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
Buhrmann ConstanzeMehdi Shakibaei

Abstract

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 T...Continue Reading

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Citations

Feb 16, 2021·Frontiers in Cell and Developmental Biology·Béryl Laplace-BuilhéFarida Djouad
Apr 4, 2021·International Journal of Molecular Sciences·Dulshara Sachini AmarasekaraJaerang Rho
Jul 3, 2021·International Journal of Molecular Sciences·Marco Ponzetti, Nadia Rucci
Jul 25, 2021·International Journal of Molecular Sciences·Constanze BuhrmannMehdi Shakibaei

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Methods Mentioned

BETA
FCS
transfection
electron microscopy
electrophoresis
Immunoprecipitation
light microscopy
transmission electron microscopy
co-immunoprecipitation
acetylation

Software Mentioned

SPSS

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