Piezo1在骨稳态中的作用机制与研究进展  

The mechanism and research progress of Piezo1 in bone homeostasis

作　　者：李朝民 赵滨 褚美玲 杨光华[1] Li Chaomin;Zhao Bin;Chu Meiling;Yang Guanghua(Department of General Surgery,the Seventh People's Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200137,China)

机构地区：[1]上海中医药大学附属第七人民医院普外科,上海200137

出　　处：《中华骨科杂志》2025年第5期317-326,共10页Chinese Journal of Orthopaedics

基　　金：上海市卫生健康系统重点学科建设项目(2024ZDXK0051);上海市浦东新区优秀青年医学人才项目(PWRq2024-46)。

摘　　要：骨骼的生长、萎缩与其所承受的机械应力紧密相关。机械传导作为一种基础的生物信号传递机制,涉及细胞通过分泌蛋白质因子和信号通路等媒介,将外部机械力转化为细胞内的信号反应。Piezo1通道能够感知机械应力(如压力、牵张力和剪切力等)使Ca 2+内流,并将其转化为细胞内信号,从而在骨稳态中发挥重要作用。Piezo1通道由Fam38A基因编码,具有独特的38个跨膜螺旋结构,形成碗状三聚体螺旋桨状结构。这种特殊的结构能使其作为机械换能器,感受细胞膜的机械应力刺激并将这些机械信号传输到细胞中。在骨骼系统中Piezo1通过调节巨噬细胞、骨髓间质干细胞、软骨细胞、骨细胞、成骨细胞和破骨细胞的功能,以及通过信号通路如Akt、Wnt/β-catenin、转化生长因子β(TGF-β)和MAPK等,参与维持骨骼形成与吸收的动态平衡。此外,Piezo1的基因多态性与骨密度的明显关联和通过成骨-成血管耦合机制,揭示了其在骨质疏松症治疗中的潜在应用。通过综述Piezo1机械敏感离子通道在骨稳态中的作用机制和最新研究进展阐明Piezo1在骨代谢中的作用,旨在为临床实践中预防和治疗骨质疏松症和其他骨相关疾病提供理论基础和潜在策略。The growth and atrophy of bones are closely related to the mechanical stress they experience.Mechanotransduction,a fundamental biological signal transmission mechanism,enables cells to convert external mechanical forces into intracellular signaling responses through the secretion of protein factors and activation of signaling pathways.Piezo1 is a mechanosensitive ion channel that detects mechanical stress(such as pressure,stretch,and shear force),induces Ca 2+influx,and transduces these signals into intracellular responses,playing a crucial role in bone homeostasis.Encoded by the Fam38A gene,Piezo1 possesses a distinctive 38-transmembrane helical structure that forms a bowl-shaped,trimeric propeller-like configuration.This unique structure allows it to function as a mechanical transducer,sensing mechanical stimuli at the cell membrane and transmitting mechanical signals.In the skeletal system,Piezo1 contributes to maintaining the dynamic balance between bone formation and resorption by regulating the functions of macrophages,bone marrow mesenchymal stem cells,chondrocytes,osteocytes,osteoblasts,and osteoclasts,as well as through signaling pathways such as Akt,Wnt/β-catenin,TGF-β,and MAPK.Additionally,studies have demonstrated a significant association between Piezo1 gene polymorphisms and bone mineral density,highlighting its potential therapeutic applications in osteoporosis treatment via the osteogenic-angiogenic coupling mechanism.This review summarizes the mechanisms and recent research progress on the Piezo1 mechanosensitive ion channel in bone homeostasis.By elucidating Piezo1’s role in bone metabolism,this review aims to provide a theoretical foundation and potential strategies for the prevention and treatment of osteoporosis and other bone-related diseases in clinical practice.

关 键 词：骨质疏松 应力 物理 离子通道 Piezo1 骨稳态 

分 类 号：R681[医药卫生—骨科学]