Osteoarthritis (OA) is an extremely common type of chronic progressive disease in clinical practice. lncRNA TUC339 has a close association with bone marrow mesenchymal stem cell (BMSC) and an important impact on organismal inflammation. However, the mechanism of BMSC-derived lncRNA TUC339 on OA was poorly understood. In this study, we found that TUC339 was lower in the research group than in the control group and it was negatively correlated with IL-6, IL-8 and TNF-α. Prognosis TUC339 was lower in patients with recurrent OA than in those without recurrence, and ROC analysis manifested that TUC339 had a better predictive value for recurrence of OA. Phenotypic identification revealed elevated expression of CD29 and CD44 in BMSCs and TSG101, CD63 and CD81 in BMSCs-exosome (BMSCs-exo), with a stem cell versus exosome phenotype. Finally, animal experiments improved significantly in joint injury in the BMSCs-exo and TUC339-overexpression vector groups compared with control groups. Similarly, the activity of chondrocytes was enhanced, and apoptosis was reduced in the BMSCs-exo group versus the TUC339-overexpression vector group of rats. Study demonstrated that BMSCs-exo improves OA by elevating the expression of TUC339 to promote M1-type mø to M2-type polarization, suppressing inflammation and promoting chondrocyte activity, which provides a reliable basis for future transplantation therapy of MSCs for OA.