Abstract
Abstract
Objectives
This study aims to investigate whether apoptosis repressor with caspase recruitment domain (ARC) could promote survival and enhance osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs).
Materials and methods
The lentivirus transfection method was used to establish ARC-overexpressing BMSCs. The CCK-8 method was used to detect cell proliferation. The BD Pharmingen™ APC Annexin V Apoptosis Detection kit was used to detect cell apoptosis. The osteogenic capacity was investigated by OCN immunofluorescence staining, ALP analysis, ARS assays, and RT-PCR analysis. Cells were seeded into calcium phosphate cement (CPC) scaffolds and then inserted subcutaneously into nude mice and the defect area of the rat calvarium. Histological analysis was conducted to evaluate the in vivo cell apoptosis and new bone formation of the ARC-overexpressing BMSCs. RNA-seq was used to detect the possible mechanism of the effect of ARC on BMSCs.
Results
ARC promoted BMSC proliferation and inhibited cell apoptosis. ARC enhanced BMSC osteogenic differentiation in vitro. An in vivo study revealed that ARC can inhibit BMSC apoptosis and increase new bone formation. ARC regulates BMSCs mainly by activating the Fgf-2/PI3K/Akt pathway.
Conclusions
The present study suggests that ARC is a powerful agent for promoting bone regeneration of BMSCs and provides a promising method for bone tissue engineering.
Funder
Shanghai Sailing Program
Young Scientists Fund
Young Physician Innovation Team Project from Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine
Publisher
Springer Science and Business Media LLC
Subject
Cell Biology,Biochemistry, Genetics and Molecular Biology (miscellaneous),Molecular Medicine,Medicine (miscellaneous)
Cited by
7 articles.
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