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

• Published in: Cell death & disease Vol. 8; no. 9; p. e3042
• Main Authors: Chen, Erman E M, Zhang, Wei, Ye, Chenyi C Y, Gao, Xiang, Jiang, Liangjun L J, Zhao, Tengfei T F, Pan, Zhijun Z J, Xue, Deting D T
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 07.09.2017
• Subjects: Alkaline Phosphatase - genetics; Alkaline Phosphatase - metabolism; Animals; beta Catenin - genetics; beta Catenin - metabolism; Bone Marrow Cells - cytology; Bone Marrow Cells - drug effects; Bone Marrow Cells - metabolism; Bone Regeneration - drug effects; Bone Regeneration - genetics; Cell Adhesion - drug effects; Cell Differentiation - drug effects; Cells, Cultured; Chitosan - chemistry; Collagen Type I - genetics; Collagen Type I - metabolism; Core Binding Factor Alpha 1 Subunit - genetics; Core Binding Factor Alpha 1 Subunit - metabolism; Gene Expression Regulation; Genetic Vectors - chemistry; Genetic Vectors - metabolism; Humans; Intercellular Signaling Peptides and Proteins - genetics; Intercellular Signaling Peptides and Proteins - metabolism; Intercellular Signaling Peptides and Proteins - pharmacology; Lentivirus - genetics; Lentivirus - metabolism; Male; Mesenchymal Stem Cell Transplantation; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - drug effects; Mesenchymal Stromal Cells - metabolism; Original; Osteoblasts - cytology; Osteoblasts - drug effects; Osteoblasts - metabolism; Rats; Rats, Sprague-Dawley; Signal Transduction; Sirtuins - antagonists & inhibitors; Sirtuins - genetics; Sirtuins - metabolism; Tibia - drug effects; Tibia - injuries; Tibia - metabolism; Tibia - pathology; Tissue Scaffolds
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/cddis.2017.429

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.