Advanced bone formation in mice with a dominant-negative mutation in the thyroid hormone receptor ß gene due to activation of Wnt/ß-catenin protein signaling.
J Biol Chem
; 287(21): 17812-17822, 2012 May 18.
Article
em En
| MEDLINE
| ID: mdl-22442145
ABSTRACT
Thyroid hormone (T(3)) acts in chondrocytes and bone-forming osteoblasts to control bone development and maintenance, but the signaling pathways mediating these effects are poorly understood. Thrb(PV/PV) mice have a severely impaired pituitary-thyroid axis and elevated thyroid hormone levels due to a dominant-negative mutant T(3) receptor (TRß(PV)) that cannot bind T(3) and interferes with the actions of wild-type TR. Thrb(PV/PV) mice have accelerated skeletal development due to unknown mechanisms. We performed microarray studies in primary osteoblasts from wild-type mice and Thrb(PV/PV) mice. Activation of the canonical Wnt signaling in Thrb(PV/PV) mice was confirmed by in situ hybridization analysis of Wnt target gene expression in bone during postnatal growth. By contrast, T(3) treatment inhibited Wnt signaling in osteoblastic cells, suggesting that T(3) inhibits the Wnt pathway by facilitating proteasomal degradation of ß-catenin and preventing its accumulation in the nucleus. Activation of the Wnt pathway in Thrb(PV/PV) mice, however, results from a gain of function for TRß(PV) that stabilizes ß-catenin despite the presence of increased thyroid hormone levels. These studies demonstrate novel interactions between T(3) and Wnt signaling pathways in the regulation of skeletal development and bone formation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Osteoblastos
/
Osteogênese
/
Hipófise
/
Receptores beta dos Hormônios Tireóideos
/
Beta Catenina
/
Via de Sinalização Wnt
/
Mutação
Limite:
Animals
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article