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      Silver nanoparticle based coatings enhance adipogenesis compared to osteogenesis in human mesenchymal stem cells through oxidative stress

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          Abstract

          Silver nanoparticle based coatings preserve the osteogenesis capacity while promoting the adipogenesis of human mesenchymal stem cells through oxidative stress.

          Abstract

          Silver nanoparticle (AgNP) based antibacterial surfaces were fabricated using plasma polymerization technology and their effects on differentiation of human bone-marrow derived mesenchymal stem cells (hMSCs) were investigated in this study. The results showed that AgNP coated surfaces do not affect the initial adhesion, spreading and proliferation of hMSCs. Furthermore, the silver coated surface promoted adipogenic differentiation of hMSCs as demonstrated by more accumulation of lipid droplets and upregulation of adipogenesis-related genes such as peroxisome proliferator activated receptor gamma (PPARγ), adipocyte determination and differentiation factor (ADD1) and CCAAT/enhancer binding protein alpha (C/EBPα). In addition, silver incorporation activated the expression of antioxidant enzymes as a consequence of the accumulation of intracellular reactive oxygen species (ROS) in adipogenic induced cells, which was correlated with the enhanced adipogenic capacity of hMSCs. ROS generation was enhanced due to silver ion release and consequently reduced osteogenesis at the early stage after 7 days of osteogenic induction as a result of reducing alkaline phosphatase (ALP) activity. However, the differentiation and mineralization capacity of osteoblasts were restored after 14 days of osteogenic induction, which indicated that adipogenesis favors intracellular ROS accumulation mediated by silver coatings compared to osteogenesis. None of the osteogenic related genes was affected by ROS mediated by AgNP dissolution. The findings in this work are instructive for the use of silver as an antibacterial agent in the areas of tissue engineering, stem cell therapies and implantable biomedical devices.

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          Most cited references39

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          The control of human mesenchymal cell differentiation using nanoscale symmetry and disorder.

          A key tenet of bone tissue engineering is the development of scaffold materials that can stimulate stem cell differentiation in the absence of chemical treatment to become osteoblasts without compromising material properties. At present, conventional implant materials fail owing to encapsulation by soft tissue, rather than direct bone bonding. Here, we demonstrate the use of nanoscale disorder to stimulate human mesenchymal stem cells (MSCs) to produce bone mineral in vitro, in the absence of osteogenic supplements. This approach has similar efficiency to that of cells cultured with osteogenic media. In addition, the current studies show that topographically treated MSCs have a distinct differentiation profile compared with those treated with osteogenic media, which has implications for cell therapies.
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            Silver as antibacterial agent: ion, nanoparticle, and metal.

            The antibacterial action of silver is utilized in numerous consumer products and medical devices. Metallic silver, silver salts, and also silver nanoparticles are used for this purpose. The state of research on the effect of silver on bacteria, cells, and higher organisms is summarized. It can be concluded that the therapeutic window for silver is narrower than often assumed. However, the risks for humans and the environment are probably limited. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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              Glutathione peroxidase 4 senses and translates oxidative stress into 12/15-lipoxygenase dependent- and AIF-mediated cell death.

              Oxidative stress in conjunction with glutathione depletion has been linked with various acute and chronic degenerative disorders, yet the molecular mechanisms have remained unclear. In contrast to the belief that oxygen radicals are detrimental to cells and tissues by unspecific oxidation of essential biomolecules, we now demonstrate that oxidative stress is sensed and transduced by glutathione peroxidase 4 (GPx4) into a-yet-unrecognized cell-death pathway. Inducible GPx4 inactivation in mice and cells revealed 12/15-lipoxygenase-derived lipid peroxidation as specific downstream event, triggering apoptosis-inducing factor (AIF)-mediated cell death. Cell death could be entirely prevented either by alpha-tocopherol (alpha-Toc), 12/15-lipoxygenase inhibitors, or siRNA-mediated AIF silencing. Accordingly, 12/15-lipoxygenase-deficient cells were highly resistant to glutathione depletion. Neuron-specific GPx4 depletion caused neurodegeneration in vivo and ex vivo, highlighting the importance of this pathway in neuronal cells. Since oxidative stress is common in the etiology of many human disorders, the identified pathway reveals promising targets for future therapies.
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                Author and article information

                Journal
                JMCBDV
                Journal of Materials Chemistry B
                J. Mater. Chem. B
                Royal Society of Chemistry (RSC)
                2050-750X
                2050-7518
                2016
                2016
                : 4
                : 8
                : 1466-1479
                Affiliations
                [1 ]State Key Laboratory of New Ceramics and Fine Processing
                [2 ]School of Materials Science and Engineering
                [3 ]Tsinghua University
                [4 ]Beijing 100084
                [5 ]China
                [6 ]Mawson Institute
                [7 ]University of South Australia
                [8 ]Mawson Lakes
                [9 ]Australia
                [10 ]School of Advanced Manufacturing
                Article
                10.1039/C5TB02482J
                c6530916-6faa-475d-856b-2cf2e824a789
                © 2016
                History

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