TSH is a negative regulator of skeletal remodeling.
Cell
; 115(2): 151-62, 2003 Oct 17.
Article
em En
| MEDLINE
| ID: mdl-14567913
ABSTRACT
The established function of thyroid stimulating hormone (TSH) is to promote thyroid follicle development and hormone secretion. The osteoporosis associated with hyperthyroidism is traditionally viewed as a secondary consequence of altered thyroid function. We provide evidence for direct effects of TSH on both components of skeletal remodeling, osteoblastic bone formation, and osteoclastic bone resorption, mediated via the TSH receptor (TSHR) found on osteoblast and osteoclast precursors. Even a 50% reduction in TSHR expression produces profound osteoporosis (bone loss) together with focal osteosclerosis (localized bone formation). TSH inhibits osteoclast formation and survival by attenuating JNK/c-jun and NFkappaB signaling triggered in response to RANK-L and TNFalpha. TSH also inhibits osteoblast differentiation and type 1 collagen expression in a Runx-2- and osterix-independent manner by downregulating Wnt (LRP-5) and VEGF (Flk) signaling. These studies define a role for TSH as a single molecular switch in the independent control of both bone formation and resorption.
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Base de dados:
MEDLINE
Assunto principal:
Tireotropina
/
Remodelação Óssea
/
Proteínas de Peixe-Zebra
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article