SDF-1/CXCR7轴介导内皮祖细胞参与骨折修复与愈合过程的机制研究

Endothelial progenitor cells (EPCs) targeting "homing" promote vascularization,which is an important strategy to promote fracture repair and healing. This process is regulated by multiple factors, stromal derived factor-1(SDF-1) is one of the most concerns for factor, but previous studies demonstrated that SDF-1 played a role through its unique receptor CXCR4 , however, the discovery of new receptor CXCR7 need to study the novel mechanism of SDF-1 action. Our previous study confirmed that endothelial progenitor cells mobilized into the peripheral blood of patients with fracture during early stages of healing process, we propose SDF-1/CXCR7 axis mediated endothelial progenitor cells participate in the process of fracture repair and healing, In the present study, we proceed from clinical observations and animal models, through the laser doppler,Fluorescent cell sorting, ELISA, PCR and Western-blot technique to further verify the hypothesis and reveal the new mechanism of mediated endothelial progenitor cells angiogenesis, so as to further improve the understanding of endothelial progenitor cells involved in bone repair and healing, which could provide new treatment ideas support for EPCs for the clinical application of bone defects and nonunion.

内皮祖细胞（EPCs）靶向“归巢”参与新血管形成是促进骨折修复与愈合的重要机制，这一过程受多因素的调节，其中基质细胞衍生因子（SDF-1）是近年来最受关注的因子之一。以往研究已证实SDF-1是通过其唯一受体CXCR4而发挥作用的，然而，CXCR7作为SDF-1的新受体在这一过程中的作用机制尚不明确。我们前期研究证实：骨折愈合早期有大量的EPCs被动员到外周血中，因此我们提出假说：SDF-1/CXCR7轴介导内皮祖细胞参与了骨折修复与愈合的过程。本研究从临床观察和动物模型两方面着手，通过激光多普勒、流式细胞分选、ELISA、PCR及western-blot等技术，来进一步揭示SDF-1/CXCR7轴介导内皮祖细胞促血管化的可能机制，进一步完善内皮祖细胞参与骨修复和愈合过程的理论，为内皮祖细胞在骨缺损和骨不连的临床应用中提供新的治疗思路。

内皮祖细胞（EPCs）靶向“归巢”参与新血管形成是促进骨折修复与愈合的重要机制，这一过程受多因素的调节，其中基质细胞衍生因子（SDF-1）是近年来最受关注的因子之一。本课题从临床观察和动物模型两方面着手，通过免疫组化染色、流式细胞分选、ELISA、PCR及western-blot等技术，来进一步揭示SDF-1/CXCR7轴介导内皮祖细胞促血管化的可能机制，进一步完善内皮祖细胞参与骨修复和愈合过程的理论，为内皮祖细胞在骨缺损和骨不连的临床应用中提供新的治疗思路。本课题组紧跟国内外研究热点，对项目研究内容进行了适当拓展，实施完成了柚皮苷通过调节VEGF/VEGFR-2 信号刺激血管生成从而促进骨质疏松骨折愈合；柚皮苷可以增加Sema3A的表达和激活Wnt/β-catenin信号延缓废用骨质疏松；微应变应力通过MAPK-ERK1/2信号通路影响内皮祖细胞增殖；证实柚皮苷能够影响内皮祖细胞的活性，促血管化且能够促进骨质疏松骨折的愈合，这为临床上治疗骨不连以及预防骨质疏松提供参考。