Msx2 mediates the inhibitory action of TNF-alpha on osteoblast differentiation

作者：Lee Hye Lim; Yi TaoGhee; Woo Kyung Mi; Ryoo Hyun Mo; Kim Gwan Shik; Baek Jeong Hwa^*

来源：Experimental and Molecular Medicine, 2010, 42(6): 437-445.

DOI：10.3858/emm.2010.42.6.045

• alkaline phosphatase
• bone morphogenetic protein 2
• cell differentiation
• Msx2 protein
• NF-kappa B
• osteoblasts
• tumor necrosis factor-alpha

TNF-alpha, a proinflammatory cytokine, inhibits osteoblast differentiation under diverse inflammatory conditions; however, the underlying mechanisms in terms of the TNF-alpha signaling pathway remain unclear. In this study, we examined the role of Msx2 in TNF-alpha-mediated inhibition of alkaline phosphatase (ALP) expression and the signaling pathways involved. INF-alpha 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-alpha induced Msx2 expression, and the knockdown of Msx2 by small interfering RNAs rescued ALP expression, which was inhibited by TNF-alpha. TNF-alpha activated the NF-kappa B and the JNK pathways. Inhibition of NF-kappa B or JNK activation reduced the inhibitory effect of TNF-alpha on ALP expression, whereas TNF-alpha-induced Msx2 expression was only suppressed by the inhibition of the NF-kappa B pathway. Taken together, these results indicate that Msx2 mediates the inhibitory action of TNF-alpha on BMP2-regulated osteoblast differentiation and that the TNF-alpha-activated NF-kappa B pathway is responsible for Msx2 induction.

• 出版日期2010-6-30