title: NF-kappaB activation stimulates osteogenic differentiation of mesenchymal stem cells derived from human adipose tissue by increasing TAZ expression.
abstract: Tumor necrosis factor-alpha (TNF-alpha) is a skeletal catabolic agent that stimulates osteoclastogenesis and inhibits osteoblast function. Although TNF-alpha inhibits the mineralization of osteoblasts, the effect of TNF-alpha on mesenchymal stem cells (MSC) is not clear. In this study, we determined the effect of TNF-alpha on osteogenic differentiation of stromal cells derived from human adipose tissue (hADSC) and the role of NF-kappaB activation on TNF-alpha activity. TNF-alpha treatment dose-dependently increased osteogenic differentiation over the first 3 days of treatment. TNF-alpha activated ERK and increased NF-kappaB promoter activity. PDTC, an NF-kappaB inhibitor, blocked the osteogenic differentiation induced by TNF-alpha and TLR-ligands, but U102, an ERK inhibitor, did not. Overexpression of miR-146a induced the inhibition of IRAK1 expression and inhibited basal and TNF-alpha- and TLR ligand-induced osteogenic differentiation. TNF-alpha and TLR ligands increased the expression of transcriptional coactivator with PDZ-binding motif (TAZ), which was inhibited by the addition of PDTC. A ChIP assay showed that p65 was bound to the TAZ promoter. TNF-alpha also increased osteogenic differentiation of human gastroepiploic artery smooth muscle cells. Our data indicate that TNF-alpha enhances osteogenic differentiation of hADSC via the activation of NF-kappaB and a subsequent increase of TAZ expression.
authors.affiliation: Department of Physiology, School of Medicine, Pusan National University, Yangsan, Korea.
authors.forename: Hyun Hwa
authors.initials: HH
authors.lastname: Cho
authors.forename: Keun Koo
authors.initials: KK
authors.lastname: Shin
authors.forename: Yeon Jeong
authors.initials: YJ
authors.lastname: Kim
authors.forename: Ji Sun
authors.initials: JS
authors.lastname: Song
authors.forename: Jong Myung
authors.initials: JM
authors.lastname: Kim
authors.forename: Yong Chan
authors.initials: YC
authors.lastname: Bae
authors.forename: Chi Dae
authors.initials: CD
authors.lastname: Kim
authors.forename: Jin Sup
authors.initials: JS
authors.lastname: Jung
mesh_terms: D000217:Acyltransferases; D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D001665:Binding Sites; D002070:Butadienes / Q000494:pharmacology; D002114:Calcinosis / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D006801:Humans; D053592:Interleukin-1 Receptor-Associated Kinases / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D010012:Osteogenesis / Q000187:drug effects; D011401:Promoter Regions, Genetic; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D034622:RNA Interference; D011994:Recombinant Proteins / Q000378:metabolism; D013859:Thiocarbamates / Q000494:pharmacology; D013997:Time Factors; D051193:Toll-Like Receptors / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D002070:Butadienes; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D011759:Pyrrolidines; C498143:RELA protein, human; D011994:Recombinant Proteins; D013859:Thiocarbamates; D051193:Toll-Like Receptors; D051996:Transcription Factor RelA; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; C113580:U 0126; C020972:pyrrolidine dithiocarbamic acid; D000217:Acyltransferases; C108675:TAFAZZIN protein, human; C507768:IRAK1 protein, human; D053592:Interleukin-1 Receptor-Associated Kinases; D048049:Extracellular Signal-Regulated MAP Kinases