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

本研究旨在通过在体内/离体测量骨骼特性和血管钙化来探索骨-血管轴，并评估维生素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体内μ ct，并确定了高周转率慢性肾脏疾病（CKD）小鼠模型胫骨小梁结构变化的时间过程。实验结束时，采用μ ct和傅里叶变换红外显微光谱法评价椎体皮质骨的结构和材料特性，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。与对照组相比，CKD小鼠胫骨小梁网络的年龄相关退化程度更高。在CKD小鼠和对照组小鼠之间，椎体皮质骨的材料特性没有显著差异，两组均未出现主动脉钙化。然而，CKD患者主动脉中P和Ca含量的积累较高，且与皮质骨厚度呈负相关，表明存在骨-血管轴。另一方面，补充维生素K2对生长中的大鼠胫骨的骨小梁骨量和结构以及皮质骨组织的成熟有有益的影响，显示其在生长高峰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.