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Original Article | Open Access

Circular RNA circStag1 promotes bone regeneration by interacting with HuR

Gaoyang Chen1,2,, Canling Long1,2,, Shang Wang1,2, Zhenmin Wang1,2, Xin Chen1,2, Wanze Tang1,2, Xiaoqin He1,2, Zhiteng Bao1,2, Baoyu Tan1,2, Jin Zhao1,2, Yongheng Xie1,2, Zhizhong Li3, Dazhi Yang1,2( ), Guozhi Xiao4 ( ), Songlin Peng1,2 ( )
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
The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen 518055, China
The First Affiliated Hospital, Jinan University, Guangzhou 510630, China
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

These authors contributed equally: Gaoyang Chen, Canling Long.

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Abstract

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 β-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.

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Bone Research
Volume 10,
December 2022
Article number: 32
DOI: 10.1038/s41413-022-00208-x
Cite this article:
Chen G, Long C, Wang S, et al. Circular RNA circStag1 promotes bone regeneration by interacting with HuR. Bone Research, 2022, 10: 32. https://doi.org/10.1038/s41413-022-00208-x

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Received: 16 July 2021
Revised: 29 January 2022
Accepted: 28 February 2022
Published: 31 March 2022
© The Author(s) 2022

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