Circular RNA circStag1 promotes bone regeneration by interacting with HuR

Chen, Gaoyang1,2,3; Long, Canling1,2,3; Wang, Shang1,2,3; Wang, Zhenmin1,2,3; Chen, Xin1,2,3; Tang, Wanze1,2,3; He, Xiaoqin1,2,3; Bao, Zhiteng1,2,3; Tan, Baoyu1,2,3; Zhao, Jin1,2,3; Xie, Yongheng1,2,3; Li, Zhizhong4; Yang, Dazhi1,2,3; Xiao, Guozhi5; Peng, Songlin1,2,3

2022-03-31

10.1038/s41413-022-00208-x

Bone Research   影响因子和分区

2095-4700

2095-6231

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.

SCI

英语

通讯

Shenzhen Municipal Science and Technology Innovation Committee Project["JCYJ20190806160407178","JCYJ20180305164544288","JSGG20180504170427135","SGLH20180625141602256","JCYJ20180305164659637"] ; Shenzhen Key Laboratory of Musculoskeletal Tissue Reconstruction and Function Restoration[ZDSYS20200811143752005]

Cell Biology

Cell & Tissue Engineering

WOS:000776736400001

SPRINGERNATURE

2-s2.0-85127378226

Web of Science

1.Jinan Univ, Shenzhen Key Lab Musculoskeletal Tissue Reconstru, Shenzhen Peoples Hosp, Dept Spine Surg, Shenzhen 518020, Peoples R China
2.Jinan Univ, Shenzhen Key Lab Musculoskeletal Tissue Reconstru, Shenzhen Peoples Hosp, Inst Orthopaed Res,Clin Med Coll 2, Shenzhen 518020, Peoples R China
3.Southern Univ Sci & Technol, Affiliated Hosp 1, Shenzhen 518055, Peoples R China
4.Jinan Univ, Affiliated Hosp 1, Guangzhou 510630, Peoples R China
5.Southern Univ Sci & Technol, Sch Med, Guangdong Prov Key Lab Cell Microenvironm & Dis R, Shenzhen Key Lab Cell Microenvironm, Shenzhen 518055, Peoples R China

Chen, Gaoyang,Long, Canling,Wang, Shang,et al. Circular RNA circStag1 promotes bone regeneration by interacting with HuR[J]. Bone Research,2022,10(1).

Chen, Gaoyang.,Long, Canling.,Wang, Shang.,Wang, Zhenmin.,Chen, Xin.,...&Peng, Songlin.(2022).Circular RNA circStag1 promotes bone regeneration by interacting with HuR.Bone Research,10(1).

Chen, Gaoyang,et al."Circular RNA circStag1 promotes bone regeneration by interacting with HuR".Bone Research 10.1(2022).