LncRNA PVT1 regulates biological function of osteoarthritis cells by regulating miR-497/AKT3 axis.

Abstract

Growing evidence indicates that lncRNAs are involved in the progression of several diseases, including osteoarthritis (OA). However, the role of the lncRNA PVT1 in OA is still unclear. The present study was aimed at exploring the impact of PVT1 on OA progression, along with potential underlying mechanisms. PVT1 expression levels in articular cartilage tissue of OA patients and non-OA patients were evaluated. To assess the proliferation and apoptosis of chondrocytes subject to treatment, PVT1, miR-497, and AKT3 were either knocked down or upregulated in IL-1β-induced chondrocytes. The variables detected were changes in levels of AKT3 and extracellular matrix (ECM)-related factors (including aggrecan, collagen Type II, and MMP-9). Elevated PVT1 levels were found in cartilage tissue of OA patients and IL-1β-induced chondrocytes. It was also observed that PVT1 knockdown and miR-497 upregulation led to enhanced cell proliferation and suppressed apoptosis. In addition, a decrease in aggrecan and collagen type II levels and an increase in MMP-9 levels were observed in IL-1β-induced chondrocytes. A dual luciferase reporter assay was performed to identify the factors that interacted with miR-497, PVT1, and AKT3. It was observed through rescue experiments that enhancing AKT3 expression or knocking down miR-497 could reverse the impacts of PVT1 knockdown in IL-1β-induced chondrocytes. An upregulation of PVT1 is observed in OA patients. On the other hand, PVT1 knockdown can decrease the effects of IL-1β on the proliferation, apoptosis, and expression of ECM-related proteins of chondrocytes through the regulation of the miR-497/AKT3 axis. PVT1 levels are elevated in the cartilage tissue of OA patients and IL-1β-induced chondrocytes. PVT1 knockdown alleviates the effects of IL-1β treatment on the proliferation and apoptosis of chondrocytes and ECM degradation in chondrocytes by regulating the miR-497/AKT3 axis.