RSK2 protects mice against TNF-induced bone loss.
J Cell Sci
; 125(Pt 9): 2160-71, 2012 May 01.
Article
em En
| MEDLINE
| ID: mdl-22344264
ABSTRACT
Tumor necrosis factor (TNF)-α is a key cytokine regulator of bone and mediates inflammatory bone loss. The molecular signaling that regulates bone loss downstream of TNF-α is poorly defined. Here, we demonstrate that inactivating the pro-osteoblastogenic ERK-activated ribosomal S6 kinase RSK2 leads to a drastically accelerated and amplified systemic bone loss in mice ectopically expressing TNF-α [human TNF transgenic (hTNFtg) mice]. The phenotype is associated with a decrease in bone formation because of fewer osteoblasts as well as a drastically increased bone destruction by osteoclasts. The molecular basis of this phenotype is a cell autonomous increased sensitivity of osteoblasts and osteocytes to TNF-induced apoptosis combined with an enhancement of their osteoclast supportive activity. Thus, RSK2 exerts a strong negative regulatory loop on TNF-induced bone loss.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Reabsorção Óssea
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Fator de Necrose Tumoral alfa
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Proteínas Quinases S6 Ribossômicas 90-kDa
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article