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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.

本研究计划旨在了解骨形成和骨恢复的机制，以有助于考虑骨再生的措施，以治疗患有骨质疏松症或大骨缺损的患者。对于这个项目，我们有三个主要目的。首先是了解成骨细胞分化的机制。第二个项目目的是分析破骨细胞分化的分子级联反应。第三个研究目标是阐明软骨破坏和骨破坏的机制。第一个目的，我们已经揭示了CIZ是作为拮抗剂对BMP的行动。此外，成骨细胞的活动以及骨代谢活动是在交感神经张力的控制下。这些分子调控也导致成骨细胞转录因子如Runx 2的抑制。此外，BMP拮抗剂、Sost蛋白和HLH蛋白等也参与了成骨细胞的功能调节。第二，我们分析了促进破骨细胞分化的分子，发现骨桥蛋白和Klotho蛋白都参与了成骨细胞活性的调节，Klotho蛋白与骨保护素相互作用。骨吸收导致骨质减少。然而，同时Tob抑制骨形成，这也有助于成骨细胞分化期间骨量的减少。MIT-F参与了骨细胞分化的调控，而OPN则参与了类风湿性关节炎模型中软骨层的降解。我们还分析了转录因子Sox 9的功能，并鉴定了肌腱中的干细胞。这三项研究活动共同促进了对骨和软骨发育和再生的理解。