Circular RNA circStag1 promotes bone regeneration by interacting with HuR

查看全文 作　　者：Gaoyang [1,2]Chen;Canling [1,2]Long;Shang [1,2]Wang;Zhenmin [1,2]Wang;Xin [1,2]Chen;Wanze [1,2]Tang;Xiaoqin [1,2]He;Zhiteng [1,2]Bao;Baoyu [1,2]Tan;Jin [1,2]Zhao;Yongheng [1,2]Xie;Zhizhong [3]Li;Dazhi [1,2]Yang;Guozhi [4]Xiao;Songlin [1,2]Peng

机构地区：[1]Department of Spine Surgery and Institute for Orthopaedic Research,the Second Clinical Medical College of Jinan University(Shenzhen People’s Hospital),Shenzhen Key Laboratory of Musculoskeletal Tissue Reconstruction and Function Restoration,Shenzhen 518020,China;[2]The First Affiliated Hospital,Southern University of Science and Technology,Shenzhen 518055,China;[3]The First Affiliated Hospital,Jinan University,Guangzhou 510630,China;[4]School of Medicine,Southern University of Science and Technology,Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research,Shenzhen Key Laboratory of Cell Microenvironment,Shenzhen 518055,China

出　　处：《Bone Research》索引2022年第10卷第3期,共13页

基　　金：The Shenzhen Municipal Science and Technology Innovation Committee Project(JCYJ20190806160407178,JCYJ20180305164544288,JSGG20180504170427135,SGLH20180625141602256,JCYJ20180305164659637);the Shenzhen Key Laboratory of Musculoskeletal Tissue Reconstruction and Function Restoration(ZDSYS20200811143752005)supported this work。 摘　　要：Postmenopausal osteoporosis is a common bone metabolic disorder characterized by deterioration of the bone microarchitecture,leading to an increased risk of fractures.Recently,circular RNAs(circ RNAs)have been demonstrated to play pivotal roles in regulating bone metabolism.However,the underlying functions of circ RNAs in bone metabolism in postmenopausal osteoporosis remain obscure.Here,we report that circ Stag1 is a critical osteoporosis-related circ RNA that shows significantly downregulated expression in osteoporotic bone marrow mesenchymal stem cells(BMSCs)and clinical bone tissue samples from patients with osteoporosis.Overexpression of circ Stag1 significantly promoted the osteogenic capability of BMSCs.Mechanistically,we found that circ Stag1 interacts with human antigen R(Hu R),an RNA-binding protein,and promotes the translocation of Hu R into the cytoplasm.A high cytoplasmic level of Hu R led to the activation of the Wnt signaling pathway by stabilizing and enhancing low-density lipoprotein receptor-related protein 5/6(Lrp5/6)andβ-catenin expression,thereby stimulating the osteogenic differentiation of BMSCs.Furthermore,overexpression of circ Stag1 in vivo by circ Stag1-loaded adeno-associated virus(circ Stag1-AAV)promoted new bone formation,thereby preventing bone loss in ovariectomized rats.Collectively,we show that circ Stag1 plays a pivotal role in promoting the regeneration of bone tissue via Hu R/Wnt signaling,which may provide new strategies to prevent bone metabolic disorders such as postmenopausal osteoporosis. 关键词：METABOLISM thereby promoted

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Circular RNA circStag1 promotes bone regeneration by interacting with HuR

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