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温度调节。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。这项研究得出的重要发现是，骨形成的合成代谢活性取决于。两种 RANKL 结合肽之间的骨形成活性的比较引导我们得出这一结论。在本研究开始时，我们发现两种合成代谢肽之间的 RANKL 结合位点的差异可能导致 RANKL 反向信号强度的差异。由于只有当肽浓度高于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，例如澄清可以切换的 RANKL 分子之间的适当距离，有必要进行进一步的研究。最后我们感谢 Masashi Honma 博士（东京大学药学系）。医学院）用于分析 RANKL 反向信号传导的骨形成肽。