FFAs-ROS-ERK/P38 pathway plays a key role in adipocyte lipotoxicity on osteoblasts in co-culture.
Biochimie
; 101: 123-31, 2014 Jun.
Article
en En
| MEDLINE
| ID: mdl-24424405
ABSTRACT
The accumulation of adipocytes in bone marrow is common in a variety of pathophysiological conditions, including obesity, insulin resistance, type 2 diabetes, and aging. Adipocytes in bone marrow exhibit severe adverse effect on osteoblast differentiation, proliferation, and function. However, the molecular mechanism of adipocytes lipotoxicity on osteoblasts is still far from completely understood. The present study was designed to investigate the signaling pathway responsible for adipocytes lipotoxicity on osteoblasts. Using a co-culture system, we have identified that free fatty acids (FFAs) released by the adipocytes inhibited osteoblasts proliferation and function and induced osteoblasts apoptosis, evidenced by decreased cell viability/proliferation, ALP activity, expression of runt-related transcription factor 2 (RunX2), type I collagen (ColA1) and osteocalcin and alizarin red staining. Dexamethasone (Dex) promoted the inhibitory effect of adipocytes on osteoblasts through stimulating FFAs release. Dex-exacerbated FFAs release from adipocytes contributes to reactive oxygen species (ROS) production. In the co-culture system, the phosphorylation of extracellular signal-regulated kinase (ERK)/P38 was increased and inhibition of ERK/P38 significantly suppressed adipocytes lipotoxicity. FFAs-generated ROS was responsible for adipocytes-induced activation of ERK/P38 signaling. In conclusion, FFAs-ROS-ERK/P38 pathway plays a key role in adipocyte lipotoxicity on osteoblasts in co-culture. The evidence provides new insights into the mechanisms underlying the lipotoxic effect of adipocytes on bone within the marrow microenvironment and prevention of lipotoxicity on bone metabolism.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Osteoblastos
/
Especies Reactivas de Oxígeno
/
Adipocitos
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Sistema de Señalización de MAP Quinasas
/
Ácidos Grasos no Esterificados
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Biochimie
Año:
2014
Tipo del documento:
Article