Zfp521 is a target gene and key effector of parathyroid hormone-related peptide signaling in growth plate chondrocytes.
Dev Cell
; 19(4): 533-46, 2010 Oct 19.
Article
em En
| MEDLINE
| ID: mdl-20951345
ABSTRACT
In the growth plate, the interplay between parathyroid hormone-related peptide (PTHrP) and Indian hedgehog (Ihh) signaling tightly regulates chondrocyte proliferation and differentiation during longitudinal bone growth. We found that PTHrP increases the expression of Zfp521, a zinc finger transcriptional coregulator, in prehypertrophic chondrocytes. Mice with chondrocyte-targeted deletion of Zfp521 resembled PTHrP(-/-) and chondrocyte-specific PTHR1(-/-) mice, with decreased chondrocyte proliferation, early hypertrophic transition, and reduced growth plate thickness. Deleting Zfp521 increased expression of Runx2 and Runx2 target genes, and decreased Cyclin D1 and Bcl-2 expression while increasing Caspase-3 activation and apoptosis. Zfp521 associated with Runx2 in chondrocytes, antagonizing its activity via an HDAC4-dependent mechanism. PTHrP failed to upregulate Cyclin D1 and to antagonize Runx2, Ihh, and collagen X expression when Zfp521 was absent. Thus, Zfp521 is an important PTHrP target gene that regulates growth plate chondrocyte proliferation and differentiation.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
6_ODS3_enfermedades_notrasmisibles
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Transdução de Sinais
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Condrócitos
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Proteína Relacionada ao Hormônio Paratireóideo
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Lâmina de Crescimento
Limite:
Animals
Idioma:
En
Revista:
Dev Cell
Ano de publicação:
2010
Tipo de documento:
Article