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HuR阳性压力颗粒:与年龄相关的骨质疏松症的潜在目标
Ying Huai1,2,3,4, Xue Wang1,2,3, Wenjing Mao1,2,3
1Lab for Bone Metabolism, Xi'an Key Laboratory of Special Medicine and Health Engineering, Northwestern Polytechnical University, Xi'an, China.
衰老会损害成骨细胞功能和骨转换,导致与年龄相关的骨退行性变。应激颗粒(SGs)是一类无膜细胞器,通过募集RNA结合蛋白(RBPs)在应激条件下组装,近年来被发现是年龄相关疾病中的新机制。本研究鉴定出HuR是一种与骨相关的RBP,可在衰老过程中聚集形成SGs并促进成骨作用。在成骨细胞分化过程中,HuR阳性SG的形成增加,而HuR过表达可缓解衰老成骨细胞中SG形成减少的现象。此外,HuR通过结合并招募β-catenin进入SGs,正向调控其靶基因β-catenin的mRNA稳定性和表达水平。作为潜在的治疗靶点,HuR激活剂芹菜素(API)可增强HuR的表达,从而促进成骨细胞分化。API处理可促进HuR的核输出,增强β-catenin向HuR阳性SGs的募集,促进β-catenin的核转位,并有助于成骨作用。我们的研究揭示了HuR及其SGs在骨骼衰老过程中促进成骨的重要作用,为防治年龄相关性骨骼疾病提供了新的治疗策略基础。
衰老会损害成骨细胞功能和骨转换,导致与年龄相关的骨退行性变。应激颗粒(SGs)是一类无膜细胞器,通过募集RNA结合蛋白(RBPs)在应激条件下组装,近年来被发现是年龄相关疾病中的新机制。本研究鉴定出HuR是一种与骨相关的RBP,可在衰老过程中聚集形成SGs并促进成骨作用。在成骨细胞分化过程中,HuR阳性SG的形成增加,而HuR过表达可缓解衰老成骨细胞中SG形成减少的现象。此外,HuR通过结合并招募β-catenin进入SGs,正向调控其靶基因β-catenin的mRNA稳定性和表达水平。作为潜在的治疗靶点,HuR激活剂芹菜素(API)可增强HuR的表达,从而促进成骨细胞分化。API处理可促进HuR的核输出,增强β-catenin向HuR阳性SGs的募集,促进β-catenin的核转位,并有助于成骨作用。我们的研究揭示了HuR及其SGs在骨骼衰老过程中促进成骨的重要作用,为防治年龄相关性骨骼疾病提供了新的治疗策略基础。
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