Repurpose dasatinib and quercetin: Targeting senescent cells ameliorates postmenopausal osteoporosis and rejuvenates bone regeneration.
Bioact Mater
; 25: 13-28, 2023 Jul.
Article
en En
| MEDLINE
| ID: mdl-37056256
ABSTRACT
Clinical therapies developed for estrogen-deficiency-driven postmenopausal osteoporosis (PMO) and related diseases, such as bone degeneration, show multiple adverse effects nowadays. Targeting senescent cells (SnCs) and the consequent senescence-associated secretory phenotype (SASP) with a combination of dasatinib and quercetin (DQ) is a recently developed novel therapy for multiple age-related diseases. Herein, we found that estrogen deficiency induced-bone loss was attributed to a pro-inflammatory microenvironment with SASP secretions and accelerated SnC accumulation, especially senescent mesenchymal stem cells (MSCs) characterized by exhaustion and dysfunction in middle aged rats. Systematically targeting SnCs with DQ strikingly ameliorated PMO and restored MSC function. Local administration of DQ and bone morphogenetic protein 2 (BMP2) in combination promoted osteogenic differentiation of MSCs and rejuvenated osteoporotic bone regeneration. Our results repurposed DQ as an attractive therapy for treating PMO and related diseases.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
Bioact Mater
Año:
2023
Tipo del documento:
Article
Pais de publicación:
CHINA
/
CN
/
REPUBLIC OF CHINA