Hippo信号通路中的核心因子YAP/TAZ参与骨形成的作用与机制  

YAP/TAZ,a core factor of the Hippo signaling pathway,is involved in bone formation

作　　者：杨芷姗 唐正龙 Yang Zhishan;Tang Zhenglong(School of Stomatology of Guizhou Medical University,Guiyang 550001,Guizhou Province,China;Hospital of Stomatology of Guizhou Medical University,Guiyang 550001,Guizhou Province,China)

机构地区：[1]贵州医科大学口腔医学院,贵州省贵阳市550001 [2]贵州医科大学附属口腔医院,贵州省贵阳市550001

出　　处：《中国组织工程研究》2023年第8期1264-1271,共8页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金地区科学基金(82060197),项目负责人:唐正龙。

摘　　要：背景:随着机械信号在骨骼中的作用研究逐渐增多,作为力学敏感因子的YAP/TAZ也逐渐受到大众关注。现有研究发现YAP/TAZ可能在骨形成的过程中作为一个重要介质参与其中,但具体机制尚不清楚。目的:对YAP/TAZ参与骨形成的最新研究进展进行综述。方法:第一作者以“Hippo pathway,YAP/TAZ,Bone,Osteogenesis”为英文检索词,以“Hippo信号通路、YAP/TAZ、骨骼、成骨”为中文检索词,检索PubMed数据库和中国知网2016年至2022年3月发表的相关文献,对筛选出的文献进行归纳分析。最终纳入56篇相关文献进行综述。结果与结论:①YAP/TAZ作为Hippo通路的核心因子,在其功能调控上具有特殊性,除了在分子水平上可以调控其活性,细胞微环境的改变,如细胞浓度、细胞形状和细胞外基质的刚度也可以促使其活性改变从而发挥不同功能作用。②YAP/TAZ参与成骨信号传导,并且调控也受细胞微环境影响。过表达或沉默细胞中的YAP/TAZ会促使或抑制成骨信号的传导,从而改变细胞分化结局。③YAP/TAZ参与骨组织细胞的成骨过程,并对不同类型的骨组织细胞有不同功能。但对于过表达或沉默YAP/TAZ方法不同,选择观察细胞种属类型差异较大,结果难以统一量化。④动物实验中证实YAP/TAZ对正常骨骼形态及颌面部形态的正常发育有着至关重要的作用,并且在不同成骨分化阶段有着不同的功能。然而对于实验动物敲除YAP/TAZ条件基因不统一、观察时机不一致导致实验成果难以相互比较。YAP/TAZ在骨形成中有着重要地位,但对于其作用机制还有待深入研究,期待后续有学者深入探索其作用机制,并利用其特性在骨性疾病中发挥作用。BACKGROUND:As the role of mechanical signalling in the bone has been increasingly studied,YAP/TAZ as a mechanosensitive factor has gradually attracted public attention.Existing studies have found that YAP/TAZ may be involved as an important mediator in the process of bone formation,but the mechanism is not yet clear.OBJECTIVE:To summarize the latest research on the effects of YAP/TAZ in bone formation.METHODS:The first author used“Hippo pathway,YAP/TAZ,bone,osteogenesis”as English and Chinese search terms to search in the PubMed and CNKI databases for relevant articles published from 2016 to March 2022.After screening and summarizing,56 relevant articles were finally included for review.RESULTS AND CONCLUSION:(1)YAP/TAZ,as the core factor of the Hippo pathway,has special features in its functional regulation.In addition to regulating its activity at the molecular level,changes in the cellular microenvironment,such as cell density,cell shape and extracellular matrix stiffness,can also contribute to its altered activity and thus YAP/TAZ can play different functional roles.(2)YAP/TAZ is involved in osteogenic signaling and its regulation is also influenced by the cellular microenvironment.Overexpression or silencing of YAP/TAZ in cells can contribute to or inhibit osteogenic signaling,thereby altering the outcome of cell differentiation.(3)YAP/TAZ is involved in the osteogenesis process of bone tissue cells and has different functions for different types of bone tissue cells.However,different methods for overexpressing or silencing YAP/TAZ and different types of cell species selected for observation make it difficult to quantify the results uniformly.(4)In animal experiments,it has been shown that YAP/TAZ is essential for the morphological development of normal bones and maxillofacial regions,and has different functions at different stages of osteogenic differentiation.However,there is no uniformity in the knockout of YAP/TAZ conditional genes in experimental animals and the timing of observations is inconsisten

关 键 词：YAP/TAZ 转化生长因子β 骨形态发生蛋白2 Smads家族 成骨分化 破骨细胞 巨噬细胞 骨骼形态 颌面部畸形 

分 类 号：R459.9[医药卫生—治疗学] R394.2[医药卫生—临床医学] R686.5