核结合因子a1的调控机制

Cbfa1是骨发育过程中调节骨髓基质干细胞向成骨细胞分化和成熟的重要转录因子。Cbfa1的表达水平异常与骨骼系统疾病有关。体内体外实验证实多种通路(如Wnt/LRP5/-catenin,BMP/Smads,1,25-(OH)2-vitaminD3/VDR/VDRE途径)和调节蛋白(Msx2,Dlx5,Twists)在Cbfa1基因表达、活性和随后的骨形成过程中起关键作用。这些发现对调控成骨细胞分化和治疗骨质疏松以及其他伴有骨量改变的疾病治疗提供了新的思路,这些疾病有可能用控制Cbfa1表达来进行治疗。     

骨肉瘤中cbfa1基因表达与临床因素的相关性研究

目的 ｃｂｆａｌ基因是一种结合在Ｏｓｔｅｏｃａｌｃｉｎ启动子上并能调节其在成骨细胞中表达的转录因子,在成骨细胞的分化和成熟中起着重要的作用。由于ｃｂｆａｌ基因在成骨分化过程中所起的重要作用。研究骨肉瘤中ｃｂｆａｌ的表达有重要的意义。方法 应用Ｓｏｕｔｈｅｒｎ ｂｌｏｔ法ＲＴ－ＰＣＲ技术对４３例骨肉瘤标本和３株骨肉瘤细胞系（ＳＯＳ－２,ＨＯＳ和Ｕ－２）中ｃｂｆａｌ基因的结构和表达进行了研究。     

Integrin‐associated tyrosine kinase FAK affects Cbfa1 expression

Following cell adhesion, focal adhesion kinase (FAK) autophosphorylates on tyrosine and regulates intracellular signaling cascades that regulate cell growth and differentiation. The hypothesis of this study was FAK mediates osteoblast differentiation dependent Cbfa1 expression. Slowly mineralizing UI and rapidly mineralizing UMR‐106‐01 BSP osteoblasts formed focal adhesions; however, the level of FAK in UI focal adhesions was less than that seen in BSP cells. UI cultures had less FAK expression (p < 0.05) along with elevated levels of FAK phosphotyrosine in comparison to rapidly mineralizing BSP cultures. Mineralization decreased in a dose‐dependent manner in response to Herbimycin A, a tyrosine kinase inhibitor. Overexpression of FAK in UI cells led to a fourfold increase in Cbfa1 gene expression (p < 0.02), and an increase in Cbfa1 protein expression. These results suggest that the integrin‐associated tyrosine kinase FAK contributes to the regulation of the osteoblast differentiation in part through the regulation of Cbfa1 expression. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29: 1443–1447, 2011