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Dose-specific effects of tumor necrosis factor alpha on osteogenic differentiation of mesenchymal stem cells

2011; Wiley; Volume: 44; Issue: 5 Linguagem: Inglês

10.1111/j.1365-2184.2011.00769.x

1365-2184

Haiyun Huang, Ning Zhao, Xin Xu, Yingjie Xu, Shuang Li, J. Zhang, Pishan Yang,

NF-κB Signaling Pathways

Objectives: To investigate tumor necrosis factor alpha (TNF-a)-induced changes in osteogenic differentiation from mesenchymal stem cells (MSCs).Materials and methods: Blockade of nuclear factor-jB (NF-jB) was achieved in ST2 murine MSCs via overexpression of the NF-jB inhibitor, IjBa.Osteogenic differentiation was induced in IjBa-overexpressing ST2 cells and normal ST2 cells when these cells were treated with TNF-a 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-a 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-a at lower concentrations, while down-regulated in cell cultures treated with TNF-a at higher concentrations.Blockade of NF-jB signaling reversed the inhibitory effect observed in cell cultures treated with TNF-a at higher concentrations, but showed no effect on cell cultures treated with TNF-a at lower concentrations.In contrast, long-term treatment of TNF-a at all concentrations induced inhibitory effects on in vitro mineral nodule formation.MTT assay showed that TNF-a inhibits proliferation ⁄ survival of mesenchymal stem cells when the NF-jB signaling pathway is blocked. Conclusions:The binding of TNF-a 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.