Research on the Molecular Mechanism of Osteoporosis

这项研究确立了在骨代谢中发挥作用的分子机制，特别强调成骨细胞和破骨细胞分化的分子细节及其功能的调节。我们发现成骨细胞表达螺旋-环-螺旋(HLH型)转录因子，其表达受维生素D和骨形态发生蛋白(BMP)的调控。我们还发现，成骨细胞特异性蛋白骨钙素通过启动子区域的E-box区域在HLH-TF的控制下表达。此外，我们还发现其他类型的HLF-TF，如ADD1和HES1也在成骨细胞中表达，并分别受维甲酸和维生素D的调节。本研究主要针对在核盘体中表达的骨骼细胞相关的hlh-tf、skeraxis进行研究。我们发现硬化轴在成骨细胞中表达，并受转化生长因子β的调节。此外，TGFβ还作为成骨细胞的硬化轴进行调节。本项目还通过建立有效支持破骨细胞形成的克隆细胞系，对破骨细胞的形成进行了研究。这些在骨代谢分子和细胞细节方面的研究成果为骨质疏松症的发病机制提供了新的信号，为骨质疏松症的治疗提供了新的思路。

This research established molecular mechanisms playing a role in bone metabolism with special emphasis on the molecular detail of osteoblastic and osteoclastic differentiation as well as regulation of its function. We identified that TGFbeta-type III receptor expression is regulated by calcitropic hormones and found that osteoblastic cells express helix-loop-helix (HLH) type transcription (TF) factors whose expression is under the control of vitamin D and bone morphogenetic protein (BMP). We also found that a osteoblast-specific protein, osteocalcin, is expressed under the control of HLH-TF via the E-box region in the promoter region. Furthermore, we found that other types of HLF-TF such as ADD1 and HES1 are also expressed in osteoblasts and are regulated by retinoic acid and vitamin D respectively. This research focused especially on skeletal cell related HLH-TF,scleraxis, which is expressed in sclerotome. We found that scleraxis is expressed in osteoblasts and is regulated by TGFbeta. Furthermore, TGFbeta regulated as scleraxis in osteoblasts. Research on osteoclastogenesis was also established in this project by establishing clonal cell line which efficiently supports osteoclast formation. These accomplishments on molecular and cellular detail in bone metabolism brought new sinsignts into osteoporosis pathogenesis and contribute to establish treatment for osteoporosis.