MicroRNA 495 enhances chondrocyte apoptosis, senescence and promotes the progression of osteoarthritis by targeting AKT1.
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.
American journal of translational research