Nakashima Kazuhisa, de Crombrugghe Benoit
Department of Molecular Genetics, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Trends Genet. 2003 Aug;19(8):458-66. doi: 10.1016/S0168-9525(03)00176-8.
Osteoblasts, the cells responsible for bone formation, differentiate from mesenchymal cells. Here, we discuss transcription factors that are involved in regulating the multistep molecular pathway of osteoblast differentiation. Runx2 and Osx, a newly identified zinc-finger-containing protein, are transcription factors that are expressed selectively and at high levels in osteoblasts. Null mutations of either leads to a complete absence of bone in mice. Runx2 plus its companion subunit Cbf beta are needed for an early step in this pathway, whereas Osx is required for a subsequent step, namely the differentiation of preosteoblasts into fully functioning osteoblasts. The finding that Osx-null cells acquire a chondrocyte phenotype implies that Osx is a negative regulator of Sox9 and of the chondrocyte phenotype. This leads to the hypothesis that Osx might have a role in the segregation of osteoblasts from osteochondroprogenitors. We also discuss recent progress in studies of other transcription factors that affect skeletal patterning and development.
成骨细胞是负责骨形成的细胞，由间充质细胞分化而来。在此，我们讨论参与调节成骨细胞分化多步骤分子途径的转录因子。Runx2和Osx（一种新发现的含锌指蛋白）是在成骨细胞中选择性且高水平表达的转录因子。任一基因的无效突变都会导致小鼠完全无骨。Runx2及其伴侣亚基Cbf beta是该途径早期步骤所必需的，而Osx是后续步骤（即成骨前体细胞分化为功能完全的成骨细胞）所必需的。Osx基因缺失的细胞获得软骨细胞表型这一发现表明，Osx是Sox9和软骨细胞表型的负调节因子。这就引出了一个假说，即Osx可能在成骨细胞与骨软骨祖细胞的分离过程中发挥作用。我们还讨论了影响骨骼模式形成和发育的其他转录因子研究的最新进展。
