Msx2 mediates the inhibitory action of TNF-alpha on osteoblast differentiation
Experimental & Molecular Medicine
; : 437-445, 2010.
Article
Dans En
| WPRIM
| ID: wpr-27759
Responsable en Bibliothèque :
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.
Texte intégral:
1
Indice:
WPRIM
Sujet Principal:
Ostéoblastes
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Souris transgéniques
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Régulation négative
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Différenciation cellulaire
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Cellules cultivées
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Régulation de l'expression des gènes
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Facteur de nécrose tumorale alpha
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Protéines à homéodomaine
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Techniques de culture cellulaire
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Petit ARN interférent
Limites du sujet:
Animals
langue:
En
Texte intégral:
Experimental & Molecular Medicine
Année:
2010
Type:
Article