Piezo机械敏感性离子通道在骨关节系统中的作用

Role of Piezo mechanosensitive ion channels in the osteoarticular system

目的总结Piezo机械敏感性离子通道在骨关节系统中的作用,以期为后续研究提供参考。方法广泛查阅国内外相关文献,对Piezo离子通道的结构特点、门控机制、激活剂与阻滞剂及其在骨关节系统中的作用进行总结。结果骨关节系统是机体主要承重和运动组织,其感知并响应机械刺激的能力是维持骨关节正常生理功能的保障之一,许多骨关节疾病的发生、发展与异常机械负荷有紧密关系。目前研究显示Piezo机械敏感性离子通道通过响应拉伸刺激、细胞Ca^(2+)内流信号调节向成骨方向分化;并影响成骨细胞的增殖与迁移,通过成骨细胞-破骨细胞之间细胞交流维持骨内稳态。同时,Piezo1蛋白可以通过其宿主细胞间接参与调控破骨细胞的形成及活性,进而调节骨重塑过程。而Piezo1离子通道在机械刺激时,通过调节Akt、Wnt1信号通路表达,维持骨内稳态;针对Piezo1、2离子通道对高应变机械信号的敏感性,介导的Ca^(2+)内流以及炎症信号使得软骨细胞中Piezo1离子通道机械转导敏感性增加的特性,有望成为靶向性防治骨关节炎的新切入点。但机械刺激如何调控骨关节生理/病理过程仍待阐明。结论Piezo机械敏感性离子通道赋予了骨关节系统感知并响应机械应力的重要能力,在其细胞命运转归、骨骼发育、骨与软骨稳态维持等方面扮演关键的机械传感作用。

Objective To summarize the role of Piezo mechanosensitive ion channels in the osteoarticular system,in order to provide reference for subsequent research.Methods Extensive literature review was conducted to summarize the structural characteristics,gating mechanisms,activators and blockers of Piezo ion channels,as well as their roles in the osteoarticular systems.Results The osteoarticular system is the main load-bearing and motor tissue of the body,and its ability to perceive and respond to mechanical stimuli is one of the guarantees for maintaining normal physiological functions of bones and joints.The occurrence and development of many osteoarticular diseases are closely related to abnormal mechanical loads.At present,research shows that Piezo mechanosensitive ion channels differentiate towards osteogenesis by responding to stretching stimuli and regulating cellular Ca^(2+)influx signals;and it affects the proliferation and migration of osteoblasts,maintaining bone homeostasis through cellular communication between osteoblasts-osteoclasts.Meanwhile,Piezo1 protein can indirectly participate in regulating the formation and activity of osteoclasts through its host cells,thereby regulating the process of bone remodeling.During mechanical stimulation,the Piezo1 ion channel maintains bone homeostasis by regulating the expressions of Akt and Wnt1 signaling pathways.The sensitivity of Piezo1/2 ion channels to high strain mechanical signals,as well as the increased sensitivity of Piezo1 ion channels to mechanical transduction mediated by Ca^(2+)influx and inflammatory signals in chondrocytes,is expected to become a new entry point for targeted prevention and treatment of osteoarthritis.But the specific way mechanical stimuli regulate the physiological/pathological processes of bones and joints still needs to be clarified.Conclusion Piezo mechanosensitive ion channels give the osteoarticular system with important abilities to perceive and respond to mechanical stress,playing a crucial mechanical sensing role in its cellular fate,bone development,and maintenance of bone and cartilage homeostasis.