miR29b promotes the osteogenic differentiation of mesenchymal stem cells derived from human adipose tissue via the PTEN/AKT/ßcatenin signaling pathway.
Int J Mol Med
; 46(2): 709-717, 2020 Aug.
Article
em En
| MEDLINE
| ID: mdl-32468003
ABSTRACT
Accumulating evidence has documented that microRNAs (miRNAs or miRs) function as important posttranscriptional regulators of the differentiation of mesenchymal stem cells (MSCs), including human adiposederived mesenchymal stem cells (hADSCs); however, their roles in hADSC osteogenic differentiation require further investigation. The present study aimed to investigate the role of miRNAs in the osteogenic differentiation of hADSCs and to elucidate the underlying molecular mechanisms. Using an miRNA microarray, it was found that 24 miRNAs were upregulated and 14 miRNAs were downregulated compared with the undifferentiated cells, and miR29b3p (miR29b) was selected for further experiments. Functional experiments revealed that the upregulation of miR29b by agomir29b significantly enhanced alkaline phosphatase (ALP) activity and the mineralization of extracellular matrix (ECM), and led to an increase in the mRNA and protein levels of osteogenic marker genes, including runtrelated transcription factor 2 (Runx2), osteopontin (OPN), osteocalcin (OCN) and bone sialoprotein (BSP), whereas the knockdown of miR29b suppressed these processes. In addition, phosphatase and tensin homolog (PTEN), a negative regulator of the AKT/ßcatenin pathway, was identified as a direct target of miR29b in the hADSCs. Moreover, it was observed that the overexpression of miR29b activated the AKT/ßcatenin signaling pathway by inhibiting PTEN expression in the hADSCs. Most importantly, it was also found that the overexpression of PTEN reversed the promoting effects of miR29b on osteogenic differentiation. On the whole, these findings suggest that miR29b promotes the osteogenic differentiation of hADSCs by modulating the PTEN/AKT/ßcatenin signaling pathway. Thus, this miRNA may be a promising target for the active modulation of hADSCderived osteogenesis.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Osteogênese
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MicroRNAs
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PTEN Fosfo-Hidrolase
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Proteínas Proto-Oncogênicas c-akt
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Beta Catenina
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Int J Mol Med
Assunto da revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Ano de publicação:
2020
Tipo de documento:
Article