Molecular Bases for Bone Regeneration Research

骨再生研究的分子基础

基本信息

批准号：
14207056
负责人：
NODA Masaki
金额：
$ 27.62万
依托单位：
Tokyo Medical and 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：
2002
资助国家：
日本
起止时间：
2002 至 2005
项目状态：
已结题

项目摘要

This research program has been aimed to understand the mechanisms for the bone formation and bone resumption to be contributing to contemplate measures for the regeneration of bone to treat the patients suffering from osteoporosis or the large bone defects. For this program we have main three purposes. The first one is to understand the mechanisms of osteoblastic differentiation. The second project purpose is to analyze the molecular cascade for differentiation of osteoclasts. The third research aim is to elucidate mechanisms underlying the cartilage destruction and bone destruction. The first purpose, we have revealed that CIZ is acting as antagonist against BMP actions. Furthermore, osteoblastic activity as well as osteoclastic activities are under the control of sympathetic nerves tone. These molecular regulations also lead to suppression of osteoblastic transcription factors such as Runx2. In addition, other molecules such as BMP antagonist, Sost as well as HLH proteins, have been shown to work together to modulate the function of osteoblasts.For the second purpose, we analyze the molecules which are contributing to osteoclast differentiation and have shown that osteopontin as well as Klotho proteins are involved in the regulation of osteoclastic activities, Klotho protein interacts with osteoprotegrins. Bone resorption results in osteopenia. However, at the same time suppression of bone formation by Tob which also is contributing to such reduction of bone mass during the differentiation of osteoblasts. MIT-F was identified to be involved in the regulation of osteoclastic differentiation.For the third purpose, we have shown that degradation of cartilage layers in the rehumatoidarthritis models could be mediated by OPN. We have also analyze the function of transcription factor, Sox9 and identified stem cells in tendons. These three research activities altogether contributed to understanding of bone and cartilage development and regeneration.

该研究计划的目的是了解骨形成和骨骼恢复的机制，以促进骨骼再生的措施，以治疗患有骨质疏松症或大骨缺损的患者。对于此程序，我们有三个主要目的。第一个是了解成骨细胞分化的机制。第二个项目的目的是分析分子级联的破骨细胞。第三个研究目的是阐明软骨破坏和骨骼破坏的基础机制。第一个目的，我们透露，CIZ是反对BMP行动的对手。此外，成骨细胞活性以及整骨活性在交感神经音调的控制之下。这些分子法规还导致抑制成骨细胞转录因子，例如Runx2。此外，已证明其他分子（例如BMP拮抗剂，SOST和HLH蛋白）可以共同调节成骨细胞的功能。对于第二个目的，我们分析了有助于骨细胞差异的分子，并已表明与klotho蛋白相互作用的骨质蛋白与Klotho proteins相互作用。与骨蛋白。骨吸收导致骨质减少。然而，与此同时，TOB抑制骨形成，这也导致成骨细胞分化过程中骨骼质量的减少。 MIT-F被确定与整骨分化的调节有关。对于第三目的，我们已经表明，RehumatoidRhaththritis模型中软骨层的降解可以由OPN介导。我们还分析了转录因子，SOX9的功能，并在肌腱中鉴定出了干细胞。这三项研究活动完全有助于理解骨骼和软骨发育和再生。