兰州大学机构库 >学院待认领
流体剪切力促进成骨细胞增殖机制的研究
Alternative TitleStudy of molecular mechanisms of osteoblastic cells proliferation induced by fluid shear stress
李鹏
Thesis Advisor夏亚一
2012-05-18
Degree Grantor兰州大学
Place of Conferral兰州
Degree Name博士
Keyword流体剪切力 成骨细胞 ERK5 细胞骨架重组 增殖
Abstract随着中国人口老龄化加剧,骨质疏松发病率正逐年增加,已成为举世瞩目的公共卫生事件。然而由于目前对骨骼力学感受机制的不明确,导致临床医生无法正确指导患者合理运动而促进其康复。本课题应用自制体外流体剪切力加载系统,对MC3T3-E1细胞和MG-63细胞加载不同强度与时间长度的流体剪切力,以ERK5为靶分子,研究成骨细胞应力信号传导机制和在成骨细胞增殖过程中的作用机制。发现流体剪切力可活化成骨细胞ERK5,细胞骨架重组在该过程中发挥重要作用,流体剪切力可能通过细胞骨架重组促进细胞膜粘附分子FAK磷酸化活化ERK5。阻断细胞骨架重组可显著下调ERK5磷酸化水平,但是对磷酸化的ERK5细胞核转位没有影响。细胞骨架在流体剪切力刺激下可迅速重组,然而长时间的流体力学刺激,即使是在生理强度范围内,也会导致细胞骨架破碎。循环流体剪切力可调控ERK5活化,促进AP-1和cyclin D1表达,同时抑制p-16表达促进成骨细胞增殖。与持续流体剪切力相比,循环流体剪切力更有利于促进成骨细胞增殖。MEK5阻断剂BIX02188和BIX02189均可显著抑制ERK5磷酸化,并且该阻断时间至少持续4 h。综上所述:ERK5是成骨细胞力学信号传导机制中的重要靶分子,在流体剪切力调控成骨细胞增殖过程中发挥重要作用。
Other AbstractThe incidence of osteoporosis increased along with the grievous aged population in China, and osteoporosis has become a remarkable public health issue. The mechanism of mechanotranduction of bone cells has not been fully understood, which lead to difficulties for clinicians guiding patients exercise to promote their recovery. This study use self-made fluid shear stress loading system to investigate role of ERK5 in mechanotransduction of MC3T3-E1 pre-osteoblastic cells in vitro. We found fluid shear stress activates ERK5, in which, cytoskeletal reorganization is essential, cytoskeletal reorganization dependent FAK phosphorylation induced by fluid shear stress may be involved in this mechanism. Disruption of cytoskeletal reorganization downregualtes ERK5 activation, but has no effect on ERK5 translocation. Cytoskeleton in cells could quickly reorganize into stress fibers in response to fluid shear stress, while, long time mechanical stimulation, even at physiological level, lead to cytoskeleton disruption.
URL查看原文
Language中文
Document Type学位论文
Identifierhttps://ir.lzu.edu.cn/handle/262010/223046
Collection学院待认领
Affiliation临床医学院
Recommended Citation
GB/T 7714
李鹏. 流体剪切力促进成骨细胞增殖机制的研究[D]. 兰州. 兰州大学,2012.
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