Analyses of Molecular Mechanisms Involved in Pathogenesis of 0steoporosis

0骨质疏松症发病分子机制分析

基本信息

批准号：
09307034
负责人：
NODA Masaki
金额：
$ 25.79万
依托单位：
Tokyo Medical Dental University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A).
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 2000
项目状态：
已结题

项目摘要

We established the molecular bases of regulation ofosteoblasts as well as osteoclasts. With regard to bone resorption, osteopontin knock out mice were produced (JBMR, 1998) and the following study indicated that this molecule is required for rapid bone resorption after estrogen depletion (Proceedings of the National Academy of Sciences U.S.A., 1999., 1999).Bone formation mechanism was studied using knockout mice and we identified (1) Tab as a novel inhibitor of bone formation in response to BMP (Cell, 2000) , (2) a unique Smad regulation of Cbfa gene expression (Journal of Biological Chemistry (JBC) 1998)(3) a novel mechanism of vitamin D regulation of ld, a negative regulator of helix loop helix type transcription factor (JBC,1997) , (4) a positive type helix-loop-helix transcription factor, Scleraxis and an HMG factor to be responsible for connective tissue gene regulation (JBC,1997)(JBC,2000).We also identified that klotho gene is involved in the regulation of bone resorption activity by regulating osteoprotegerin (Endocrinology, 2000 ; J of Endocrinology, 2000), and the klotho phenotype in bone could be rescued by virus mediated klotho expression (Journal of Gene Medicine, 2000)Mechanical stress is one of the most important aspects in contemplating osteoporosis treatment, however, no mechanism has been clarified. We found that osteopontin and klotho play critical roles and prerequisite for the bone loss in the unloaded mice (Journal of Experimental Medicine, 2001)(J of Endocrinology, 2001).Over all our research identified key molecular players in the bone volume maintenance and loss and these findings are important in understanding the pathogenesis of osteoporosis and to contemplate measures to treat patients suffering from this disease which is one of the major health problems in the modern society.

我们确定了骨细胞和破骨细胞的调节的分子碱基。在骨吸收方面，产生了骨桥蛋白敲除小鼠（JBMR，1998），以下研究表明，雌激素消耗后快速骨吸收需要快速骨吸收（U.S. U.S.A. National Acidemy of U.S.A. (Cell, 2000) , (2) a unique Smad regulation of Cbfa gene expression (Journal of Biological Chemistry (JBC) 1998)(3) a novel mechanism of vitamin D regulation of ld, a negative regulator of helix loop helix type transcription factor (JBC,1997) , (4) a positive type helix-loop-helix transcription factor, Scleraxis and an HMG factor to be responsible for connective tissue gene regulation (JBC,1997)(JBC,2000).We also identified that klotho gene is involved in the regulation of bone resorption activity by regulating osteoprotegerin (Endocrinology, 2000 ; J of Endocrinology, 2000), and the klotho phenotype in bone could be rescued by virus mediated klotho expression (Journal of Gene Medicine, 2000)Mechanical stress is one of the most但是，考虑骨质疏松治疗的重要方面，尚未澄清机制。我们发现，骨桥和克洛索在未载的小鼠中起着关键作用和骨质损失的先决条件（实验医学杂志，2001年）（内分泌学J杂志，2001年）。我们的所有研究都确定了我们在骨骼体积维持和损失中的关键分子参与者，并且这些发现在对现代疾病中的疾病中的病原体对骨骼的疾病进行了重要的疾病而重要，而这些发现是重要的。社会。