Silver Nanoparticles Promote the Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells by Modulating the O-GlcNAcylation of RUNX1

Abstract

Human BMSCs are multifunctional progenitor cells that can transferred into different functional cells. Silver nanoparticles (AgNPs) has been demonstrated to modulate the osteogenesis of stem cells. However, effects of AgNPs on hBMSC functions and their potential modulatory mechanism remain elusive. Our study aimed to thoroughly analyze the role of AgNPs in mediating hBMSCs osteogenic differentiation. In this study, we found that hBMSCs viability as well as osteogenic differentiation were significantly promoted when treated with 4 μg/ml AgNPs. Aberrant O-GlcNAcylation can affect multiple biological processes of human eukaryotes, including osteogenic differentiation of hBMSCs. Here, we demonstrated that AgNPs could increase the O-GlcNAcylation level to exert their functions. Further mechanistic investigation revealed that AgNPs enhanced the protein level of runt-related transcription Factor 1 (RUNX1) by O-glycosylating it at the T219 site to stabilize the RUNX1 protein. Finally, we determined that silencing RUNX1 abrogated AgNPs function on the viability and hBMSCs osteogenic differentiation. In conclusion, this study reported a novel mechanism by which AgNPs promoted hBMSCs osteogenic differentiation.