Magnetic iron oxide nanoparticles accelerate osteogenic differentiation of mesenchymal stem cells via modulation of long noncoding RNA INZEB2  

作　　者：Qiwei Wang Bo Chen Fang Ma Shikang Lin Meng Cao Yan Li Ning Gu 

机构地区：[1]State Key Laboratory ofBioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Sciences & Medical Engineering, Southeast University, Nanjing 210096, China [2]Collaborative Innovation Center of Suzhou Nano Science and Technology, Suzhou 215123, China [3]Key Laboratory of Developmental Genes and Human Diseases in Ministry of Education, Institute of Life Sciences, Southeast University, Nanjing 210096, China [4]SignalwayAntibody LLC, College Park, MD 20740, USA

出　　处：《Nano Research》2017年第2期626-642,共17页纳米研究（英文版）

摘　　要：Nanomaterials are increasingly used for biomedical applications; thus, it is important to understand their biological effects. Previous studies suggested that magnetic iron oxide nanoparticles （IONPs） have tissue-repairing effects. In the present study, we explored cellular effects of IONPs in mesenchymal stem cells （MSCs） and identified the underlying molecular mechanisms. The results showed that our as-prepared IONPs were structurally stable in MSCs and promoted osteogenic differentiation of MSCs as whole particles. Moreover, at the molecular level, we compared the gene expression of MSCs with or without IONP exposure and showed that IONPs upregulated long noncoding RNA INZEB2, which is indispensable for maintaining osteogenesis by MSCs. Furthermore, overexpression of INZEB2 downregulated ZEB2, a factor necessary to repress BMP/Smad- dependent osteogenic transcription. We also demonstrated that the essential role of INZEB2 in osteogenic differentiation was ZEB2-dependent. In summary, we elucidated the molecular basis of IONPs＇ effects on MSCs; these findings may serve as a meaningful theoretical foundation for applications of stem cells to regenerative medicine.Nanomaterials are increasingly used for biomedical applications; thus, it is important to understand their biological effects. Previous studies suggested that magnetic iron oxide nanoparticles （IONPs） have tissue-repairing effects. In the present study, we explored cellular effects of IONPs in mesenchymal stem cells （MSCs） and identified the underlying molecular mechanisms. The results showed that our as-prepared IONPs were structurally stable in MSCs and promoted osteogenic differentiation of MSCs as whole particles. Moreover, at the molecular level, we compared the gene expression of MSCs with or without IONP exposure and showed that IONPs upregulated long noncoding RNA INZEB2, which is indispensable for maintaining osteogenesis by MSCs. Furthermore, overexpression of INZEB2 downregulated ZEB2, a factor necessary to repress BMP/Smad- dependent osteogenic transcription. We also demonstrated that the essential role of INZEB2 in osteogenic differentiation was ZEB2-dependent. In summary, we elucidated the molecular basis of IONPs＇ effects on MSCs; these findings may serve as a meaningful theoretical foundation for applications of stem cells to regenerative medicine.

关 键 词：iron oxide nanoparticle mesenchymal stem cell osteogenic differentiation long noncoding RNA magnetogenetics nano-magnetic bioeffects 

分 类 号：O[理学]