Jochum W, David J P, Elliott C, Wutz A, Plenk H, Matsuo K, Wagner E F
Research Institute of Molecular Pathology (I.M.P.), Dr. Bohr-Gasse 7, A-1030 Vienna, Austria.
Nat Med. 2000 Sep;6(9):980-4. doi: 10.1038/79676.
Bone formation by osteoblasts is essential for skeletal growth and remodeling. Fra-1 is a c-Fos-related protein belonging to the AP-1 family of transcription factors. Here we show that transgenic mice overexpressing Fra-1 in various organs develop a progressive increase in bone mass leading to osteosclerosis of the entire skeleton, which is due to a cell-autonomous increase in the number of mature osteoblasts. Moreover, osteoblast differentiation, but not proliferation, was enhanced and osteoclastogenesis was also elevated in vitro. These data indicate that, unlike c-Fos, which causes osteosarcomas, Fra-1 specifically enhances bone formation, which may be exploited to stimulate bone formation in pathological conditions.
成骨细胞形成骨对于骨骼生长和重塑至关重要。Fra-1是一种与c-Fos相关的蛋白质，属于转录因子AP-1家族。在此我们表明，在各种器官中过表达Fra-1的转基因小鼠骨量逐渐增加，导致整个骨骼发生骨硬化，这是由于成熟成骨细胞数量的细胞自主性增加所致。此外，体外成骨细胞分化（而非增殖）增强，破骨细胞生成也增加。这些数据表明，与导致骨肉瘤的c-Fos不同，Fra-1特异性增强骨形成，这可用于在病理状况下刺激骨形成。
