CRTC2 suppresses BMP2-induced osteoblastic differentiation via Smurf1 expression in MC3T3-E1 cells.
Life Sci
; 214: 70-76, 2018 Dec 01.
Article
en En
| MEDLINE
| ID: mdl-30449452
ABSTRACT
AIMS:
CREB (cAMP response element-binding protein)-regulated transcription coactivator (CRTC2) has been reported to act as a coactivator of CREB during gluconeogenesis. The role of CRTC2 in osteoblastic differentiation has not yet been elucidated. The aim of this study is to identify the mechanism of CRTC2 in osteoblast differentiation. MAINMETHODS:
The mRNA expression was determined by RT-PCR and qPCR. Protein levels were measured using Western blot assay. Alkaline phosphatase (ALP) staining was performed to evaluate ALP activity. Alizarin red S (ARS) staining was performed to measure extracellular mineralization. Transcriptional activity was detected using a luciferase assay. KEYFINDINGS:
In the present study, TNF-α was found to stimulate CRTC2 expression. However, TNF-α did not increase the gene expression of osteoblast differentiation markers and inhibited BMP2-induced osteoblastic differentiation. Overexpression of CRTC2 decreased the expression of osteogenic genes, ALP activity and extracellular matrix mineralization. Knockdown of CRTC2 restored BMP2-induced osteogenic gene expression and ALP activity. CRTC2 increased Smurf1 mRNA expression, Smurf 1 promoter activity, and protein level. Furthermore, Smurf 1 decreased Smad 1/5/9 protein levels. These results suggest that CRTC2 decreased BMP2-induced osteoblastic differentiation via Smurf 1 expression.SIGNIFICANCE:
Our results indicate that CRTC2 regulates the expression of Smurf1 in osteoblast differentiation.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Osteoblastos
/
Factores de Transcripción
/
Ubiquitina-Proteína Ligasas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Life Sci
Año:
2018
Tipo del documento:
Article