中文版 | English
题名

流体剪切力激活血管内皮细胞分泌信号促进成骨细胞分化

其他题名
VASCULAR ENDOTHELIAL CELLS STIMULATED BY SHEAR STRESS PROMOTE OSTEOGENISIS THROUGH SECRETED FACTORS
姓名
姓名拼音
CAI Haotian
学号
12032747
学位类型
硕士
学位专业
0710 生物学
学科门类/专业学位类别
07 理学
导师
CHAO LIU
导师单位
生物医学工程系
论文答辩日期
2023-11-08
论文提交日期
2023-12-20
学位授予单位
南方科技大学
学位授予地点
深圳
摘要

骨骼损伤严重影响人类的日常生活。骨骼再生是一个复杂的过程,血管生成在骨骼再生中扮演先决条件的角色,并为成骨微环境提供关键信号。然而,目前对于血管生成和骨形成、重塑的分子机制尚不清楚,内皮细胞与成骨细胞之间的协同作用也需要进一步研究。文献报道内皮细胞受到血液流体的剪切应力,可分泌大量的鞘氨醇-1-磷酸(S1P)。S1P 是一种生物活性溶血鞘脂,对血管生成和骨生成有着起重要作用。本研究采用流体剪切应力施加系统模拟内皮细胞受到的流体剪切力,探索 S1P 在内皮细胞与前成骨细胞之间的作用和相关机制。实验结果表明,流体剪切力刺激能促进共培养的 C166 血管内皮细胞和前成骨细胞的 YAP 核定位,并增加肌动蛋白和黏着斑蛋白的表达。C166 血管内皮细胞对力学刺激高度敏感,流体剪切力刺激促进 C166 血管内皮细胞分泌 S1P。剪切力刺激后的血管内皮细胞的条件培养液促进MC3T3-E1 前成骨细胞成骨分化、YAP 核定位以及黏着斑蛋白和β-catenin 的表达。在抑制受体 S1PR1 后,剪切力条件培养液促进 MC3T3-E1 细胞的成骨分化效果显著降低,证明流体剪切力刺激血管内皮细胞可能通过分泌 S1P 信号促进前成骨细胞的成骨分化。该研究揭示了成骨-成血管偶联过程中力学刺激血管内皮细胞与成骨分化之间的新联系。

 

其他摘要

Bone injury seriously affects daily life. Bone regeneration is a complex process. Among them, blood vessels are prerequisite for bone formation, and as a source of key signals of bone homeostasis in the bone micro-environment. However, the molecular mechanism of bone formation, remodeling, and angiogenesis are still not fully understood, and the coupling between bone cells and endothelial cells needs to be further elucidated. Sphingosine-1-phosphate (S1P) is a signaling sphingolipid, which plays an important role in angiogenesis and bone regeneration. In addition, endothelial cells are constantly being stimulated by fluid shear stress. This shear stress is also the basic decisive factor of the steady state in blood vessels. Based on the above background, we have set up an in vitro fluid shear stress stimulation system in this study to simulate vascular endothelial cells with fluid shear stress, aiming to uncover the connection between fluid shear, endothelial cells and osteoblasts. We found that the two- hour fluid shear force stimulation through in vitro cell experiments can promote YAP translocation to nucleus in co-cultured endothelial cells and osteoblasts, as well as increased expression of F-actin and vinculin. This study found that C166 vascular endothelial cells are very sensitive to mechanical stimulation. The stimulation of fluid shear promotes the secretion of S1P in C166 vascular endothelial cells. The culture medium from shear stressed C166 cells (Shear stress conditioned medium) can promote osteoblast differentiation, YAP nuclear translocation, and the expression of vinculin, β-catenin in MC3T3-E1 cells. Osteogenic differentiation is significantly reduced when S1P receptors were inhibited by W146. It was demonstrated that fluid shear stimulates vascular endothelial cells to promote osteoblast differentiation through S1P-YAP signals; and we found a new connection between shear stress stimulating vessel endothelial cells and osteogenesis in the process of osteogenesis-angiogenesis coupling.

 

关键词
其他关键词
语种
中文
培养类别
独立培养
入学年份
2020
学位授予年份
2023-12
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蔡浩添. 流体剪切力激活血管内皮细胞分泌信号促进成骨细胞分化[D]. 深圳. 南方科技大学,2023.
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