circ_0003204 regulates the osteogenic differentiation of human adipose-derived stem cells via miR-370-3p/HDAC4 axis.
10.1038/s41368-022-00184-2
- Author:
Liyuan YU
1
;
Kai XIA
1
;
Jing ZHOU
2
;
Zhiai HU
1
;
Xing YIN
1
;
Chenchen ZHOU
3
;
Shujuan ZOU
4
;
Jun LIU
5
Author Information
1. State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
2. Department of Stomatology, Kunming Yan'an hospital, Kunming, China.
3. State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
4. State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China. shujuanzou@aliyun.com.
5. State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China. junliu@scu.edu.cn.
- Publication Type:Research Support, Non-U.S. Gov't
- MeSH:
Adipose Tissue/metabolism*;
Animals;
Cell Differentiation/genetics*;
Cells, Cultured;
Histone Deacetylases/metabolism*;
Humans;
Mice;
MicroRNAs/metabolism*;
Osteogenesis/genetics*;
RNA, Circular/metabolism*;
Repressor Proteins/metabolism*;
Signal Transduction;
Stem Cells/metabolism*
- From:
International Journal of Oral Science
2022;14(1):30-30
- CountryChina
- Language:English
-
Abstract:
Human adipose-derived stem cells (hASCs) are a promising cell type for bone tissue regeneration. Circular RNAs (circRNAs) have been shown to play a critical role in regulating various cell differentiation and involve in mesenchymal stem cell osteogenesis. However, how circRNAs regulate hASCs in osteogenesis is still unclear. Herein, we found circ_0003204 was significantly downregulated during osteogenic differentiation of hASCs. Knockdown of circ_0003204 by siRNA or overexpression by lentivirus confirmed circ_0003204 could negatively regulate the osteogenic differentiation of hASCs. We performed dual-luciferase reporting assay and rescue experiments to verify circ_0003204 regulated osteogenic differentiation via sponging miR-370-3p. We predicted and confirmed that miR-370-3p had targets in the 3'-UTR of HDAC4 mRNA. The following rescue experiments indicated that circ_0003204 regulated the osteogenic differentiation of hASCs via miR-370-3p/HDAC4 axis. Subsequent in vivo experiments showed the silencing of circ_0003204 increased the bone formation and promoted the expression of osteogenic-related proteins in a mouse bone defect model, while overexpression of circ_0003204 inhibited bone defect repair. Our findings indicated that circ_0003204 might be a promising target to promote the efficacy of hASCs in repairing bone defects.