模拟微重力效应下初级纤毛变化规律及机制在骨细胞响应力学刺激中的作用研究

批准号:
11972068
项目类别:
面上项目
资助金额:
63.0 万元
负责人:
孙联文
依托单位:
学科分类:
多尺度力学生物学
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
孙联文
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中文摘要
失重性骨丢失发生机制尚不清楚。申请人前期基金研究显示微重力下骨细胞对流体剪切响应减弱,而其机制是本课题拟研究的科学问题。已有研究显示初级纤毛在肾等多种组织能感知力学刺激。微重力下初级纤毛可能发生改变而影响细胞对力学刺激的感知/转导,从而导致骨细胞力学敏感性下降。拟以骨细胞MLO-Y4为研究对象,研究模拟微重力效应(SM)下纤毛长度、方向及萌发的变化规律以及通过检测纤毛内转运、母中心粒位置及相关蛋白研究其变化机制;用药物抑制、过表达初级纤毛(包括SM下拮抗纤毛变化),检测细胞对流体剪切的响应,明确纤毛在骨细胞力学感知中的作用;通过检测纤毛多囊蛋白力学感知路径,并用RNAi进行调控,探究SM下纤毛改变影响细胞力学响应的途径/机制。这将有助于阐明微重力导致骨丢失的发生机制,为找寻到有效的对抗措施提供线索和依据。
英文摘要
The mechanism of microgravity-induced osteoporosis remains unclear. The alteration of osteocyte mechanosensitivity under simulated microgravity has been found by our group in the last program supported by NSFC. In this project, we will investigate why it happened. Primary cilia, as a mechanosensor in several tissues such as kidney, may play an important role in osteocytes’ responding to mechanical stimuli under microgravity. Bone cell line MLO-Y4 as the research object, this project is going to: determine the changes of the length, direction and germination rate of primary cilia and the response of cells to mechanical stimuli under simulated microgravity effect (SM); detect the mechanism of cilia changes under SM by detecting the intraflagellar transport, the location of the maternal centriole and the relative proteins; use drugs to inhibit and overexpress primary cilia, then detect the response of cells to fluid shear in order to confirm the role of primary cilia in the response of bone cells to mechanical stimuli; investigate the change of polycystins in primary cilia, use RNAi technology to regulate the expression of polycystins and then determine the response of cells to mechanical stimuli in order to explore the mechanism of primary cilia change affecting bone cell’s responses to mechanical stimuli under SM. This will help to clarify the mechanism of microgravity-induced bone loss and provide clues and evidence for finding effective countermeasures.
期刊论文列表
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科研奖励列表
会议论文列表
专利列表
Contribution of endoplasmic reticulum stress response to the mechanosensitivity alteration in osteocytes under simulated microgravity
模拟微重力下内质网应激反应对骨细胞机械敏感性变化的贡献
DOI:10.1016/j.actaastro.2021.11.037
发表时间:2021-12
期刊:Acta Astronautica
影响因子:3.5
作者:Liu Li-Jin;Li Shuang;Wu Xin-Tong;Yang Xiao;Sun Lian-Wen
通讯作者:Sun Lian-Wen
DOI:10.1016/j.actaastro.2021.08.031
发表时间:2021-12
期刊:Acta Astronautica
影响因子:3.5
作者:Wang Shou-Hui;Yang Xiao;Ding Dong;Wu Xin-Tong;Han Zhuang;Sun Lian-Wen;Fan Yu-Bo
通讯作者:Fan Yu-Bo
The microgravity induces the ciliary shortening and an increased ratio of anterograde/retrograde intraflagellar transport of osteocytes
微重力引起纤毛缩短和骨细胞顺行/逆行鞭毛内运输比例增加
DOI:10.1016/j.bbrc.2020.06.119
发表时间:2020-09-10
期刊:BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
影响因子:3.1
作者:Ding, Dong;Yang, Xiao;Fan, Yu-bo
通讯作者:Fan, Yu-bo
DOI:10.1364/boe.418418
发表时间:2021-04-01
期刊:BIOMEDICAL OPTICS EXPRESS
影响因子:3.4
作者:Cao,Runyu;Xiao,Wen;Sun,Lianwen
通讯作者:Sun,Lianwen
Effects of advanced glycation end products on osteocytes mechanosensitivity
晚期糖基化终末产物对骨细胞机械敏感性的影响
DOI:10.1016/j.bbrc.2021.06.074
发表时间:2021
期刊:Biochemical and Biophysical Research Communications
影响因子:3.1
作者:Yang Xiao;Liu Cong-Jin;Wang Zhen-Zhen;Ding Dong;Shi Jing-Wen;Wu Xin-Tong;Sun Lian-Wen;Fan Yu-Bo
通讯作者:Fan Yu-Bo
膜骨架spectrin在模拟微重力效应导致的骨细胞力敏感性改变中的作用
- 批准号:11472033
- 项目类别:面上项目
- 资助金额:92.0万元
- 批准年份:2014
- 负责人:孙联文
- 依托单位:
主/被运动对抗失重性骨质疏松的对比性研究
- 批准号:31170897
- 项目类别:面上项目
- 资助金额:60.0万元
- 批准年份:2011
- 负责人:孙联文
- 依托单位:
模拟微重力效应下骨细胞的力生物学研究
- 批准号:10872024
- 项目类别:面上项目
- 资助金额:42.0万元
- 批准年份:2008
- 负责人:孙联文
- 依托单位:
国内基金
海外基金
