Circular RNA circ-3626 promotes bone formation by modulating the miR-338-3p/Runx2 axis

Chen, Gaoyang1,3; Wang, Song2,3; Wei, Ruihong1,3; Liu, Yingnan1,3; Xu, Tao1,3; Liu, Zhaokang1,3; Tan, Zhouyong1,3; Xie, Yongheng2,3; Yang, Dazhi2,3; Liang, Zhen4; Zhuang, Yongqing1,3; Peng, Songlin2,3

2024-03-01

10.1016/j.jbspin.2023.105669

JOINT BONE SPINE   影响因子和分区

1297-319X

1778-7254

Objective. - Disorders of bone homeostasis are the key factors leading to metabolic bone disease, such as senile osteoporosis, which is characterized by age-related bone loss. Bone marrow stromal cells (BMSCs) possess high osteogenic capacity which has been regarded as a practical approach to preventing bone loss. Previous studies have shown that the osteogenic differentiation ability of BMSCs is significantly decreased in senile osteoporosis. Recently, circular RNAs (circRNAs) have been regarded as critical regulators in controlling the osteogenic differentiation of BMSCs by sponging microRNAs (miRNAs). Our study aimed to discover new and critical osteogenesis-related circRNAs that can promote bone formation in senile osteoporosis.Methods. - We detected the dysregulated circRNAs of BMSCs upon osteogenic differentiation induction and identified the critical osteogenic circRNA (circ-3626). The relationship between circ-3626 and osteoporosis was further verified in clinical bone samples and aged mice by qPCR. Moreover, circ-3626 AAV was constructed to examine the osteogenic effect of circ-3626 on bone formation via using Micro-CT, double calcein labeling, and the three-point bending tests. Bioinformatics analysis, Luciferase report gene assays, FISH, RNA pull-down, qPCR, Western Blots, and alizarin red staining assay explore the effects and mechanisms of circ-3626 on osteogenic differentiation of BMSCs.Results. - Circ-3626 was identified as a pivotal osteogenesis-related circRNA via RNA sequencing. The results of alizarin red staining, Western blots, and qPCR assays suggest that overexpressing circ-3626 dramatically accelerates the osteogenic capability of BMSCs. Furthermore, the bone repair capability of aging mice could be significantly improved by circ-3626 AAV treatment. Micro RNA miR-338-3p was identified as the downstream target of circ-3626. Overexpression of circ-3626 increases the expression of Runx2 by sponging miR-338-3p, thereby promoting the osteogenic differentiation of BMSCs by upregulating the expression of osteogenic genes. In addition, Western blots, and qPCR assays suggest circ-3626 AAV treatment promote the expression of Runx2 and osteogenic marker genes.Conclusion. - Thus, we demonstrate that circ-3626 plays a pivotal role in promoting bone formation through the miR-338-3p/Runx2 axis and may provide new strategies for preventing and treating the bone loss of senile osteoporosis.(c) 2023 L'Auteur(s). Publie par Elsevier Masson SAS au nom de Societe franc, aise de rhumatologie. Cet article est publie en Open Access sous licence CC BY-NC-ND (http://creativecommons.org/licenses/bync-nd/4.0/).

Bone marrow stromal cells Circ-3626 Age-related osteoporosis miR-338-3p Runx2 Bone formation

SCI

英语

第一 ; 通讯

National Natural Science Foundation of China["82272488","82272458","82302678"] ; Shenzhen Municipal Science and Technology Innovation Committee Project["JCYJ20190806160407178","JCYJ20220530152812028"] ; Shenzhen Medical Academy of Research and Translation Project[A2303029] ; Shenzhen Key Laboratory of Musculoskeletal Tissue Reconstruction and Function Restoration[ZDSYS20200811143752005] ; Sanming Project of Medicine in Shenzhen[SZSM202111015] ; Shenzhen Key Medical Discipline Construction Fund[SZXK024]

Rheumatology

Rheumatology

WOS:001149694000001

ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER

CLINICAL MEDICINE

Web of Science

1.Jinan Univ, Southern Univ Sci & Technol, Shenzhen Peoples Hosp, Affiliated Hosp 1 ,Div Hand Foot & Microvasc Surg,, Shenzhen 518020, Guangdong, Peoples R China
2.Jinan Univ, Affiliated Hosp 1, Shenzhen Peoples Hosp, Dept Orthoped Surg,Div Spine Surg ,Southern Univ S, Shenzhen 518020, Peoples R China
3.Shenzhen Inst Orthoped Res, Key Lab Musculoskeletal Tissue Reconstruct & Funct, Shenzhen 518020, Peoples R China
4.Jinan Univ, Affiliated Hosp 1, Shenzhen Peoples Hosp, Dept Geriatr,Southern Univ Sci & Technol,Clin Med, Shenzhen 518020, Peoples R China

Chen, Gaoyang,Wang, Song,Wei, Ruihong,et al. Circular RNA circ-3626 promotes bone formation by modulating the miR-338-3p/Runx2 axis[J]. JOINT BONE SPINE,2024,91(2).

Chen, Gaoyang.,Wang, Song.,Wei, Ruihong.,Liu, Yingnan.,Xu, Tao.,...&Peng, Songlin.(2024).Circular RNA circ-3626 promotes bone formation by modulating the miR-338-3p/Runx2 axis.JOINT BONE SPINE,91(2).

Chen, Gaoyang,et al."Circular RNA circ-3626 promotes bone formation by modulating the miR-338-3p/Runx2 axis".JOINT BONE SPINE 91.2(2024).