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.
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.
Authors: G Brunetti; S Colucci; P Pignataro; M Coricciati; G Mori; N Cirulli; A Zallone; F R Grassi; M Grano Journal: J Periodontol Date: 2005-10 Impact factor: 6.993
Authors: S Papa; C Bubici; F Zazzeroni; C G Pham; C Kuntzen; J R Knabb; K Dean; G Franzoso Journal: Cell Death Differ Date: 2006-05 Impact factor: 15.828
Authors: Cristina Vincent; David M Findlay; Katie J Welldon; Asiri R Wijenayaka; Timothy S Zheng; David R Haynes; Nicola L Fazzalari; Andreas Evdokiou; Gerald J Atkins Journal: J Bone Miner Res Date: 2009-08 Impact factor: 6.741