PMID- 35361779 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220423 IS - 2095-4700 (Print) IS - 2095-6231 (Electronic) IS - 2095-4700 (Linking) VI - 10 IP - 1 DP - 2022 Mar 31 TI - Circular RNA circStag1 promotes bone regeneration by interacting with HuR. PG - 32 LID - 10.1038/s41413-022-00208-x [doi] LID - 32 AB - 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 (circRNAs) have been demonstrated to play pivotal roles in regulating bone metabolism. However, the underlying functions of circRNAs in bone metabolism in postmenopausal osteoporosis remain obscure. Here, we report that circStag1 is a critical osteoporosis-related circRNA that shows significantly downregulated expression in osteoporotic bone marrow mesenchymal stem cells (BMSCs) and clinical bone tissue samples from patients with osteoporosis. Overexpression of circStag1 significantly promoted the osteogenic capability of BMSCs. Mechanistically, we found that circStag1 interacts with human antigen R (HuR), an RNA-binding protein, and promotes the translocation of HuR into the cytoplasm. A high cytoplasmic level of HuR led to the activation of the Wnt signaling pathway by stabilizing and enhancing low-density lipoprotein receptor-related protein 5/6 (Lrp5/6) and beta-catenin expression, thereby stimulating the osteogenic differentiation of BMSCs. Furthermore, overexpression of circStag1 in vivo by circStag1-loaded adeno-associated virus (circStag1-AAV) promoted new bone formation, thereby preventing bone loss in ovariectomized rats. Collectively, we show that circStag1 plays a pivotal role in promoting the regeneration of bone tissue via HuR/Wnt signaling, which may provide new strategies to prevent bone metabolic disorders such as postmenopausal osteoporosis. CI - (c) 2022. The Author(s). FAU - Chen, Gaoyang AU - Chen G AD - 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. AD - The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, 518055, China. FAU - Long, Canling AU - Long C AD - 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. AD - The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, 518055, China. FAU - Wang, Shang AU - Wang S AD - 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. AD - The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, 518055, China. FAU - Wang, Zhenmin AU - Wang Z AD - 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. AD - The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, 518055, China. FAU - Chen, Xin AU - Chen X AD - 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. AD - The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, 518055, China. FAU - Tang, Wanze AU - Tang W AD - 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. AD - The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, 518055, China. FAU - He, Xiaoqin AU - He X AD - 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. AD - The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, 518055, China. FAU - Bao, Zhiteng AU - Bao Z AD - 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. AD - The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, 518055, China. FAU - Tan, Baoyu AU - Tan B AD - 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. AD - The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, 518055, China. FAU - Zhao, Jin AU - Zhao J AD - 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. AD - The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, 518055, China. FAU - Xie, Yongheng AU - Xie Y AD - 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. AD - The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, 518055, China. FAU - Li, Zhizhong AU - Li Z AD - The First Affiliated Hospital, Jinan University, Guangzhou, 510630, China. FAU - Yang, Dazhi AU - Yang D AD - 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. yangdazhi1111@163.com. AD - The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, 518055, China. yangdazhi1111@163.com. FAU - Xiao, Guozhi AU - Xiao G AUID- ORCID: 0000-0002-4269-2450 AD - 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. xiaogz@sustech.edu.cn. FAU - Peng, Songlin AU - Peng S AUID- ORCID: 0000-0002-4042-7071 AD - 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. dyffyy2@mail.sustech.edu.cn. AD - The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, 518055, China. dyffyy2@mail.sustech.edu.cn. LA - eng GR - JCYJ20180305164659637/Shenzhen Science and Technology Innovation Commission/ GR - SGLH20180625141602256/Shenzhen Science and Technology Innovation Commission/ GR - JSGG20180504170427135/Shenzhen Science and Technology Innovation Commission/ GR - JCYJ20180305164544288/Shenzhen Science and Technology Innovation Commission/ GR - JCYJ2017041362104773/Shenzhen Science and Technology Innovation Commission/ GR - ZDSYS20200811143752005/Shenzhen Science and Technology Innovation Commission/ GR - ZDSYS20200811143752005/Shenzhen Science and Technology Innovation Commission/ GR - ZDSYS20200811143752005/Shenzhen Science and Technology Innovation Commission/ GR - ZDSYS20200811143752005/Shenzhen Science and Technology Innovation Commission/ GR - ZDSYS20200811143752005/Shenzhen Science and Technology Innovation Commission/ GR - ZDSYS20200811143752005/Shenzhen Science and Technology Innovation Commission/ GR - ZDSYS20200811143752005/Shenzhen Science and Technology Innovation Commission/ GR - ZDSYS20200811143752005/Shenzhen Science and Technology Innovation Commission/ GR - ZDSYS20200811143752005/Shenzhen Science and Technology Innovation Commission/ GR - ZDSYS20200811143752005/Shenzhen Science and Technology Innovation Commission/ GR - ZDSYS20200811143752005/Shenzhen Science and Technology Innovation Commission/ GR - ZDSYS20200811143752005/Shenzhen Science and Technology Innovation Commission/ GR - JCYJ20180305164659637/Shenzhen Science and Technology Innovation Commission/ GR - SGLH20180625141602256/Shenzhen Science and Technology Innovation Commission/ GR - ZDSYS20200811143752005/Shenzhen Science and Technology Innovation Commission/ PT - Journal Article DEP - 20220331 PL - China TA - Bone Res JT - Bone research JID - 101608652 PMC - PMC8971384 COIS- The authors declare no competing interests. EDAT- 2022/04/02 06:00 MHDA- 2022/04/02 06:01 PMCR- 2022/03/31 CRDT- 2022/04/01 05:35 PHST- 2021/07/16 00:00 [received] PHST- 2022/02/28 00:00 [accepted] PHST- 2022/01/29 00:00 [revised] PHST- 2022/04/01 05:35 [entrez] PHST- 2022/04/02 06:00 [pubmed] PHST- 2022/04/02 06:01 [medline] PHST- 2022/03/31 00:00 [pmc-release] AID - 10.1038/s41413-022-00208-x [pii] AID - 208 [pii] AID - 10.1038/s41413-022-00208-x [doi] PST - epublish SO - Bone Res. 2022 Mar 31;10(1):32. doi: 10.1038/s41413-022-00208-x.