Msx2 mediates the inhibitory action of TNF-alpha on osteoblast differentiation
Experimental & Molecular Medicine
; : 437-445, 2010.
Article
em En
| WPRIM
| ID: wpr-27759
Biblioteca responsável:
WPRO
ABSTRACT
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. TNF-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-kappaB and the JNK pathways. Inhibition of NF-kappaB 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-kappaB 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-kappaB pathway is responsible for Msx2 induction.
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Texto completo:
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Base de dados:
WPRIM
Assunto principal:
Osteoblastos
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Camundongos Transgênicos
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Regulação para Baixo
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Diferenciação Celular
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Células Cultivadas
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Regulação da Expressão Gênica
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Fator de Necrose Tumoral alfa
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Proteínas de Homeodomínio
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Técnicas de Cultura de Células
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RNA Interferente Pequeno
Limite:
Animals
Idioma:
En
Revista:
Experimental & Molecular Medicine
Ano de publicação:
2010
Tipo de documento:
Article