低频交变磁场促进骨组织再生效应的机制研究

Magnetic fields are widely distributed in the environment, which effect on various physiological processes of human significantely. Lots of studies indicated that electromagnetic field (EMF) could promote bone regeneration. However, most of them concentrated on the osteogenic differentiation induced by EMF and the effect of EMF on the bone cells. As we know, the development of a microvasculature and microcirculation is critical for the homeostasis and regeneration of living bone, without which, the tissue would simply degenerate and die. In the previous study, we found that EMF could up-regulate the expression of endothelial differentiation marker genes, and enhance the vascularization of tissues. According to this, we suppose that: the mechanism of therapeutic effect of EMF on bone fracture and bone defect includes not only osteogenesis action, but also vascularization; with the optimization of EMF parameters, the vascularization effect induced by EMF will be enhanced. Based on this, we designed the current project. We will optimize the EMF parameters to enhance the angiogenesis effect. In addition, the mechanism will be study as well. We will try to illustrate the angiogenesis effect of EMF from two aspects: the endothelial differentiation of bone marrow stem cell (BMSC); “paracrine secretion” induced by EMF, which will influence the action of vascular endothelial cell. In the end, we will employ animal model to evaluate the role of angiogenesis induced by EMF in the bone regeneration process. In all, this project will provide more theoretical guidance in clinical application of EMF.

磁场在地球表面是无处不在的，其对人体诸多生理活动产生了重要的影响。关于电磁场促进骨再生的研究很多，但主要集中在电磁场促进干细胞成骨分化、影响骨组织细胞活动等方面。众所周知，微血管系统对新生骨的存活和骨再生过程的持续进行有重要的意义。在前期实验中，我们发现：电磁场不仅促进成骨指标的表达，其对血管生成也有促进作用。据此，我们大胆猜测：电磁场促进骨折愈合、修复骨缺损的作用机制不仅包括促进成骨效应，还包括促血管化作用；并且该效应与电磁场的参数密切相关。在该项目中，我们拟通过磁场参数组合的变化探讨电磁场的促血管化作用，以最大程度地发挥电磁场的促血管生成效能；同时，通过分子细胞学水平的研究，拟从“成血管内皮细胞分化”和“影响血管内皮细胞生物活动的旁分泌作用”两个方面阐释电磁场的促血管化效应；并使用动物模型，评价电磁场促血管化作用在骨再生进程中所起的作用。以期为电磁场的临床应用提供更多的理论指导。

微血管系统对新生骨的存活和骨再生过程的持续进行有重要的意义。磁场无处不在，对人体诸多生理活动产生了重要的影响。关于电磁场促进骨再生的研究很多，但主要集中在电磁场促进干细胞成骨分化、影响骨组织细胞活动等方面。本课题研究了电磁场促进骨髓间充质干细胞向血管内皮细胞方向分化的效应，明确敏感效应参数区间和最佳参数值。探讨电磁场信号如何转化成生物信号，从分子水平阐释电磁场促骨髓间充质干细胞向血管内皮细胞方向分化的机制。明确骨髓间充质干细胞经过暴磁处理后是否可以引起体内血管内皮细胞的增殖和迁移。研究上述内皮细胞的增殖和迁移是否是通过“旁分泌”原理实现的。并且从体内体外两个方面为电磁场促血管化作用在骨再生领域中的应用提供了理论依据。