute of Molecular Pathology (IMP), Vienna, Austria.
Science. 1994 Oct 21;266(5184):443-8. doi: 10.1126/science.7939685.
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.
缺乏原癌基因c-fos的小鼠会患上骨硬化症这种骨骼疾病。研究发现，Fos突变小鼠在破骨细胞（负责吸收骨骼的细胞）的分化过程中存在障碍，且这种障碍存在于造血细胞内部。骨髓移植挽救了骨硬化症，而异位c-fos表达克服了这种分化障碍。Fos的缺失还导致破骨细胞和巨噬细胞之间的谱系转变，从而使骨髓巨噬细胞数量增加。这些结果表明，Fos是体内破骨细胞-巨噬细胞谱系决定的关键调节因子，并为代谢性骨病的分子机制提供了见解。
