Osterix and RUNX2 are Transcriptional Regulators of Sclerostin in Human Bone.
Calcif Tissue Int
; 99(3): 302-9, 2016 09.
Article
em En
| MEDLINE
| ID: mdl-27154028
ABSTRACT
Sclerostin, encoded by the SOST gene, works as an inhibitor of the Wnt pathway and therefore is an important regulator of bone homeostasis. Due to its potent action as an inhibitor of bone formation, blocking sclerostin activity is the purpose of recently developed anti-osteoporotic treatments. Two bone-specific transcription factors, RUNX2 and OSX, have been shown to interact and co-ordinately regulate the expression of bone-specific genes. Although it has been recently shown that sclerostin is targeted by OSX in mice, there is currently no information of whether this is also the case in human cells. We have identified SP-protein family and AML1 consensus binding sequences at the human SOST promoter and have shown that OSX, together with RUNX2, binds to a specific region close to the transcription start site. Furthermore, we show that OSX and RUNX2 activate SOST expression in a co-ordinated manner in vitro and that SOST expression levels show a significant positive correlation with OSX/RUNX2 expression levels in human bone. We also confirmed previous results showing an association of several SOST/RUNX2 polymorphisms with bone mineral density.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Osso e Ossos
/
Proteínas Morfogenéticas Ósseas
/
Subunidade alfa 1 de Fator de Ligação ao Core
/
Fator de Transcrição Sp7
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Calcif Tissue Int
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Espanha