miR-193a inhibits osteogenic differentiation of bone marrow-derived stroma cell via targeting HMGB1.
Biochem Biophys Res Commun
; 503(2): 536-543, 2018 09 05.
Article
em En
| MEDLINE
| ID: mdl-29787753
ABSTRACT
BACKGROUND:
miR-193a has been shown to be involved in a variety of biological processes, including cell proliferation, differentiation, and apoptosis. However, little is known about how miR-193a regulates osteogenic differentiation.METHODS:
We employed RT-qPCR to determine the level of miR-193a and mRNA level of HMGB1 and osteoblast-specific markers (Runx2, ALP, OSX, OCN). Besides, westernblot was used to probe protein level of phosphorylated MAPK family members and ß-catenin. Bioinformatic analysis was used to predict the putative binding sequence of miR-193a to the 3'-UTR of HMGB1 and we confirmed this result by dual luciferase reporter assay. Alizarin red staining assay (ARS) and alkaline phosphatase activity (ALP) were performed to detect osteogenic differentiation.RESULTS:
miR-193a was downregulated in OM (osteogenic medium)induced hBMSC. More interestingly, we found that miR-193a mimic attenuated matrix mineralization and alkaline phosphatase activity, whereas miR-193a inhibitor exerted the opposite phenotypes. Mechanistically, we observed that miR-193a played an inhibitory role in expression of osteoblast-specific markers and activation of MAPK and Wnt signaling pathways. Bioinformatic analysis and dual luciferase assay demonstrated that miR-193a directly targeted 3'-UTR of HMGB1. Furthermore, we overexpressed HMGB1 in miR-193a overexpressed hBMSC to establish that HMGB1 acted as downstream target of miR-193a-inhibited osteogenic differentiation.CONCLUSIONS:
Here, we reveal miR-193a plays a suppressive role in osteogenic differentiation of hBMSC via targeting HMGB1. These findings provide a novel mechanism underlying osteogenic differentiation and offer therapeutical strategy for bone formation.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Osteoblastos
/
Osteogênese
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Proteína HMGB1
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MicroRNAs
/
Células-Tronco Mesenquimais
Tipo de estudo:
Prognostic_studies
Limite:
Humans
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Male
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article