TGF-β1 promotes the osteoinduction of human osteoblasts via the PI3K/AKT/mTOR/S6K1 signalling pathway

被引:85
作者
Zhang, Zhaodong [1 ]
Zhang, Xiuzhi [1 ,2 ]
Zhao, Dewei [1 ]
Liu, Baoyi [1 ]
Wang, Benjie [1 ]
Yu, Weiting [1 ]
Li, Junlei [1 ,2 ]
Yu, Xiaobing [1 ,2 ]
Cao, Fang [3 ]
Zheng, Guoshuang [1 ]
Zhang, Yao [1 ]
Liu, Yupeng [1 ]
机构
[1] Dalian Univ, Affiliated Zhongshan Hosp, Dept Orthopaed, 6 Jiefang St, Dalian 116001, Liaoning, Peoples R China
[2] Chinese Acad Sci, Inst Met Res, Dept Special Mat & Devices, Shenyang 110016, Liaoning, Peoples R China
[3] Dalian Univ Technol, Fac Elect Informat & Elect Engn, Dept Biomed Engn, Dalian 116024, Liaoning, Peoples R China
基金
中国博士后科学基金;
关键词
transforming growth factor 1; osteoinduction; phosphatidylinositol; 3-kinase; protein kinase B; mammalian target of rapamycin; S6; kinase; 1; GROWTH-FACTOR-BETA; MESENCHYMAL STEM-CELLS; TGF-BETA; BONE-FORMATION; IN-VITRO; DIFFERENTIATION; EXPRESSION; ENHANCE; CANCER; OSTEOCLASTS;
D O I
10.3892/mmr.2019.10051
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Transforming growth factor 1 (TGF-1) 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 TGF-1 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 3-kinase/protein kinase B/mammalian target of rapamycin/S6 kinase 1 (PI3K/AKT/mTOR/S6K1) signalling pathway in the effects of TGF-1 on osteoblasts was investigated. It was demonstrated using Cell Counting Kit-8 and flow cytometry assays that the proliferation of human osteoblasts was promoted by 1 ng/ml TGF-1. In addition, alkaline phosphatase activity, Alizarin red staining, scratch-wound and Transwell assays were conducted. It was revealed that osteogenesis and the migration of cells were regulated by TGF-1 via the upregulation of osteogenic and migration-associated genes. Alterations in the expression of osteogenesis- and migration-associated genes were evaluated following pre-treatment with a PI3K/AKT inhibitor (LY294002) and an mTOR/S6K1 inhibitor (rapamycin), with or without TGF-1. The results indicated that TGF-1 affected the osteogenesis and mineralisation of osteoblasts via the PI3K/AKT signalling pathway. Furthermore, TGF-1 exhibited effects on mTOR/S6K1 downstream of PI3K/AKT. The present study demonstrated that TGF-1 promoted the proliferation, differentiation and migration of human hFOB1.19 osteoblasts, and revealed that TGF-1 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.
引用
收藏
页码:3505 / 3518
页数:14
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