EGR1 plays an important role in BMP9-mediated osteoblast differentiation by promoting SMAD1/5 phosphorylation.
FEBS Lett
; 596(13): 1720-1732, 2022 07.
Article
en En
| MEDLINE
| ID: mdl-35594155
ABSTRACT
Bone morphogenetic proteins (BMPs) are essential regulators of skeletal homeostasis, and BMP9 is the most potently osteogenic among them. Here, we found that BMP9 and BMP2 rapidly induced early growth response 1 (EGR1) protein expression in osteoblasts through MEK/ERK pathway-dependent transcriptional activation. Knock-down of EGR1 using siRNA significantly inhibited BMP9-induced matrix mineralization and osteogenic marker gene expression in osteoblasts. Knock-down of EGR1 significantly reduced SMAD1/5 phosphorylation and inhibited the expression of their transcriptional targets in osteoblasts stimulated by BMP9. In contrast, forced EGR1 overexpression in osteoblasts enhanced BMP9-mediated osteoblast differentiation and SMAD1/5 phosphorylation. An intracellular association between EGR1 and SMAD1/5 was identified using immunoprecipitation assays. These results indicated that EGR1 plays an important role in BMP9-stimulated osteoblast differentiation by enhancing SMAD1/5 phosphorylation.
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Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Transducción de Señal
/
Factor 2 de Diferenciación de Crecimiento
Tipo de estudio:
Prognostic_studies
Idioma:
En
Año:
2022
Tipo del documento:
Article