期刊
BIOMATERIALS
卷 177, 期 -, 页码 1-13出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2018.05.035
关键词
pDNA; shRNA; Multi-lineage; MSC; Gene regulation nanoparticles
资金
- National Research Foundation of Korea (NRF) - Korean Government [NRF-2017R1A2A1A05001264, NRF-2017M3A9C6061360, NRF-2015R1A1A3A04000928, NRF- 2017M3A9B4031169]
- National Research Foundation of Korea [2017M3A9B4031169, 2017M3A9C6061360] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Overexpression and knockdown of specific proteins can control stem cell differentiation for therapeutic purposes. In this study, we fabricated RUNX2, SOX9, and C/EBP alpha plasmid DNAs (pDNAs) and ATF4-targeting shRNA (shATF4) to induce osteogenesis, chondrogenesis, and adipogenesis of human mesenchymal stem cells (hMSCs). The pDNAs and shATF4 were complexed with TRITC-gene regulation nanoparticles (GRN). Osteogenesis-related gene expression was reduced at early (12 h) and late (36 h) time points after co-delivery of shATF4 and SOX9 or C/EBP alpha pDNA, respectively, and osteogenesis was inhibited in these hMSCs. By contrast, osteogenesis-related genes were highly expressed upon co-delivery of RUNX2 and ATF4 pDNAs. DEX in GRN enhanced chondrogenic differentiation. Expression of osteogenesis-, chondrogenesis-, and adipogenesis-related genes was higher in hMSCs transfected with NPs complexed with RUNX2 and ATF4 pDNAs, shATF4 and SOX9 pDNA, and shATF4 and C/EBP alpha pDNA for 72 h than in control hMSCs, respectively. Moreover, delivery of these NPs also increased expression of osteogenesis-, chondrogenesis-, and adipogenesis-related proteins. These alterations in expression led to morphological changes, indicating that hMSCs differentiated into osteoblasts, chondrocytes, and adipose cells. (C) 2018 Elsevier Ltd. All rights reserved.
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