Molecular Analyses of Osteoblastic Niche and its Application with the Development of Nano Science

纳米科学发展下成骨细胞微环境的分子分析及其应用

基本信息

批准号：
18109011
负责人：
NODA Masaki
金额：
$ 70.05万
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 (S)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2010
项目状态：
已结题

项目摘要

To understand the mechanism of boneformation factors that are involved in the regulation and pathology, we have been examining molecular bases with respect to the micro environment. We identified that and CIZ is involved in the regulations ob bone information by altering the signaling of osteoblasts. CIZ and ECM proteins are regulating cell attachment and transcription. BMP is a most critical cytokine for bone information and implicated in niche regulation. Niche for bone cells and the regulation of cells in such location has not been well elucidated. As interaction of local and systemic hormone is important for coordinate regulation of bone formation we focused on parathyroid hormone (PTH). Such systemic hormonal control exerts its effect through the regulation of local target tissues, which in turn regulate upstream signals in a feedback loop. Parathyroid hormone receptor (PPR) transgenic mice expressing a constitutively active form of the receptor (caPPR) specifically in cells of th … More e osteoblast lineage have a high bone mass phenotype. In these mice, OPN deficiency further increased bone mass. Bone formation was also found to be controlled by ANA and Cnot7 that inhibit BMP. Epigentic link and PTH dependent regulation by M-CSF and MCP is also found to be important. Regeneration of bone requires the combination of appropriate drugs and an appropriate delivery system to control cell behavior. However, the delivery of multiple drugs to heal bone is complicated by the availability of carriers. The aim of this study was to explore a new system for delivery of a selective EP4 receptor agonist (EP4A) in combination with low-dose bone morphogenetic protein 2 (BMP-2). Combination treatment with EP4A and low-dose BMP-2 in nanogel efficiently activated bone cells to regenerate calvarial bone by forming both outer and inner cortical plates as well as bone marrow tissue to regenerate a structure similar to that of intact calvaria. EP4A enhanced low-dose BMP-2-induced cell differentiation and activation of transcription events in osteoblasts. These data indicate that combined delivery of EP4A and low-dose BMP-2 via nanogel-based hydrogel provides a new system for bone repair. Less

为了了解调节和病理中涉及的骨形成因子的机制，我们一直在研究相对于微环境的分子碱基。我们发现，CIZ通过改变成骨细胞的信号来参与调节OB骨信息。 CIZ和ECM蛋白是调节细胞的附着和转录。 BMP是用于骨信息的最关键的细胞因子，并在利基调节中实施。骨细胞的细分市场和在这种位置的细胞调节尚未得到很好的阐明。由于局部和全身马酮的相互作用对于坐标骨形成很重要，因此我们着重于甲状旁腺激素（PTH）。这种系统性的horsemonal控制通过调节本地目标时间来执行其效果，进而调节反馈回路中的上游信号。甲状旁腺马酮受体（PPR）转基因小鼠，表达受体的组成型活性形式（CAPPR），特别是在Th的细胞中……更多的成骨细胞谱系具有较高的骨质量表型。在这些小鼠中，OPN缺乏症进一步增加了骨骼质量。还发现骨形成受抑制BMP的ANA和CNOT7的控制。还发现了M-CSF和MCP的表观遗传联系和PTH依赖性调节很重要。骨骼的再生需要合适的药物和适当的递送系统来控制细胞行为。但是，多种药物的治愈骨骼的递送使载体的可用性变得复杂。这项研究的目的是探索一种新的系统，用于与低剂量骨形态发生蛋白2（BMP-2）结合使用选择性EP4受体激动剂（EP4A）。纳米凝胶中用EP4A和低剂量BMP-2的组合处理有效激活骨细胞，通过形成外皮层和内部皮质板以及骨髓组织来再生钙质细胞，从而再生与完整钙的结构相似的结构。 EP4A增强了低剂量BMP-2诱导的细胞分化和成骨细胞中转录事件的激活。这些数据表明，通过基于纳米凝胶的水凝胶，EP4A和低剂量BMP-2的结合递送提供了一种用于骨修复的新系统。较少的