RNA-binding proteins (RBPs) have been recently proven to be involved in the pathogenesis of several diseases. However, few studies elaborated RBPs in regulating osteoarthritis. This study aims to define the function and mechanism of RBPs-PUM2 in chondrocyte apoptosis during osteoarthritis.Cartilage tissue samples and human juvenile chondrocyte cell line C28/I2 were collected for further study. PUM2 expression in the human tissues and cells was determined using qRT-PCR. Chondrocyte viability and apoptosis were determined by MTT and flow cytometry. ROS generation was determined by flow cytometry. The regulation of PUM2 on FOXO3 translation was evaluated by RNA immunoprecipitation, RNA pull-down, and Luciferase gene reporter analysis.PUM2 is upregulated in both cartilage tissue of osteoarthritis patients and IL-1β-stimulated chondrocytes. PUM2 overexpression reduces cell viability and promotes cell apoptosis and ROS generation of chondrocytes. PUM2 silencing increases cell viability and ameliorates cell apoptosis as well as ROS generation in chondrocytes induced by IL-1β. PUM2 inhibits FOXO3 expression via binding its mRNA 3'-UTR. PUM2 forms a signaling axis with FOXO3 in IL-1β induced chondrocyte damage.PUM2 is upregulated in cartilage tissue of osteoarthritis and positively regulates chondrocytes apoptosis through controlling FOXO3 protein expression.© 2024 Published by Elsevier Ltd.