Lentivirus-Mediated Small Interfering RNA Targeting Piezo1 Inhibits Cartilage Matrix degeneration in Osteoarthritis Chondrocytes

Osteoarthritis (OA) is triggered by abnormal distraction stress, which eventually leads to cartilage degeneration. However, it remains unclear how the mechanical stress factor acts an effect on the destruction of the cartilage matrix. As a kind of mechanical sensitive ion channel protein, Piezo1 has the ability to sense and transmit mechanical signals to cells. Previous studies have found that the stress sensitivity of Piezo1 is closely related to the directionality of mechanical stress and the presence of extracellular matrix. This research aimed to explore the role of lentivirus-mediated Piezo1-siRNA transfection in extracellular matrix in chondrocytes of cultured osteoarthritis in vitro and to investigate the effect of Piezo1 on the progression of osteoarthritis. In this study, we demonstrated that the expression of Piezo1 mRNA in transfection group was significantly decreased after 24h mechanical stress was applied. However, the expression trend of collagen II and aggrecan was opposite to that of Piezo1, matrix metalloproteinase-13 (MMP-13), and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5). Our results indicate that Piezo1 could be used as a possible therapeutic target to attenuate the destruction of cartilage matrix induced by mechanical stress. Lentiviral-mediated Piezo1-siRNA can effectively interfere with the expression of Piezo1 and protect the expression of the extracellular cartilage matrix.