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Trichostatin A-mediated upregulation of p21
Article en En | WPRIM | ID: wpr-90611
Biblioteca responsable: WPRO
ABSTRACT
Histone deacetylase inhibitors (HDIs), a new class of anti-cancer agents, have been reported to suppress formation of osteoclast precursors and their fusion into multinucleated cells. However, little is known about the effect of HDIs on mature osteoclasts, which may have significance for their therapeutic use. Here, we demonstrate a novel action of HDIs on osteoclast apoptosis. Primary multinucleated mature osteoclasts were prepared from mouse bone marrow cells. Treatment of osteoclasts with the HDI trichostatin A (TSA) caused apoptosis, as confirmed by annexin V staining and caspase activation. TSA caused the upregulation of p21WAF1 in osteoclasts. To understand the role of p21(WAF1) upregulation in TSA-treated osteoclasts, shRNA against p21(WAF1)-containing lentivirus was introduced into osteoclasts. The suppression of p21(WAF1) decreased TSA-directed osteoclast apoptosis. Collectively, our results provide evidence that TSA causes osteoclast apoptosis, which involves, in part, TSA-induced upregulation of p21(WAF1), and strongly supports HDIs as potential therapeutic agents for excessive bone resorption.
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Texto completo: 1 Índice: WPRIM Asunto principal: Osteoclastos / Resorción Ósea / ARN Mensajero / Regulación hacia Arriba / Regulación de la Expresión Génica / Apoptosis / Inhibidor p21 de las Quinasas Dependientes de la Ciclina / Ligando RANK / Ácidos Hidroxámicos Límite: Animals / Female / Humans Idioma: En Revista: Experimental & Molecular Medicine Año: 2007 Tipo del documento: Article
Texto completo: 1 Índice: WPRIM Asunto principal: Osteoclastos / Resorción Ósea / ARN Mensajero / Regulación hacia Arriba / Regulación de la Expresión Génica / Apoptosis / Inhibidor p21 de las Quinasas Dependientes de la Ciclina / Ligando RANK / Ácidos Hidroxámicos Límite: Animals / Female / Humans Idioma: En Revista: Experimental & Molecular Medicine Año: 2007 Tipo del documento: Article