Enhanced autophagy suppresses inflammation-mediated bone loss through ROCK1 signaling in bone marrow mesenchymal stem cells.
Cells Dev
; 167: 203687, 2021 09.
Article
en En
| MEDLINE
| ID: mdl-34058434
ABSTRACT
Bone marrow mesenchymal stem cells (BMSCs) have strong proliferative ability and multi-directional differentiation potential. Osteoarthritis is a degenerative joint disease that is closely related to the loss of osteogenic differentiation function of BMSCs. Autophagy, plays a crucial role in the maintenance of cellular functions, but its regulatory mechanism during the osteogenic differentiation of BMSCs remains unclear. In this study, we analyzed the differential gene networks and pathways during BMSC osteogenesis using bioinformatics, and further validated the regulatory roles of autophagy during the osteogenic differentiation of BMSCs in inflammatory condition in vitro. We found that Tumor necrosis factor alpha (TNF-α) treatment led to actin cytoskeleton rearrangements and inhibited osteogenic differentiation in BMSCs. In addition, TNF-α enhanced Rho-associated protein kinase 1 (ROCK1) expression and decreased autophagy activation. ROCK1 knockdown reduced Endoplasmic Reticulum stress (ER stress) and promoted autophagy, resulting reversion of osteogenic differentiation in BMSCs under inflammatory condition. Rapamycin reversed the TNF-α-induced decrease in osteogenesis of BMSCs, assessed by alkaline phosphatase (ALP) activity and Alizarin staining. Autophagy treated with inhibitor 3-Methyladenine (3-MA) further increased TNF-α-induced osteogenesis inhibition of BMSCs. Collectively, these results indicate that ER stress and dysfunction of autophagy promote inflammation-induced bone loss through the activation of ROCK1 signaling in BMSCs.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
6_ODS3_enfermedades_notrasmisibles
Problema de salud:
6_endocrine_disorders
/
6_other_malignant_neoplasms
Asunto principal:
Autofagia
/
Resorción Ósea
/
Transducción de Señal
/
Quinasas Asociadas a rho
/
Células Madre Mesenquimatosas
/
Inflamación
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Cells Dev
Año:
2021
Tipo del documento:
Article
País de afiliación:
China