NF-kappaB activation stimulates osteogenic differentiation of mesenchymal stem cells derived from human adipose tissue by increasing TAZ expression.
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.
Cho
Hyun Hwa
HH
Department of Physiology, School of Medicine, Pusan National University, Yangsan, Korea.
Shin
Keun Koo
KK
Kim
Yeon Jeong
YJ
Song
Ji Sun
JS
Kim
Jong Myung
JM
Bae
Yong Chan
YC
Kim
Chi Dae
CD
Jung
Jin Sup
JS
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
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