Arsenic trioxide and microRNA-204 display contrary effects on regulating adipogenic and osteogenic differentiation of mesenchymal stem cells in aplastic anemia.
Acta Biochim Biophys Sin (Shanghai)
; 46(10): 885-93, 2014 Oct.
Article
en En
| MEDLINE
| ID: mdl-25187411
ABSTRACT
Our previous studies have demonstrated that arsenic trioxide (ATO) had the clinical efficacy in treating patients with aplastic anemia (AA). However, the mechanisms remain to be elucidated. The important components of the bone marrow hematopoietic microenvironment, bone marrow mesenchymal stem cells (BMSCs), are often altered in AA patients. In this study, it was found that AA BMSCs were prone to be induced into adipocytes rather than osteoblasts. ATO treatment can at least partially restore the differentiation imbalance of AA BMSCs. We further identified miR-204 as a key regulator in AA BMSC differentiation. Luciferase reporter assay showed that miR-204 could directly bind to the 3'-untranslated region of Runx2 mRNA, a key transcription factor regulating osteogenesis. Moreover, adipogenic differentiation was promoted and osteogenic differentiation was inhibited in miR-204 over-expressed cells, whereas osteogenesis was enhanced and adipocyte formation was inhibited in cells that lost miR-204 function, which suggested its endogenous function. Together we showed that ATO could inhibit adipogenic differentiation, but promote osteogenic differentiation in AA BMSCs, providing a possible explanation for ATO clinical efficacy in AA patients. MiR-204 plays a key role in regulating BMSCs differentiation, and down-regulating miR-204 expression might be a novel strategy to treat AA.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Óxidos
/
Arsenicales
/
Células de la Médula Ósea
/
Diferenciación Celular
/
Tejido Adiposo
/
MicroARNs
/
Células Madre Mesenquimatosas
/
Anemia Aplásica
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Acta Biochim Biophys Sin (Shanghai)
Asunto de la revista:
BIOFISICA
/
BIOQUIMICA
Año:
2014
Tipo del documento:
Article
País de afiliación:
China