Apoptosis Repressor with Caspase Domain (ARC) Promotes Bone Regeneration of Bone Marrow Derived Mesenchymal Stem Cells via Activating Fgf-2/PI3K/Akt Signaling release_4klr3decwbhhlov3uz2ehnvqmi

Abstract

<jats:title>Abstract</jats:title> <jats:italic>Objectives:</jats:italic><jats:italic>This study aims to investigate whether ARC could promote survival and enhance osteogenic differentiation of bone marrow derived mesenchymal stem cells (BMSCs).</jats:italic><jats:italic>Material and methods:</jats:italic><jats:italic>Lentivirus transfection method was used to establish ARC overexpressed BMSCs. 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 immunofluoresence staining, ALP, ARS assay and RT-PCR analysis. Cells were seeded into CPC scaffolds, then inserted into subcutaneous of nude mice and the defect area of rat's calvarium. Histological analysis was conducted to evaluate in vivo cell apoptosis and new bone formation ability of ARC overexpressed BMSCs. RNA-seq method was used to detect the possible mechanism of the effect of ARC on BMSCs. </jats:italic><jats:italic>Results:</jats:italic><jats:italic>ARC can promote BMSCs proliferation and inhibit its cell apoptosis. ARC can enhance BMSCs osteogenic differentiation in vitro. In vivo study revealed ARC can inhibit BMSCs' apoptosis and increase its new bone formation ability. ARC regulates BMSCs mainly by activating Fgf-2/PI3K/Akt pathway.</jats:italic><jats:italic>Conclusions: </jats:italic><jats:italic>The present study suggested that ARC is a powerful agent to promote bone regeneration of BMSCs and provides a promising method for bone tissue engineering.</jats:italic>
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