HuR-mediated nucleocytoplasmic translocation of HOTAIR relieves its inhibition of osteogenic differentiation and promotes bone formation  

作　　者：Yuheng Li Weijia Sun Jianwei Li Ruikai Du Wenjuan Xing Xinxin Yuan Guohui Zhong Dingsheng Zhao Zizhong Liu Xiaoyan Jin Junjie Pan Youyou Li Qi Li Guanghan Kan Xuan Han Shukuan Ling Xiqing Sun Yingxian Li 

机构地区：[1]The Key Laboratory of Aerospace Medicine,Ministry of Education,The Fourth Military Medical University,Xi’an,Shaanxi,China [2]State Key Laboratory of Space Medicine Fundamentals and Application,China Astronaut Research and Training Center,Beijing,China [3]The Center of Space Bio-Medicine,Beijing Institute of Technology,Beijing,China [4]Medical College of Soochow University,Suzhou,Jiangsu,China [5]Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine,Vision and Brain Health),Wenzhou,Zhejiang,China

出　　处：《Bone Research》2023年第4期803-818,共16页骨研究（英文版）

基　　金：supported by the National Natural Science Foundation of China Project(No.82072108,82192880,82192882,81830061,91740114 and 32000879);the Space Medical Experiment Project of China Manned Space Program(HYZHXM01006);National Key Laboratory of Space Medicine,China Astronaut Research and Training Center(SMFA22Q02)。

摘　　要：Bone marrow mesenchymal stem cell(BMSC)osteogenic differentiation and osteoblast function play critical roles in bone formation,which is a highly regulated process.Long noncoding RNAs(lncRNAs)perform diverse functions in a variety of biological processes,including BMSC osteogenic differentiation.Although several studies have reported that HOX transcript antisense RNA(HOTAIR)is involved in BMSC osteogenic differentiation,its effect on bone formation in vivo remains unclear.Here,by constructing transgenic mice with BMSC(Prx1-HOTAIR)-and osteoblast(Bglap-HOTAIR)-specific overexpression of HOTAIR,we found that Prx1-HOTAIR and Bglap-HOTAIR transgenic mice show different bone phenotypes in vivo.Specifically,Prx1-HOTAIR mice showed delayed bone formation,while Bglap-HOTAIR mice showed increased bone formation.HOTAIR inhibits BMSC osteogenic differentiation but promotes osteoblast function in vitro.Furthermore,we identified that HOTAIR is mainly located in the nucleus of BMSCs and in the cytoplasm of osteoblasts.HOTAIR displays a nucleocytoplasmic translocation pattern during BMSC osteogenic differentiation.We first identified that the RNA-binding protein human antigen R(HuR)is responsible for HOTAIR nucleocytoplasmic translocation.HOTAIR is essential for osteoblast function,and cytoplasmic HOTAIR binds to miR-214 and acts as a ceRNA to increase Atf4 protein levels and osteoblast function.BglapHOTAIR mice,but not Prx1-HOTAIR mice,showed alleviation of bone loss induced by unloading.This study reveals the importance of temporal and spatial regulation of HOTAIR in BMSC osteogenic differentiation and bone formation,which provides new insights into precise regulation as a target for bone loss.

关 键 词：HOTAIR PRECISE function 

分 类 号：R68[医药卫生—骨科学]