Dickkopf-1 is a master regulator of joint remodeling.
Nat Med
; 13(2): 156-63, 2007 Feb.
Article
em En
| MEDLINE
| ID: mdl-17237793
ABSTRACT
Degenerative and inflammatory joint diseases lead to a destruction of the joint architecture. Whereas degenerative osteoarthritis results in the formation of new bone, rheumatoid arthritis leads to bone resorption. The molecular basis of these different patterns of joint disease is unknown. By inhibiting Dickkopf-1 (DKK-1), a regulatory molecule of the Wnt pathway, we were able to reverse the bone-destructive pattern of a mouse model of rheumatoid arthritis to the bone-forming pattern of osteoarthritis. In this way, no overall bone erosion resulted, although bony nodules, so-called osteophytes, did form. We identified tumor necrosis factor-alpha (TNF) as a key inducer of DKK-1 in the mouse inflammatory arthritis model and in human rheumatoid arthritis. These results suggest that the Wnt pathway is a key regulator of joint remodeling.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Osteogênese
/
Artrite Reumatoide
/
Reabsorção Óssea
/
Transdução de Sinais
/
Fator de Necrose Tumoral alfa
/
Peptídeos e Proteínas de Sinalização Intercelular
/
Proteínas Wnt
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article