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.
Highlights
Bone marrow stem cells (BMSCs) possess self-renewal capabilities and the potential to differentiate into a variety of cell types, including osteoblasts, chondrocytes, and adipocytes.[1]
We investigated the expression of SIRT7 in human BMSCs and its effect on the osteogenic differentiation of hBMSCs
By assessing the expression levels of specific osteogenic markers and calcium deposition, we revealed that SIRT7 knockdown enhances osteogenic differentiation of hBMSCs partly via the Wnt/β-catenin signaling pathway in vitro
Summary
Bone marrow stem cells (BMSCs) possess self-renewal capabilities and the potential to differentiate into a variety of cell types, including osteoblasts, chondrocytes, and adipocytes.[1]. Little is known about the role of SIRT7 in the osteogenesis of MSCs. Wnt/β-catenin signaling is a crucial regulator of MSCs that has important roles in osteogenic differentiation.[14,15] The canonical Wnt signaling pathway is activated upon Wnt binding to frizzled receptors[16] and LRP co-receptor at the cell membrane,[17,18] causing inhibition of glycogen synthase kinase-3β (GSK3β) and stabilizing cytoplasmic β-catenin.[15] Via activation of Wnt, β-catenin accumulates in the cytosol and translocates to the nucleus where it promotes T-cell factor/ lymphoid enhancing factor-1-mediated transcription,[19,20] thereby affecting target gene transcription. We used a rat tibial defect model transplanted with SIRT7 knockdown hBMSCs, combined with the use of a chitosan scaffold, and found that SIRT7 knockdown promoted healing of bone defects in vivo
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
