MicroRNA-495 enhances chondrocyte apoptosis, senescence and promotes the progression of osteoarthritis by targeting AKT1.
Am J Transl Res
; 11(4): 2232-2244, 2019.
Article
em En
| MEDLINE
| ID: mdl-31105831
ABSTRACT
Osteoarthritis (OA) is a common multifactorial degenerative articular disease among the aging population. The current investigation aimed to elucidate the function of microRNA-495 (miR-495) in the development of OA. We found that miR-495 was upregulated in the cartilage of OA patients. Transfection of a miR-495 mimic into rat primary chondrocytes, human chondrocytes (HC) and SW1353 chondrosarcoma cells inhibited AKT1 expression, proliferation and scratch wound closure and induced apoptosis. Transfection of a miR-495 inhibitor produced an opposite effect. Furthermore, the production of cartilage degeneration-related substances was modified by miR-495. Luciferase reporter gene assay revealed that AKT1 is directly repressed by miR-495. Moreover, the levels of AKT1, p-S6 and p-mTOR diminished in chondrocytes overexpressing miR-495. AKT1 overexpression amplified p-S6 and p-mTOR levels as well as abolished miR-495 mimic-induced apoptosis and inhibition of proliferation. In the surgically induced rat OA model, apoptosis of chondrocytes and cartilage degeneration were remedied by the administration of a miR-495 antagomir. Moreover, there was an increased expression of AKT1. These findings indicate that miR-495 induces OA by targeting AKT1 and regulating the AKT/mTOR pathway. Therefore, miR-495 may be a prospective target for OA treatment.
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1
Base de dados:
MEDLINE
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Am J Transl Res
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
China