课题基金基金详情
基于MIF的WNT/p38 MAPK/NF-κB信号环在炎症条件下对成骨破骨耦联的调控作用
结题报告
批准号:
81772367
项目类别:
面上项目
资助金额:
55.0 万元
负责人:
徐永清
学科分类:
H0606.骨、关节、软组织感染
结题年份:
2021
批准年份:
2017
项目状态:
已结题
项目参与者:
王毅、金涛、何晓清、宋慕国、陆华拓、任莉荣、白继岳、刘帅
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中文摘要
炎症条件下的骨重塑是多信号通路相互影响作用的复杂调控结果。迄今为止,未见把多信号通路相互影响、作用作为整体来探讨对炎症条件下成骨破骨耦联调控的相关报道。巨噬细胞移动抑制因子(MIF)已被证实参与炎症条件下的成骨破骨过程,但具体机制并不完全清楚。此外,研究报道p38 MAPK和NF-κB信号被激活后抑制骨生成。课题组前期报道非经典WNT信号在炎症条件下能促进骨生成,并能正向促进经典WNT信号同时抑制NF-κB通路,而此时p38 MAPK信号也被激活;在这一过程中,MIF表达水平随SPA浓度增高而升高然后迅速下降。因此,我们推测WNT信号、p38 MAPK及NF-κB相互影响作用,可能共同参与了炎症下的成骨破骨过程调控。本研究拟通过探讨炎症条件下MIF介导的多条信号通路相互调节作用(信号环)对成骨破骨耦联的调控,揭示骨感染重塑过程中的病理生理机制,以期为相关疾病的防治提供实验依据和新思路。
英文摘要
Under inflammatory condition, the process of bone remodeling is the results of multiple signals’ complex regulation, in which they interact and afect each other. So far, relevant study has not published,in which interating and affecting among these multiple signals are not used in investigating the unbanlance between the coupling of bosteogenesis and osteoclastogenesis under inflammatory condition. Macrophage migration inhibition factor (MIF) has been confirmed to participate the osteogenesis & osteoclastogenesis process under inflammatory condition, but the specific character is not entirely clear. Moreover, studies have reported that p38 MAPK and NF-κB signal indicate inhibiting bone formation after being activation. our research group has reported that noncanonical WNT signal positively regulate canonical WNT signal, and inhibits NF-κB signal by negative feedback, meanwhile p38 MAPK signal pathway is also activated. During the whole process, MIF factor level firstly elevates gradually and descends in subsequent time. Hence, we speculate that WNT signal, p38 MAPK signal and NF-κB signal pathway integrate and affect each other and regulate bosteogenesis and osteoclastogenesis process together under inflammatory condition. This study is aimed at revealing the pathophysiologic mechanism of bone remodeling process in bone infection by investigating the regulation role (signal loop) within each other among the multiple signal pathways mediated by MIF under inflammatory condition , and is expected to provide experimental bases and new ideas for the prevention and treatment of infection relevant bone disease.
巨噬细胞移动抑制因子(MIF)在调节成骨和破骨分化过程中扮演重要角色,但其具体调控机制仍不清楚。申请人前期研究结果表明,SPA介导的炎症条件下 MIF通过上调NF-kB p65的磷酸化水平负调控大鼠骨髓间充质干细胞的成骨分化,动物实验中MIF,NF-kB和p38在感染性环境中骨稳态方面具有重要的作用。本项目将在前期的工作基础上,从分子水平、细胞水平、组织水平探讨细菌感染因素对骨稳态调控;在感染条件下,本研究还结合高通量测序和生物信息学分析,对MIF基因的调控作用机制包括作用靶点、信号通路等进行了深入探索。此研究将为进一步阐明骨髓炎病程发生发展过程、为利用细胞靶点治疗骨髓炎提供新思路。
期刊论文列表
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专利列表
DOI:10.1186/s12891-020-03894-y
发表时间:2021-01-07
期刊:BMC musculoskeletal disorders
影响因子:2.3
作者:Xu YQ;Fan XY;He XQ;Wen HJ
通讯作者:Wen HJ
DOI:10.1186/s13018-022-02980-2
发表时间:2022-02-19
期刊:Journal of orthopaedic surgery and research
影响因子:2.6
作者:Shi X;Wu Y;Ni H;Li M;Zhang C;Qi B;Wei M;Wang T;Xu Y
通讯作者:Xu Y
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影响因子:--
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影响因子:3.1
作者:Hong-jie Wen;Zhong Chen;Yi Cui;Yongqing Xu
通讯作者:Hong-jie Wen;Zhong Chen;Yi Cui;Yongqing Xu
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