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Inhibitory effect of vitamin K2 on vascular calcification and osteoporosis : experimental approach to understanding the bone-vascular axis

维生素 K2 对血管钙化和骨质疏松的抑制作用：了解骨血管轴的实验方法

基本信息

批准号：
21650112
负责人：
MATSUMOTO Takeshi
金额：
$ 2.21万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Challenging Exploratory Research
财政年份：
2009
资助国家：
日本
起止时间：
2009 至 2011
项目状态：
已结题

项目摘要

This study aims to explore the bone-vascular axis based on in vivo/ ex vivo measurements of bone properties and vascular calcification and to evaluate the inhibitory effects of vitamin K2 intake on these metabolic disorders. We established in vivoμCT, which was customized for imaging of mouse hindlimbs, and determined the time course of trabecular architectural changes in the tibia of a mouse model of high-turnover chronic kidney disease(CKD). At the end of the experimental period, structural and material properties of vertebral cortical bone were evaluated byμCT and Fourier transform infrared microspectroscopy, and aortic calcification was examined by von Kossa staining and plasma atomic emission spectrometry. The age-related regression of tibial trabecular network was observed to the higher degree in CKD mice than in control mice. The material properties of vertebral cortical bone did not differ significantly between CKD and control mice, and there was no appearance of aortic calcification in both groups. However, aortic accumulation of P and Ca contents were higher in CKD and inversely correlated with the cortical bone thickness, suggesting the existence of a bone-vascular axis. On the other hand, vitamin K2 supplementation had a beneficial effect on trabecular bone mass and architecture as well as the maturation of cortical bone tissue in growing rat tibiae, showing its potential to enhance bone quality and reducing fracture risk during growth spurts.

本研究旨在通过对骨骼特性和血管钙化的体内外测量，探索骨-血管轴，并评价维生素K2摄入对这些代谢紊乱的抑制作用。我们建立了用于小鼠后肢成像的在体μCT，并测定了高周转率慢性肾脏病小鼠模型胫骨小梁结构变化的时程。实验结束后，用μCT和傅里叶变换红外光谱仪评价椎体皮质骨的结构和材料特性，用von Kossa染色和等离子体原子发射光谱检测主动脉钙化。CKD组小鼠胫骨小梁网络与年龄相关的退行性变程度高于对照组。CKD组小鼠椎体皮质骨材料性能与对照组无明显差异，两组小鼠均未见主动脉钙化。然而，CKD患者的主动脉P和Ca含量较高，且与皮质骨厚度呈负相关，提示存在骨-血管轴。另一方面，补充维生素K2对生长期大鼠胫骨的骨小梁质量和结构以及皮质骨组织的成熟都有有利的影响，显示出其在生长突发期提高骨质量和降低骨折风险的潜力。