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Title[redir]:
Evidence that TNF-β suppresses osteoblast differentiation of mesenchymal stem cells and resveratrol reverses it through modulation of NF-κB, Sirt1 and Runx2 | Cell and Tissue Research
Description:
It has been established that inflammation plays an important role in bone formation and bone loss. Although a lot is known about the role of TNF-α in bone health, very little is understood about TNF-β, also called lymphotoxin. In this report, we examine the effect of TNF-β on osteogenic differentiation of mesenchymal stem cells (MSCs) and its modulation by resveratrol. Monolayer and high-density cultures of MSCs were treated with osteogenic induction medium with/without TNF-β, Sirt1 inhibitor nicotinamide (NAM), antisense oligonucleotides against Sirt1 (ASO) and/or Sirt1 stimulator resveratrol. We found that TNF-β inhibits, in a similar way to NAM or Sirt1-ASO, the early stage of osteogenic differentiation of MSCs and this was accompanied with downregulation of bone-specific matrix, β1-integrin, Runx2 and with upregulation of NF-κB phosphorylation and NF-κB-regulated gene products involved in the inflammatory, degradative processes and apoptosis. However, resveratrol reversed TNF-β- and NAM-suppressed MSCs osteogenesis by activation of Sirt1 and Runx2 that led to osteoblast differentiation. Furthermore, downregulation of Sirt1 by mRNA inhibited the effect of resveratrol, highlighting the important impact of this enzyme in the TNF-β signaling pathway. Finally, resveratrol was able to manifest its effect both by suppression of TNF-β-induced NF-κB and through direct activation of the Sirt1 and Runx2 pathway. Thus, through these studies, we present a mechanism by which a T cell-derived cytokine, TNF-β can affect bone formation through modulation of MSCs differentiation that involves NF-κB, Sirt1, Runx2 and resveratrol reversed TNF-β-promoted impairments in MSCs osteogenesis.
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pubmed, google, scholar, cas, stem, cells, resveratrol, bone, arthritis, central, differentiation, cell, sirt, mesenchymal, factor, human, shakibaei, rheumatoid, aggarwal, tissue, article, runx, biol, res, tnfβ, inflammatory, necrosis, osteoblast, role, activation, buhrmann, osteogenic, nfkappab, chem, mobasheri, rheum, research, lymphotoxin, osteogenesis, signaling, cytokine, osteoblasts, liu, modulation, nfκb, effect, mscs, matrix, apoptosis, rev,
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tnf-α-promoted osteogenic differentiation tnf-β-induced nf-κb month download article/chapter bone marrow-derived macrophages inhibiting nf-kappab activation anti-tnf antibody therapy adipose-derived stem cells resveratrol-mediated sirt-1 interactions tumor necrosis factor-alpha resveratrol reversed tnf-β collagen-induced arthritic mice tnf-β signaling pathway exposure-adjusted pooled analyses integrin-mediated interactions randomised placebo-controlled trials cell type-specific responses tnf-induced osteoclastogenesis tnf-β inhibits nuclear factor kappab tumor necrosis factor related subjects disease-modifying antirheumatic drugs nf-kappab signaling pro-inflammatory cytokine secretion ludwig-maximilian-university munich mesenchymal stem cells nf-κb access bone-derived cells resveratrol promotes osteogenesis canine primary osteoblasts transcription factor rbp nf-kappab ligand cell-derived cytokine stem cell characteristics multipotent stem cells bone-specific matrix full article pdf privacy choices/manage cookies cell-based therapies nam-suppressed mscs osteogenesis promoting chondrogenic differentiation cell signal 25 interleukin-1beta ikappab kinase activities tissue research aims inflammatory signaling pathways bone formation based nf-κb phosphorylation involves nf-κb direct activation
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headline:Evidence that TNF-β suppresses osteoblast differentiation of mesenchymal stem cells and resveratrol reverses it through modulation of NF-κB, Sirt1 and Runx2
description:It has been established that inflammation plays an important role in bone formation and bone loss. Although a lot is known about the role of TNF-α in bone health, very little is understood about TNF-β, also called lymphotoxin. In this report, we examine the effect of TNF-β on osteogenic differentiation of mesenchymal stem cells (MSCs) and its modulation by resveratrol. Monolayer and high-density cultures of MSCs were treated with osteogenic induction medium with/without TNF-β, Sirt1 inhibitor nicotinamide (NAM), antisense oligonucleotides against Sirt1 (ASO) and/or Sirt1 stimulator resveratrol. We found that TNF-β inhibits, in a similar way to NAM or Sirt1-ASO, the early stage of osteogenic differentiation of MSCs and this was accompanied with downregulation of bone-specific matrix, β1-integrin, Runx2 and with upregulation of NF-κB phosphorylation and NF-κB-regulated gene products involved in the inflammatory, degradative processes and apoptosis. However, resveratrol reversed TNF-β- and NAM-suppressed MSCs osteogenesis by activation of Sirt1 and Runx2 that led to osteoblast differentiation. Furthermore, downregulation of Sirt1 by mRNA inhibited the effect of resveratrol, highlighting the important impact of this enzyme in the TNF-β signaling pathway. Finally, resveratrol was able to manifest its effect both by suppression of TNF-β-induced NF-κB and through direct activation of the Sirt1 and Runx2 pathway. Thus, through these studies, we present a mechanism by which a T cell-derived cytokine, TNF-β can affect bone formation through modulation of MSCs differentiation that involves NF-κB, Sirt1, Runx2 and resveratrol reversed TNF-β-promoted impairments in MSCs osteogenesis.
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headline:Evidence that TNF-β suppresses osteoblast differentiation of mesenchymal stem cells and resveratrol reverses it through modulation of NF-κB, Sirt1 and Runx2
description:It has been established that inflammation plays an important role in bone formation and bone loss. Although a lot is known about the role of TNF-α in bone health, very little is understood about TNF-β, also called lymphotoxin. In this report, we examine the effect of TNF-β on osteogenic differentiation of mesenchymal stem cells (MSCs) and its modulation by resveratrol. Monolayer and high-density cultures of MSCs were treated with osteogenic induction medium with/without TNF-β, Sirt1 inhibitor nicotinamide (NAM), antisense oligonucleotides against Sirt1 (ASO) and/or Sirt1 stimulator resveratrol. We found that TNF-β inhibits, in a similar way to NAM or Sirt1-ASO, the early stage of osteogenic differentiation of MSCs and this was accompanied with downregulation of bone-specific matrix, β1-integrin, Runx2 and with upregulation of NF-κB phosphorylation and NF-κB-regulated gene products involved in the inflammatory, degradative processes and apoptosis. However, resveratrol reversed TNF-β- and NAM-suppressed MSCs osteogenesis by activation of Sirt1 and Runx2 that led to osteoblast differentiation. Furthermore, downregulation of Sirt1 by mRNA inhibited the effect of resveratrol, highlighting the important impact of this enzyme in the TNF-β signaling pathway. Finally, resveratrol was able to manifest its effect both by suppression of TNF-β-induced NF-κB and through direct activation of the Sirt1 and Runx2 pathway. Thus, through these studies, we present a mechanism by which a T cell-derived cytokine, TNF-β can affect bone formation through modulation of MSCs differentiation that involves NF-κB, Sirt1, Runx2 and resveratrol reversed TNF-β-promoted impairments in MSCs osteogenesis.
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