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Wnt/beta-catenin信号通路参与青少年特发性脊柱侧凸发病的机制研究
结题报告
批准号:
81972029
项目类别:
面上项目
资助金额:
55.0 万元
负责人:
朱泽章
依托单位:
学科分类:
运动系统结构、功能和发育异常
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
朱泽章
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中文摘要
青少年特发性脊柱侧凸(AIS)是一种好发于青春期的常见脊柱慢性疾病。我们先前通过全基因组关联分析研究定位了与汉族AIS发病相关的数个重要易感基因,其中LBX1基因,PAX3基因,和TNIK基因均位于Wnt/β-catenin通路。在对AIS患者两侧椎旁肌的基因表达进行分析后,我们发现AIS患者PAX3以及LBX1的mRNA和蛋白表达较正常人均有显著下降,同时在脊柱凹凸两侧也存在显著表达差异。而其下游基因MyoD表达变化可能导致的肌纤维分布异常亦在AIS患者得到初步证实。因此,我们推断AIS患者MyoD基因受Wnt/β-catenin信号通路基因调控。同时该通路可能影响肌肉和骨骼发育的相互作用,进而参与AIS发病过程。本项目将首次通过细胞学实验和动物模型探索Wnt/β-catenin信号通路基因异常表达对AIS患者椎旁肌发育的调控作用。上述研究成果将进一步揭示AIS发生和进展的分子机制。
英文摘要
Adolescent idiopathic scoliosis (AIS) is a common spinal deformity that occurs in the puberty. We have previously identified several important susceptibility genes related to AIS by genome wide association analysis, of which LBX1, PAX3 and TNIK genes are all located in the Wnt/beta-catenin signal pathway. After analyzing the gene expression of bilateral paraspinal muscles in AIS patients, we found that PAX3 and LBX1 are remarkably down-expressed in AIS patients than in normal controls. Besides, there were significant differences between the concave and the convex side regarding the gene expression. The abnormality of the muscle fiber distribution was also observed in the patients with down-expressed MyoD. Therefore, we speculated that the MyoD gene may be regulated by the Wnt/beta-catenin signaling pathway in AIS patients, which in turn influenced the distribution of muscle fiber in the bilateral paraspinal muscles. Meanwhile, the Wnt/beta-catenin pathway may affect the interaction between muscle and bone development. This project aims to investigate the regulation of asymmetric expression of the Wnt/beta-catenin pathway gene and to clarify its role in the development of bilateral paraspinal muscles in AIS patients through cytological experiments and animal models. Our results will further reveal the molecular mechanism underlying the occurrence and progression of AIS.
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
A Functional SNP in the Promoter of LBX1 Is Associated With the Development of Adolescent Idiopathic Scoliosis Through Involvement in the Myogenesis of Paraspinal Muscles.
LBX1 启动子中的功能性 SNP 通过参与椎旁肌肉的肌生成与青少年特发性脊柱侧弯的发展相关
DOI:10.3389/fcell.2021.777890
发表时间:2021
期刊:Frontiers in cell and developmental biology
影响因子:5.5
作者:Xu L;Feng Z;Dai Z;Lee WYW;Wu Z;Liu Z;Sun X;Tang N;Cheng JC;Qiu Y;Zhu Z
通讯作者:Zhu Z
DOI:10.1097/brs.0000000000003409
发表时间:2020-02
期刊:Spine
影响因子:3
作者:Leilei Xu;Z. Dai;Chao Xia;Zhichong Wu;Zhenhua Feng;Xu Sun;Zhen Liu;Y. Qiu;J. Cheng;Ze-zhang Zhu
通讯作者:Leilei Xu;Z. Dai;Chao Xia;Zhichong Wu;Zhenhua Feng;Xu Sun;Zhen Liu;Y. Qiu;J. Cheng;Ze-zhang Zhu
Novel Mutations in UTS2R are Associated with Adolescent Idiopathic Scoliosis in the Chinese Population
UTS2R的新突变与中国人群中青少年特发性脊柱侧弯有关
DOI:10.1097/brs.0000000000003786
发表时间:2021-03-01
期刊:SPINE
影响因子:3
作者:Dai, Zhicheng;Wang, Yuwen;Zhu, Zezhang
通讯作者:Zhu, Zezhang
拷贝数变异与青少年特发性脊柱侧凸发病的关联及其分子机制研究
  • 批准号:
    81772304
  • 项目类别:
    面上项目
  • 资助金额:
    55.0万元
  • 批准年份:
    2017
  • 负责人:
    朱泽章
  • 依托单位:
全基因组外显子测序技术在Chiari畸形遗传病因学中的应用研究
  • 批准号:
    81371912
  • 项目类别:
    面上项目
  • 资助金额:
    70.0万元
  • 批准年份:
    2013
  • 负责人:
    朱泽章
  • 依托单位:
继发于Chiari畸形的脊柱侧凸病因学研究
  • 批准号:
    81171672
  • 项目类别:
    面上项目
  • 资助金额:
    52.0万元
  • 批准年份:
    2011
  • 负责人:
    朱泽章
  • 依托单位:
国内基金
海外基金