中国组织工程研究 ›› 2023, Vol. 27 ›› Issue (17): 2716-2722.doi: 10.12307/2023.404

• 组织构建综述 tissue construction review • 上一篇    

Piezo1介导的机械应力刺激在抗骨质疏松中的作用

黄浩然1,卫杨文祥1,章家皓1,莫  亮1,刘予豪2,陈镇秋2,王海彬2,周  驰2   

  1. 1广州中医药大学第一临床医学院,广东省广州市  510405;2广州中医药大学第一附属医院,广东省广州市  510405
  • 收稿日期:2022-06-09 接受日期:2022-07-06 出版日期:2023-06-18 发布日期:2022-10-25
  • 通讯作者: 周驰,医学博士,副主任医师,广州中医药大学第一附属医院,广东省广州市 510405
  • 作者简介:黄浩然,男,1994年生,广东省阳春市人,汉族,广州中医药大学在读硕士,主要从事中医药防治骨与关节疾病研究。
  • 基金资助:
    2021年国家自然科学基金项目(82074462),项目负责人:王海彬;2021年国家自然科学基金项目(82104883),项目负责人:刘予豪;2021年度广东省普通高校特色创新类项目(2021KTSCX021),项目负责人:周驰;2021年广州市科技计划项目(202102020930),项目负责人:刘予豪;广州中医药大学“双一流”与高水平大学学科协同创新团队项目(2021xk46),项目负责人:陈镇秋

Piezo1-mediated mechanical stress stimulation in anti-osteoporosis treatment

Huang Haoran1, Wei Yangwenxiang1, Zhang Jiahao1, Mo Liang1, Liu Yuhao2, Chen Zhenqiu2, Wang Haibin2, Zhou Chi2   

  1. 1First School of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong Province, China; 2First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong Province, China
  • Received:2022-06-09 Accepted:2022-07-06 Online:2023-06-18 Published:2022-10-25
  • Contact: Zhou Chi, MD, Associate chief physician, First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong Province, China
  • About author:Huang Haoran, Master candidate, First School of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong Province, China
  • Supported by:
    the National Natural Science Foundation of China in 2021, No. 82074462 (to WHB) and 82104883 (to LYH); Guangdong Province General Universities Characteristic Innovation Project in 2021, No. 2021KTSCX021 (to ZC); Guangzhou Municipal Science and Technology Project, No. 202102020930 (to LYH); “Double First-Class” and High-Level University Discipline Collaborative Innovation Team Project of Guangzhou University of Chinese Medicine, No. 2021xk46 (to CZQ)

摘要:

文题释义:
Piezo1:是一种以三叶螺旋桨状三聚体构造为基本结构的机械敏感阳离子通道蛋白,在肺、肾、膀胱、血管及骨骼中均有表达,能将物理的机械力转化成生物电信号,在多种病理生理过程中发挥重要的调节作用,如骨骼发育、血管生成和免疫应答等。
机械应力:多细胞生物中的细胞持续暴露于细胞外部或内部的机械力中,产生和响应机械力的能力是生物体发育、生命和生存的基本要求。骨组织对机械应力刺激非常敏感,机械应力的卸载和加载分别与骨吸收和骨形成功能密切相关。

背景:机械敏感通道蛋白Piezo1是机械应力刺激的重要靶蛋白,能将物理的机械力转化成生物电信号,从而调控骨形成与骨吸收,在抗骨质疏松中发挥着重要作用。
目的:总结机械应力刺激在抗骨质疏松中的作用机制、Piezo1分子生物学研究进程及Piezo1在骨质疏松中的研究进展。
方法:使用计算机在中国知网、万方、维普、PubMed及Web of Science数据库进行文献检索,中文检索词为“骨质疏松、Piezo1、机械应力、骨”,英文检索词为“osteoporosis,Piezo1,mechanical,osteoblast,osteoclast,chondrocyte,bone”,根据纳排标准对文献进行筛选,最终纳入65篇文献进行综述。
结果与结论:①机械敏感通道蛋白Piezo1的蛋白结构在冷冻电镜技术突破中不断得到新的解析,目前研究表明Piezo1蛋白基于三叶螺旋桨状三维构造主体,在静默和应激状态下可表现出不同的结构变化;②Piezo1介导的机械应力刺激能通过调控成骨细胞、软骨细胞、内皮细胞、肠道细胞的功能影响骨形成,同时调控破骨细胞的功能影响骨吸收,进而在抗骨质疏松中发挥重要作用;③Piezo1介导的机械应力刺激主要通过Wnt/β-catenin信号通路调控成骨细胞功能影响骨形成;而其对破骨细胞功能的调节,因机械力的类型、大小、作用时间的不同而对骨吸收有双向调节作用,需进一步量化的研究;④未来基于Piezo1在骨质疏松中的临床研究、骨质疏松动物模型研究、破骨细胞的相关机制及新型复合材料研究仍需更多的关注。
https://orcid.org/0000-0002-6450-2486(黄浩然)
中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程

关键词: 骨质疏松, 机械应力, Piezo1, 成骨细胞, 破骨细胞, 软骨细胞, 巨噬细胞, 内皮细胞, 肠道细胞

Abstract: BACKGROUND: Piezo1 is a mechanosensitive channel that acts as an important target protein for mechanical stress stimulation. Piezo1 converts external mechanical forces into biological signals, regulating bone formation and bone resorption. Piezo1 plays an important role in anti-osteoporosis.
OBJECTIVE: To summarize the mechanism of mechanical stress stimulation in anti-osteoporosis and research progress in Piezo1 molecular biology as well as the use of Piezo1 in the treatment of osteoporosis.
METHODS: Relevant literature was retrieved in CNKI, WanFang, VIP, PubMed, and Web of Science databases using computers. The search terms were “osteoporosis, Piezo1, mechanical, osteoblast, osteoclast, chondrocyte, bone” in Chinese and English. Finally, 65 documents were included for review according to the inclusion and exclusion criteria.
RESULTS AND CONCLUSION: The structure of Piezo1 has been continuously analyzed in the breakthrough of cryo-electron microscopy. Based on a three-bladed propeller 3D structure, Piezo1 exhibits different structural changes under silent and stressful states. Piezo1-mediated mechanical stress stimulation can affect bone formation by regulating the functions of osteoblasts, chondrocytes, endothelial cells and intestinal cells, and simultaneously affect bone resorption by regulating the function of osteoclasts, thereby playing an important role in anti-osteoporosis. Piezo1-mediated mechanical stress mainly affects bone formation by regulating the function of osteoblasts through the Wnt/β-catenin signaling pathway. And it has a two-way regulatory effect on osteoclasts due to different type, strength, and duration of mechanical force, which needs to be further quantified. For the use of Piezo1 in the treatment of osteoporosis, emphasis should be placed on clinical and animal model research for osteoporosis, osteoclast-related mechanisms, and new composite materials.

Key words: osteoporosis, mechanical stress, Piezo1, osteoblast, osteoclast, chondrocyte, macrophage, endothelial cell, intestinal cell

中图分类号: