Ginkgo biloba extract promotes osteogenic differentiation of human bone marrow mesenchymal stem cells in a pathway involving Wnt/ß-catenin signaling.
Pharmacol Res
; 97: 70-8, 2015 Jul.
Article
em En
| MEDLINE
| ID: mdl-25917209
ABSTRACT
Human bone marrow derived mesenchymal stem cells (BM-MSCs) are a novel cell source used in stem cell therapy to treat bone diseases owing to their high potential to differentiate into osteoblasts. Effective induction of osteogenic differentiation from human BM-MSCs is critical to fulfill their therapeutic potential. In this study, Ginkgo biloba extract (GBE), a traditional herbal medicine, was used to stimulate the proliferation and osteogenic differentiation of human BM-MSCs. The present study revealed that GBE improved the proliferation and osteogenesis of human BM-MSCs in a dose-dependent manner in the range 25-75 mg/l, as indicated by alkaline phosphatase (ALP) activity and calcium content. However, such effect was decreased or inhibited at 100mg/l or higher. The dose-dependent improvement in osteogenesis of human BM-MSCs by GBE was further confirmed by the dose-dependent upregulation of marker genes, osteopontin (OPN) and Collagen I. The increased osteoprotegerin (OPG) expression and minimal expression of receptor activator of nuclear factor-κB ligand (RANKL) suggested that GBE also inhibited osteoclastogenesis of human BM-MSCs. Further mechanistic study demonstrated that the transcriptional levels of bone morphogenetic protein 4 (BMP4) and runt-related transcription factor 2 (RUNX2) in the BMP signaling, ß-catenin and Cyclin D1 in the Wnt/ß-catenin signaling, increased significantly during GBE-promoted osteogenesis. Meanwhile, loss-of-function assay with the signaling inhibitor(s) confirmed that the BMP and Wnt/ß-catenin signaling pathways were indispensable during the GBE-promoted osteogenesis, suggesting that GBE improved osteogenesis via upregulation of the BMP and Wnt/ß-catenin signaling. The present study proposed GBE to be used to upregulate the osteogenic differentiation of human BM-MSCs for new bone formation in BM-MSC-based cell therapy, which could provide an attractive and promising treatment for bone disorders.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
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Tratamento
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Transplante_de_medula_ossea
Base de dados:
MEDLINE
Assunto principal:
Osteogênese
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Células da Medula Óssea
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Extratos Vegetais
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Ginkgo biloba
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Proteínas Wnt
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Cateninas
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Células-Tronco Mesenquimais
Limite:
Humans
Idioma:
En
Revista:
Pharmacol Res
Assunto da revista:
FARMACOLOGIA
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
China