OGT-AMPK通路调控成骨分化成熟的机制研究

批准号:
82000836
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
杜宇
依托单位:
学科分类:
骨转换、骨代谢异常及钙磷代谢异常
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
杜宇
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中文摘要
OGT(O-GlcNAc转移酶)与AMPK(AMP活化蛋白激酶)是与能量代谢密切相关的关键酶,参与许多疾病的发生发展,其各自在骨质疏松领域的调控作用均有报道,但OGT促进成骨分化成熟的意义及机制尚不明确。本项目前期研究发现OGT在骨质疏松模型内异常表达;在激活或抑制OGT后分别对成骨细胞的成骨分化成熟产生了正向或负向调控;OGT可以相互作用并糖基化修饰AMPK,且促进AMPK的激酶活性。本项目将进一步在临床、动物水平检测OGT与骨质疏松的相关性,通过糖基化质谱、构建突变体、体外糖基化反应、回转突变体等方法来研究OGT糖基化AMPK的具体机制及OGT依赖对AMPK的糖基化参与成骨调控,最后通过构建OGT条件性基因敲除小鼠模型来确认OGT在骨质疏松发生的意义。本研究有助于明确OGT对骨质疏松发生的意义,阐明OGT-AMPK通路调控成骨分化的具体机制,为骨质疏松提供新的理论依据和治疗靶点。
英文摘要
OGT (O-GlcNAc transferase) and AMPK (AMP-activated protein kinase) are key enzymes closely related to energy metabolism and involved in the occurrence and development of many diseases. Their respective transformation effects in the field of osteoporosis have been reported, but the significance and mechanism of OGT to promote osteogenic differentiation and maturity are not clear. Earlier research in this project found that OGT was abnormally expressed in the osteoporosis model; after activating or inhibiting OGT, they produced positive or negative osteoblast differentiation and maturation; OGT can interact and O-GlcNAc glycosylate AMPK to promote the activation of AMPK..In this study, The correlation between OGT and osteoporosis will be detected at the Clinical and animal level. The specific mechanism of glycosylated AMPK in OGT will be identified by glycosylation mass spectrometry, recombinant mutants, and in vitro glycosylation modification reactions.To find out whether OGT's osteogenesis regulation mechanism depends on the glycosylation of AMPK, by overexpression of AMPK glycosylation site mutant or wildtype in the AMPK knockdown osteoblast cell line andthen activating OGT to see if it can repeat OGT's positive regulation of osteogenesis differentiation. A conditional knockout mouse model will be constucted to confirm the significance of OGT in osteoporosis. .This study may clarify the significance of OGT on the occurrence of osteoporosis, the specific mechanism of OGT-AMPK pathway to regulate osteogenic differentiation, and provide a new theoretical basis and therapeutic target for osteoporosis.
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DOI:10.1155/2023/5915988
发表时间:2023
期刊:Stem cells international
影响因子:4.3
作者:He WG;Deng YX;Ke KX;Cao XL;Liu SY;Yang YY;Luo HH;Yao XT;Gao X;Du Y;He BC;Chen L
通讯作者:Chen L
OGT介导的糖基化修饰在BMP9诱导间充质干细胞成骨分化中的作用及机制研究
- 批准号:n/a
- 项目类别:省市级项目
- 资助金额:0.0万元
- 批准年份:2022
- 负责人:杜宇
- 依托单位:
国内基金
海外基金
