Knockdown of SIRT7 enhances the osteogenic differentiation of human bone marrow mesenchymal stem cells partly via activation of the Wnt/β-catenin signaling pathway

被引:65
作者
Chen, Erman E. M. [1 ,2 ]
Zhang, Wei [1 ,2 ]
Ye, Chenyi C. Y. [1 ,2 ]
Gao, Xiang [1 ]
Jiang, Liangjun L. J. [1 ]
Zhao, Tengfei T. F. [1 ]
Pan, Zhijun Z. J. [1 ,2 ]
Xue, Deting D. T. [1 ,2 ]
机构
[1] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Orthoped, 88 Jiefang Rd, Hangzhou 310000, Zhejiang, Peoples R China
[2] Zhejiang Univ, Orthoped Res Inst, Hangzhou 310000, Zhejiang, Peoples R China
基金
中国国家自然科学基金;
关键词
BETA-CATENIN; TRANSCRIPTION FACTORS; WNT; EXPRESSION; DICKKOPF-1; APOPTOSIS; PROTEINS; SIRTUINS; RECEPTOR; GROWTH;
D O I
10.1038/cddis.2017.429
中图分类号
Q2 [细胞生物学];
学科分类号
071013 [干细胞生物学];
摘要
Sirtuin 7 (SIRT7) is a NAD(+)-dependent deacetylase in the sirtuin family. In a previous study, human bone marrow mesenchymal stem cells (hBMSCs) with reduced SIRT7 activity were developed to evaluate the effect of SIRT7 on osteogenesis. SIRT7 knockdown significantly enhanced osteoblast-specific gene expression, alkaline phosphatase activity, and mineral deposition in vitro. Additionally, SIRT7 knockdown upregulated beta-catenin. The enhanced osteogenesis due to SIRT7 knockdown was partially rescued by a Wnt/beta-catenin inhibitor. Furthermore, SIRT7 knockdown hBMSCs combined with a chitosan scaffold significantly promoted bone formation in a rat tibial defect model, as determined by imaging and histological examinations. These findings suggest that SIRT7 has an essential role in osteogenic differentiation of hBMSCs, partly by activation of the Wnt/beta-catenin signaling pathway.
引用
收藏
页码:e3042 / e3042
页数:11
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