Hatta Mitsutoki, Daitoku Hiroaki, Matsuzaki Hitomi, Deyama Yoshiaki, Yoshimura Yoshitaka, Suzuki Kuniaki, Matsumoto Akira, Fukamizu Akiyoshi
Center for Tsukuba Advanced Research Alliance, Institute of Applied Biochemistry, University of Tsukuba, Tsukuba, Ibaraki 305-8857, Japan.
Int J Mol Med. 2002 Feb;9(2):147-52.
Alkaline phosphatase (ALP) is a basic marker of osteoblast maturation and osteogenesis. However, the mechanisms of the ALP gene regulation in osteoblasts remain elusive. In this study, we examined the expression of forkhead transcription factor FKHR, a regulator of hepatic glucose metabolic and proapoptotic genes, in osteogenic cells and the effect of FKHR on transcription of the ALP gene. RT-PCR and immunoblot analyses revealed the expression of FKHR in osteogenic MC3T3-E1, SaOS2, and UMR 106 cells. Reporter assays demonstrated that the overexpression of FKHR stimulated ALP promoter activity through the forkhead response element in its promoter. These results suggest that ALP is a target gene regulated by FKHR and that FKHR contributes to osteoblast maturation and osteogenesis.
碱性磷酸酶(ALP)是成骨细胞成熟和骨生成的一个基本标志物。然而,成骨细胞中ALP基因调控的机制仍不清楚。在本研究中,我们检测了肝葡萄糖代谢和促凋亡基因的调节因子叉头转录因子FKHR在成骨细胞中的表达以及FKHR对ALP基因转录的影响。逆转录聚合酶链反应(RT-PCR)和免疫印迹分析显示FKHR在成骨MC3T3-E1、SaOS2和UMR 106细胞中表达。报告基因检测表明,FKHR的过表达通过其启动子中的叉头反应元件刺激ALP启动子活性。这些结果表明,ALP是受FKHR调控的靶基因,且FKHR有助于成骨细胞成熟和骨生成。