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  • Title: Dose-specific effects of tumor necrosis factor alpha on osteogenic differentiation of mesenchymal stem cells.
    Author: Huang H, Zhao N, Xu X, Xu Y, Li S, Zhang J, Yang P.
    Journal: Cell Prolif; 2011 Oct; 44(5):420-7. PubMed ID: 21951285.
    Abstract:
    OBJECTIVES: To investigate tumor necrosis factor alpha (TNF-α)-induced changes in osteogenic differentiation from mesenchymal stem cells (MSCs). MATERIALS AND METHODS: Blockade of nuclear factor-κB (NF-κB) was achieved in ST2 murine MSCs via overexpression of the NF-κB inhibitor, IκBα. Osteogenic differentiation was induced in IκBα-overexpressing ST2 cells and normal ST2 cells when these cells were treated with TNF-α at various concentrations. Expression levels of bone marker genes were determined using real time RT-PCR and ALP activity assay. In vitro mineralization was performed to determine long-term exposure to TNF-α on mineral nodule formation. MTT assay was used to determine the changes in cell proliferation/survival. RESULTS: Levels of Runx2, Osx, OC and ALP were up-regulated in cell cultures treated with TNF-α at lower concentrations, while down-regulated in cell cultures treated with TNF-α at higher concentrations. Blockade of NF-κB signaling reversed the inhibitory effect observed in cell cultures treated with TNF-α at higher concentrations, but showed no effect on cell cultures treated with TNF-α at lower concentrations. In contrast, long-term treatment of TNF-α at all concentrations induced inhibitory effects on in vitro mineral nodule formation. MTT assay showed that TNF-α inhibits proliferation/survival of mesenchymal stem cells when the NF-κB signaling pathway is blocked. CONCLUSIONS: The binding of TNF-α to its receptors results in the activation of multiple signaling pathways, which actively interact with each other to regulate the differentiation, proliferation, survival and apoptosis of MSCs.
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