Core Binding Factor ß Plays a Critical Role During Chondrocyte Differentiation.
J Cell Physiol
; 231(1): 162-71, 2016 Jan.
Article
em En
| MEDLINE
| ID: mdl-26058470
ABSTRACT
Core binding factor ß (Cbfß) is a partner protein of Runx family transcription factors with minimally characterized function in cartilage. Here we address the role of Cbfß in cartilage by generating chondrocyte-specific Cbfß-deficient mice (Cbfb(Δch/Δch) ) from Cbfb-floxed mice crossed with mice expressing Cre from the Col2a1 promoter. Cbfb(Δch/Δch) mice died soon after birth and exhibited delayed endochondral bone formation, shorter appendicular skeleton length with increased proliferative chondrocytes, and nearly absent hypertrophic chondrocyte zones. Immunohistochemical and quantitative real-time PCR analyses showed that the number and size of proliferative chondrocytes increased and the expression of chondrocyte maturation markers at the growth plates, including Runx2, osterix, and osteopontin, significantly diminished in Cbfb(Δch/Δch) mice compared to wild type mice. With regard to signaling pathways, both PTHrP-Ihh and BMP signaling were compromised in Cbfb(Δch/Δch) mice. Mechanistically, Cbfß deficiency in chondrocytes caused a decrease of protein levels of Runx transcription factors by accelerating polyubiquitination-mediated proteosomal degradation in vitro. Indeed, Runx2 and Runx3, but not Runx1, decreased in Cbfb(Δch/Δch) mice. Collectively, these findings indicate that Cbfß plays a critical role for chondrocyte differentiation through stabilizing Runx2 and Runx3 proteins in cartilage.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Diferenciação Celular
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Condrócitos
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Condrogênese
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Subunidade beta de Fator de Ligação ao Core
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Lâmina de Crescimento
Limite:
Animals
Idioma:
En
Revista:
J Cell Physiol
Ano de publicação:
2016
Tipo de documento:
Article