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Development of a new anabolic peptide on bone by the identification

通过鉴定开发出一种新型骨合成代谢肽

基本信息

批准号：
23659867
负责人：
AOKI Kazuhiro
金额：
$ 2.33万
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 Challenging Exploratory Research
财政年份：
2011
资助国家：
日本
起止时间：
2011 至 2012
项目状态：
已结题

项目摘要

Receptor activator of NF-〓B ligand (RANKL) promotes dendritic celldifferentiation and osteoclast differentiation and function. Recent findings also revealedthe wide-ranging physiological roles of RANKL such as the mammalian gland developmentand the thermoregulation. We found in this study that RANKL binding peptides promotebone formation, leading to a significant finding to clarify the physiological roles of RANKL. This study yields the important finding that anabolic activity on bone formationwas dependent on the RANKL-reverse-signaling intensity. The comparison of boneformation activities between two RANKL-binding peptides guided us to this conclusion. Atthe beginning of this study, we hypothesized that the differences of RANKL binding sitesbetween two anabolic peptides might induce the differences of bone formation activitiesbetween the two peptides. Since the stimulatory effects of osteoblast differentiation wasappeared only when the peptide concentration was higher around100 〓M and over, wethought that making a RANKL clustering on the surface of osteoblast membrane might bea trigger of the RANKL-reverse-signaling. Further studies are necessary for leading this study toward the development of anew therapeutic agent, such as clarification of an appropriate distance between RANKLmolecules that can switch on the bone formation activity, and the development of a ligand,which can make a RANKL clustering. Finally we thank Dr. Masashi Honma (Department of Pharmacy, TheUniversity of Tokyo Hospital, Faculty of Medicine) for analyses of the bone formationpeptides on the RANKL-reverse-signaling.

NF-〓B 配体受体激活剂 (RANKL) 促进树突状细胞分化和破骨细胞分化和功能。最近的研究结果还揭示了 RANKL 的广泛生理作用，例如哺乳动物腺体发育和体温调节。我们在这项研究中发现 RANKL 结合肽促进骨形成，从而得出澄清 RANKL 生理作用的重要发现。这项研究得出了重要的发现，即骨形成的合成代谢活性依赖于 RANKL 反向信号强度。通过比较两种 RANKL 结合肽之间的骨形成活性，我们得出了这一结论。在本研究开始时，我们假设两种合成代谢肽之间的RANKL结合位点的差异可能导致两种肽之间的骨形成活性的差异。由于只有当肽浓度较高约100〓M及以上时才会出现成骨细胞分化的刺激作用，因此我们认为在成骨细胞膜表面上形成RANKL簇可能是RANKL反向信号传导的触发因素。为了引导这项研究开发新的治疗剂，需要进一步的研究，例如阐明可以开启骨形成活性的 RANKL 分子之间的适当距离，以及开发可以进行 RANKL 聚类的配体。最后，我们感谢 Masashi Honma 博士（东京大学医院药学系）对 RANKL 反向信号传导的骨形成肽进行分析。

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Gingival Overgrowth Induced by Phenytoin-Study of the Human Gingival Overgrowth Tissues and Clonal Gingival Cells-.

苯妥英诱导的牙龈过度生长-人类牙龈过度生长组织和克隆牙龈细胞的研究-。

DOI：
发表时间：
2012
期刊：
Disability and Oral Health
影响因子：
0
作者：
HAYASHI N;TAMURA Y;KUSUMOTO Y;SHIMOKAWA H;AOKI K;OHYA K;YAMAZAKI T;SHINOZUKA O
通讯作者：
SHINOZUKA O

Bone Regeneration Using Gelatin Hydrogel as a Novel Scaffold for a RANKL Antagonist Peptide W9.

使用明胶水凝胶作为 RANKL 拮抗剂肽 W9 的新型支架进行骨再生。