可降解镁金属通过Ptc调控Hedgehog-Alternative Wnt通路促进牵张成骨的机制研究

批准号:
81974325
项目类别:
面上项目
资助金额:
55.0 万元
负责人:
韩培
依托单位:
学科分类:
骨、关节、软组织医用材料
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
韩培
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中文摘要
牵张成骨是治疗复杂骨缺损的有效方法,新骨形成不良是该技术临床应用中亟待解决的问题。课题组前期在高纯镁棒导向大鼠股骨牵张成骨中发现新骨钙化显著增快。通过转录组测序和生信分析并结合验证结果提出镁调节膜蛋白Ptc对Smo的抑制从而激活Hedgehog通路,并启动Alternative Wnt通路加速牵张成骨钙化过程的机制假说。本项目拟通过细胞和动物牵张模型,明确镁对牵张应力下Hedgehog-Alternative Wnt通路的调控规律;通过相应通路靶点抑制和激动干预,阐明镁对通路关键靶点调节作用的证据;建立条件敲除小鼠模型,验证Ptc蛋白是否为镁加速牵张成骨钙化的始动环节;最后通过分子动力学模型探索镁对Ptc蛋白构像变化影响及靶点,从分子水平上探究镁具体调控机制和方式。通过上述研究,有望阐明镁调节牵张成骨钙化分子机制,为镁材料导向这一创新方法克服临床牵张成骨关键难点提供重要的理论依据。
英文摘要
Distraction osteogenesis is a surgical technique that effectively used in treatment of bone defects, poor bone formation is an urgent problem to be solved in the clinical application of this technology. In previous studies,we found that the high-purity magnesium rod can significantly increase the new bone calcification in the rat femur distraction osteogenesis model. In the subsequent high-throughput transcriptome sequencing(RNA-seq), bioinformatics analysis and further investment , the Hedgehog signaling pathway and the Alternative Wnt signaling pathway were found to be activated. Based on the experimental results, we propose a hypothesis that magnesium binding to Ptc on the cell surface relieves the inhibition of Smo and activates the Hedgehog pathway,this further promotes the new bone regeneration and calcification through the Alternative Wnt pathway. Based on this, we aims to observe the regulation of magnesium ion on Hedgehog-Alternative Wnt signaling pathway in mesenchymal stem cells under distraction stress in vitro.; The magnesium rod was placed in the rat femur distraction model, and the selective inhibitor and gene overexpression vectors were injected locally to verify the regulation of Hedgehog-Alternative Wnt pathway;Through conditional gene knockout animal distraction osteogenesis model, further investigate magnesium regulation of distraction osteogenesis through the Hedgehog-Alternative Wnt pathway;The effects of magnesium on the conformational changes of Ptc protein and its binding site were observed by molecular dynamics stimulation and Spectroscopy. Through the above studies, it is expected to clarify the molecular mechanism of the magnesium in regulation of distraction osteogenesis calcification, and provide an important theoretical basis for the innovative approach of magnesium material to overcome the key difficulties of clinical distraction osteogenesis.
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
High-purity magnesium pin enhances bone consolidation in distraction osteogenesis via regulating Ptch protein activating Hedgehog-alternative Wnt signaling.
高纯度镁针通过调节 Ptch 蛋白激活 Hedgehog-alternative Wnt 信号来增强牵引成骨过程中的骨巩固
DOI:10.1016/j.bioactmat.2020.11.008
发表时间:2021-06
期刊:Bioactive materials
影响因子:18.9
作者:Hamushan M;Cai W;Zhang Y;Ren Z;Du J;Zhang S;Zhao C;Cheng P;Zhang X;Shen H;Han P
通讯作者:Han P
DOI:10.1111/os.13309
发表时间:2022-07
期刊:ORTHOPAEDIC SURGERY
影响因子:2.1
作者:Wu, Yuan-jian;Zhang, Yu-bo;Hamushan, Musha;Zhang, Wen-jun;Zhang, Tao;Li, Xu-jun;Han, Pei;Lou, Teng-fei
通讯作者:Lou, Teng-fei
DOI:10.1021/acscentsci.3c00499
发表时间:2023-07-26
期刊:ACS CENTRAL SCIENCE
影响因子:18.2
作者:Jiang, Feng;Chen, Yingjia;Yu, Jinlong;Zhang, Feiyang;Liu, Qian;He, Lei;Musha, Hamushan;Du, Jiafei;Wang, Boyong;Han, Pei;Chen, Xiaohua;Tang, Jin;Li, Min;Shen, Hao
通讯作者:Shen, Hao
The Role of Staphylococcal Biofilm on the Surface of Implants in Orthopedic Infection.
葡萄球菌生物膜在骨科感染中植入物表面的作用。
DOI:10.3390/microorganisms10101909
发表时间:2022-09-26
期刊:MICROORGANISMS
影响因子:4.5
作者:Lu, Yu;Cai, Wei-jie;Ren, Zun;Han, Pei
通讯作者:Han, Pei
Novel piston technique versus Ilizarov technique for the repair of bone defect after lower limb infection.
新型活塞技术与Ilizarov技术比较修复下肢感染后骨缺损
DOI:10.1186/s13018-021-02844-1
发表时间:2021-12-04
期刊:Journal of orthopaedic surgery and research
影响因子:2.6
作者:Du J;Yin Z;Cheng P;Han P;Shen H
通讯作者:Shen H
国内基金
海外基金
