TGFß1 promotes the osteoinduction of human osteoblasts via the PI3K/AKT/mTOR/S6K1 signalling pathway.
Mol Med Rep
; 19(5): 3505-3518, 2019 May.
Article
em En
| MEDLINE
| ID: mdl-30896852
ABSTRACT
Transforming growth factor ß1 (TGFß1) has been suggested to be a candidate cytokine in the field of bone tissue engineering. Cytokines serve important roles in tissue engineering, particularly in the repair of bone damage; however, the underlying molecular mechanisms remain unclear. In the present study, the effects of TGFß1 on the osteogenesis and motility of hFOB1.19 human osteoblasts were demonstrated via the phenotype and gene expression of cells. Additionally, the role of the phosphatidylinositol 3kinase/protein kinase B/mammalian target of rapamycin/S6 kinase 1 (PI3K/AKT/mTOR/S6K1) signalling pathway in the effects of TGFß1 on osteoblasts was investigated. It was demonstrated using Cell Counting Kit8 and flow cytometry assays that the proliferation of human osteoblasts was promoted by 1 ng/ml TGFß1. In addition, alkaline phosphatase activity, Alizarin red staining, scratchwound and Transwell assays were conducted. It was revealed that osteogenesis and the migration of cells were regulated by TGFß1 via the upregulation of osteogenic and migrationassociated genes. Alterations in the expression of osteogenesis and migrationassociated genes were evaluated following pretreatment with a PI3K/AKT inhibitor (LY294002) and an mTOR/S6K1 inhibitor (rapamycin), with or without TGFß1. The results indicated that TGFß1 affected the osteogenesis and mineralisation of osteoblasts via the PI3K/AKT signalling pathway. Furthermore, TGFß1 exhibited effects on mTOR/S6K1 downstream of PI3K/AKT. The present study demonstrated that TGFß1 promoted the proliferation, differentiation and migration of human hFOB1.19 osteoblasts, and revealed that TGFß1 affected the biological activity of osteoblasts via the PI3K/AKT/mTOR/S6K1 signalling pathway. Our findings may provide novel insight to aid the development of bone tissue engineering methods for the treatment of bone injury.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Osteoblastos
/
Transdução de Sinais
/
Fosfatidilinositol 3-Quinases
/
Proteínas Quinases S6 Ribossômicas 70-kDa
/
Proteínas Proto-Oncogênicas c-akt
/
Fator de Crescimento Transformador beta1
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article