RRC ID 18598
著者 Huang H, Zhao N, Xu X, Xu Y, Li S, Zhang J, Yang P.
タイトル Dose-specific effects of tumor necrosis factor alpha on osteogenic differentiation of mesenchymal stem cells.
ジャーナル Cell Prolif
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.
巻・号 44(5)
ページ 420-7
公開日 2011-10-1
DOI 10.1111/j.1365-2184.2011.00769.x
PMID 21951285
PMC PMC6495272
MeSH Alkaline Phosphatase / metabolism Animals Apoptosis / drug effects Base Sequence Calcification, Physiologic / drug effects Cell Differentiation / drug effects Cell Line Cell Proliferation / drug effects Cell Survival / drug effects Core Binding Factor Alpha 1 Subunit / metabolism DNA Primers / genetics Dose-Response Relationship, Drug Gene Expression / drug effects Genetic Markers I-kappa B Proteins / metabolism Mesenchymal Stem Cells / cytology* Mesenchymal Stem Cells / drug effects* Mesenchymal Stem Cells / metabolism Mice NF-KappaB Inhibitor alpha NF-kappa B / antagonists & inhibitors NF-kappa B / metabolism Osteoblasts / cytology Osteoblasts / drug effects Osteoblasts / metabolism Osteocalcin / metabolism Osteogenesis / drug effects* Osteogenesis / genetics Osteogenesis / physiology Signal Transduction / drug effects Sp7 Transcription Factor Transcription Factors / metabolism Tumor Necrosis Factor-alpha / administration & dosage*
IF 5.753
引用数 100
WOS 分野 CELL BIOLOGY
リソース情報
ヒト・動物細胞 ST2(RCB0224)