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

本研究的目的是探索骨血管轴的基础上，在体内/离体测量骨性能和血管钙化，并评估维生素K2的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体内μCT，并确定了高转换慢性肾病（CKD）小鼠模型胫骨中小梁结构变化的时间过程。实验结束时，采用μCT和傅里叶变换红外光谱分析评价椎体皮质骨的结构和材料特性，采用von Kossa染色和等离子体原子发射光谱法检测主动脉钙化情况。CKD小鼠胫骨骨小梁网的年龄相关性退化程度高于对照小鼠。CKD组和对照组小鼠椎体皮质骨的材料特性无显著差异，两组均未出现主动脉钙化。然而，主动脉积聚的P和Ca含量在CKD中较高，并且与皮质骨厚度呈负相关，表明存在骨血管轴。另一方面，维生素K2补充剂对生长中的大鼠胫骨中的骨小梁质量和结构以及皮质骨组织的成熟具有有益的影响，显示出其在生长突增期间提高骨质量和降低骨折风险的潜力。

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.