NF-κB activation stimulates osteogenic differentiation of mesenchymal stem cells derived from human adipose tissue by increasing TAZ expression.

Tumor necrosis factor-alpha (TNF-α) is a skeletal catabolic agent that stimulates osteoclastogenesis and inhibits osteoblast function. Although TNF-α inhibits the mineralization of osteoblasts, the effect of TNF-α on mesenchymal stem cells (MSC) is not clear. In this study, we determined the effect of TNF-α on osteogenic differentiation of stromal cells derived from human adipose tissue (hADSC) and the role of NF-κB activation on TNF-α activity. TNF-α treatment dose-dependently increased osteogenic differentiation over the first 3 days of treatment. TNF-α activated ERK and increased NF-κB promoter activity. PDTC, an NF-κB inhibitor, blocked the osteogenic differentiation induced by TNF-α 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-α- and TLR ligand-induced osteogenic differentiation. TNF-α 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-α also increased osteogenic differentiation of human gastroepiploic artery smooth muscle cells. Our data indicate that TNF-α enhances osteogenic differentiation of hADSC via the activation of NF-κB and a subsequent increase of TAZ expression. J. Cell. Physiol. 223: 168–177, 2010. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]