荧光团激活蛋白分子探针用于骨代谢RANKL/RANK/OPG通路标记及作用机制研究

批准号:
82003758
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
韩小婉
依托单位:
学科分类:
老年病药物药理
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
韩小婉
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中文摘要
骨质疏松症是一种全身性骨代谢疾病,其病因非常复杂,骨重建失衡是其中的一个关键因素。受体激活核因子κB配体/受体激活核因子κB/骨保护因子(RANKL/RANK/OPG)通路在骨重建及骨代谢过程中具有重要作用,是治疗骨质疏松症的重要靶点。但目前尚无针对该靶点的小分子药物,且该信号通路的研究仍有待深入。荧光团激活蛋白(FAP, Fluorogen activating proteins)成像系统具有荧光强度高、背景干扰小、免清洗等优势,可用于信号通路的标记。本课题拟以成骨-破骨细胞体系中具有重要介导作用的RANKL为媒介,采用FAP标记RANKL的荧光成像技术,研究先导化合物E48406在成骨细胞-破骨细胞共培养体系中的作用机制,实现成骨破骨细胞相互作用的实时、可视化追踪,为阐明化合物的作用机制研究提供了有利平台,为开发新型抗骨质疏松药物提供了新的筛选平台。
英文摘要
Osteoporosis is a systemic bone metabolic disease, the cause of which is complex, and bone remodeling imbalance is one of the key factors. The receptor activated nuclear factor κB ligand/ receptor activated nuclear factor κB/ Osteoprotegerin (RANKL/RANK/OPG) pathway plays a vital role in bone remodeling and metabolism, which has been an important target for osteoporosis treatment. However, there is still no small-molecule drugs targeted on RANKL/RANK/OPG, and the pathway still needs in-depth study. Fluorogen activating proteins (FAP) imaging system has the advantages of high fluorescence intensity, low background interference, no-washing and can be used to label signal pathways. This subject intends to label RANKL, which has an important mediating role in the osteoblast-osteoclast system, using FAP fluorescence imaging technology to study the mechanism of lead compound E48406 in the osteoblast-osteoclast co-culture system. This subject will achieve real-time, visual tracking of the interaction of osteoblasts and osteoclasts and provide an advantageous platform for elucidating the mechanism of the compound and a new screening platform for the developing novel anti-osteoporosis drugs.
期刊论文列表
专著列表
科研奖励列表
会议论文列表
专利列表
DOI:10.1021/acs.analchem.3c00827
发表时间:2023-05-01
期刊:ANALYTICAL CHEMISTRY
影响因子:7.4
作者:Han,Xiaowan;Meng,Xiangchuan;Hu,Hai-Yu
通讯作者:Hu,Hai-Yu
DOI:10.1016/j.bioorg.2021.105361
发表时间:2021-09
期刊:Bioorganic chemistry
影响因子:5.1
作者:Chao Liu;Yining Li;Ren Sheng;Xiaowan Han;Li Bao;Chenyin Wang;Weizhi Wang;Xinhai Jiang;Jiangxue Han;Lijuan Lei;Ni Li;Jing Zhang;Minghua Chen;Yan Li;Ye-xiang Wu;Shunwang Li;Y. Ren;Yanni Xu;S. Si
通讯作者:Chao Liu;Yining Li;Ren Sheng;Xiaowan Han;Li Bao;Chenyin Wang;Weizhi Wang;Xinhai Jiang;Jiangxue Han;Lijuan Lei;Ni Li;Jing Zhang;Minghua Chen;Yan Li;Ye-xiang Wu;Shunwang Li;Y. Ren;Yanni Xu;S. Si
Developing fluoromodule-based probes for in vivo monitoring the bacterial infections and antibiotic responses
开发基于氟模块的探针用于体内监测细菌感染和抗生素反应
DOI:10.1016/j.talanta.2021.122610
发表时间:2021-06-18
期刊:TALANTA
影响因子:6.1
作者:Wang,Xiang;Wang,Qinghua;Hu,Hai-Yu
通讯作者:Hu,Hai-Yu
国内基金
海外基金
