Studies on the gene expression of OSF-1 in osteoblasts derived from normal and osteoporosis patients.

OSF-1具有促进成骨细胞的分化和细胞生长以及促进神经元突起生长的活性。哺乳动物（人、牛、小鼠、大鼠）OSF-1的氨基酸序列高度保守，其功能在骨形成和神经发育中具有重要的基础作用。为探讨骨形成因子-1（OSF-1）在骨代谢中的作用，本研究检测了osf-1的表达与骨质疏松症的关系。人成骨细胞osf-1cDNA的核苷酸序列与脑组织中表达的osf-1cDNA的核苷酸序列完全一致。接着，比较来自骨质疏松症患者和健康人的成骨细胞的osf-1表达量。结果显示，在患者来源的成骨细胞中，I型胶原的表达略高，但osf-1和骨桥蛋白的表达水平与非患者样品几乎相同。构建了骨特异性启动子调控下过表达人osf-1基因的转基因小鼠。到目前为止，转基因小鼠的表型与非转基因小鼠相比正常。我们计划通过基因打靶的方法破坏osf-1基因的表达，构建一个osf-1基因表达缺陷的小鼠，并关注osf-1在发育过程中高表达的事实。其他骨特异性因子如BMP在骨发生和胚胎发生中起作用。为了研究osf-1在胚胎发生中的功能，我们分离了非洲爪蟾osf-1同源cDNA克隆。x-osf-1在尾芽期表达增强，表达部位仅限于后脑区。因此，osf-1被认为是一个特殊组织发育的调节因子，而不是像骨形成蛋白那样在功能水平上参与胚胎中轴的决定。

OSF-1 has the activities promoting the differentiation and cell growth on osteoblasts and neurite out growth on neurons. The amino acid sequences are highly conserved among mammals' (human, bovine, mouse, rat) OSF-1, so the functions are seemed to have important and fundamental rolls on the osteogenesis and the nerve development. To study the functions of OSF-1 on the metabolism of bone, the relationship between the osf-1 expression and osteoporosis was examined. The nucleotide sequence of osf-1 cDNA derived from human osteoblasts was cofirmed to identical to that expressed in brain tissues. Next, the amount of osf-1 expression was compared between osteoblasts derived from osteoporosis patients and from healthy individuals. As the results, the expression of type I collagen was somewhat high in osteoblasts derived from patients, but the osf-1 and osteopontine expression levels were almost the same with non-patients samples. Then transgenic mice which over express human osf-1 gene under the regulation of bone specific promoter was constructed. Until now the phenotype of the transgenic mice were normal comparing to the non-transgenic mice. We are planing to construct a mice which defect the osf-1 gene expression by disruption of the gene by the targeting method.We also focused on the fact that osf-1 is highly expressed during development. Other osteo specific factors such as BMPs are functioned in both osteogenesis and embryo genesis. To investigated the osf-1 function on the embryo genesis we isolated Xenopus laevis osf-1 homologue cDNA clones. The expression of x-osf-1 was increased at the tail-bud stage and the expression site was limited at the hind brain region. So osf-1 was thought to be a regulatory factor to develop a specialized tissues rather than the funcamental level such as BMPs which concerning in the determination of the axis of the embryo.