Placenta-Derived Mesenchymal Stem Cell Exosomes Alleviate Osteoarthritis by Suppressing Inflammation, Oxidative Stress, and Cartilage Degeneration

Objective:This study aimed to investigate the therapeutic effects of placenta-derived mesenchymal stem cell exosomes (PMSC-Exos) on osteoarthritis (OA). It also sought to elucidate their anti-inflammatory and chondroprotective mechanisms. Exosomes derived from 293T cells (293T-Exos) were used as a control. Methods:Exosomes were isolated from PMSCs and 293T cells using ultracentrifugation. They were characterized by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blotting for exosomal markers CD9, CD63, and TSG101. Rat chondrocytes were stimulated with IL-1β to establish an OA cell model. This model was then treated with either 293T-Exos or PMSC-Exos. The secretion of TNF-α, IL-6, and IL-1β was measured by ELISA. Apoptosis and reactive oxygen species (ROS) levels were analyzed by flow cytometry. The expression of OA-related proteins (COL2A1, CECR4, MMP13, CASPASE1, TNF-α, ADAMTS5) was detected by Western blotting. In an in vivo OA model, SD rats received intra-articular collagenase to induce OA, followed by exosome treatment into the knee. Joint morphology was evaluated by micro-CT. Results:Both PMSC-Exos and 293T-Exos showed characteristic exosomal morphology, size distribution, and marker expression. However, 293T-Exos had no therapeutic effect. PMSC-Exos significantly reduced TNF-α, IL-6, and IL-1β levels. They also decreased apoptosis and ROS accumulation, and restored cartilage matrix protein expression. Specifically, PMSC-Exos upregulated COL2A1, while downregulating CECR4, MMP13, CASPASE1, TNF-α, and ADAMTS5, in cellular and animal models. In vivo, PMSC-Exos alleviated cartilage erosion, reduced osteophyte formation, and increased cartilage thickness, demonstrating significant joint protection.