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沉默 SIRT7 部分通过激活 Wnt/β-连环蛋白信号通路增强人骨髓间充质干细胞的成骨分化。

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

机构信息

Department of Orthopedics, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310000, People's Republic of China.

Orthopedics Research Institute of Zhejiang University, Hangzhou 310000, People's Republic of China.

出版信息

Cell Death Dis. 2017 Sep 7;8(9):e3042. doi: 10.1038/cddis.2017.429.

Abstract

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 β-catenin. The enhanced osteogenesis due to SIRT7 knockdown was partially rescued by a Wnt/β-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/β-catenin signaling pathway.

摘要

Sirtuin 7(SIRT7)是 sirtuin 家族中一种依赖 NAD 的去乙酰化酶。在之前的一项研究中,开发了 SIRT7 活性降低的人骨髓间充质干细胞(hBMSCs),以评估 SIRT7 对成骨的影响。SIRT7 敲低显著增强了体外成骨细胞特异性基因表达、碱性磷酸酶活性和矿化沉积。此外,SIRT7 敲低还上调了 β-catenin。Wnt/β-catenin 抑制剂部分挽救了由于 SIRT7 敲低导致的增强的成骨作用。此外,SIRT7 敲低 hBMSCs 与壳聚糖支架结合,通过成像和组织学检查,在大鼠胫骨缺损模型中显著促进了骨形成。这些发现表明 SIRT7 在 hBMSCs 的成骨分化中起着至关重要的作用,部分是通过激活 Wnt/β-catenin 信号通路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76a2/5636975/29128f804682/cddis2017429f1.jpg

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