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Biomed Pharmacother. 2019 Jul;115:108927. doi: 10.1016/j.biopha.2019.108927. Epub 2019 May 6.

Astragalus polysaccharide promotes proliferation and osteogenic differentiation of bone mesenchymal stem cells by down-regulation of microRNA-152.

Author information

1
Department of Hand Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, China.
2
Department of Breast Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, China.
3
Department of Hand Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, China. Electronic address: wangys042@sohu.com.
4
Department of Hand Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, China. Electronic address: feiqiaotang4393zs@163.com.

Abstract

BACKGROUND/AIMS:

Astragalus polysaccharide (APS) has been clarified to possess antibacterial, antiviral and other activities. MicroRNA-152 (miR-152) is a tumor suppressor, which has been testified to be involved in promoting osteogenic differentiation of marrow mesenchymal stem cells (MSCs). However, whether APS can affect BMSCs proliferation and osteogenic differentiation via mediating miR-152 remains uninvestigated.

METHODS:

After treatment with APS or transfection with pre-miR-152 and anti-miR-152, cell viability, cell proliferation-associated factors, differentiation of BMSCs-related genes, and the relative miR-152 expression was determined by CCK-8, Western blot and qRT-PCR assays. The relationship between miR-152 and BMP9 was assessed by qRT-PCR and dual luciferase activity assay. The effects of BMP9 on cell proliferation and osteogenic differentiation were determined in BMSCs after transfection with pEX-BMP9 and sh-BMP9. The key components in PI3K/AKT and Wnt/β-catenin pathways were analyzed by Western blot.

RESULTS:

APS promoted proliferation and differentiation of BMSCs by increasing viable cells, up-regulating CyclinD1, down-regulating p21, and increasing expressions of Runx2, OCN, OPN, and Col-1. miR-152 was down-regulated by APS and miR-152 suppression exhibited the similar promoting effects on BMSCs, whereas miR-152 overexpression inhibited proliferation and differentiation of BMSCs. BMP9 was a direct target of miR-152 and was involved in mediating the function of miR-152 in BMSCs. BMP9 up-regulation enhanced proliferation and differentiation of BMSCs. BMP9 was observed to activate PI3K/AKT and Wnt/β-catenin pathways in BMSCs.

CONCLUSION:

These results demonstrated that APS promoted proliferation and osteogenic differentiation of BMSCs by down-regulating miR-152 and further up-regulating BMP9 and activating PI3K/AKT and Wnt/β-catenin pathways.

KEYWORDS:

Astragalus polysaccharide; BMP9; Bone mesenchymal stem cell; microRNA-152

PMID:
31071509
DOI:
10.1016/j.biopha.2019.108927
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