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KMID : 0620920100420060437
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Experimental & Molecular Medicine
2010 Volume.42 No. 6 p.437 ~ p.445
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Msx2 mediates the inhibitory action of TNF-α on osteoblast differentiation
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Lee Hye-Lim
Yi Tac-Ghee
Woo Kyung-Mi
Ryoo Hyun-Mo
Kim Gwan-Shik
Baek Jeong-Hwa
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Abstract
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TNF-α, a proinflammatory cytokine, inhibits osteoblast differentiation under diverse inflammatory conditions; however, the underlying mechanisms in terms of the TNF-α signaling pathway remain unclear. In this study, we examined the role of Msx2 in TNF-α-mediated inhibition of alkaline phosphatase (ALP) expression and the signaling pathways involved. TNF-α down-regulated ALP expression induced by bone morphogenetic protein 2 (BMP2) in C2C12 and Runx2-/- calvarial cells. Over-expression of Msx2 suppressed BMP2-induced ALP expression. Furthermore, TNF-α induced Msx2 expression, and the knockdown of Msx2 by small interfering RNAs rescued ALP expression, which was inhibited by TNF-α. TNF-α activated the NF-κB and the JNK pathways. Inhibition of NF-κB or JNK activation reduced the inhibitory effect of TNF-α on ALP expression, whereas TNF-α-induced Msx2 expression was only suppressed by the inhibition of the NF-κB pathway. Taken together, these results indicate that Msx2 mediates the inhibitory action of TNF-α on BMP2-regulated osteoblast differentiation and that the TNF-α-activated NF-κB pathway is responsible for Msx2 induction.
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KEYWORD
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alkaline phosphatase, bone morphogenetic protein 2, cell differentiation, Msx2 protein, NF-κB, osteoblasts, tumor necrosis factor-α
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