TSPAN9 Protects Cartilage Cells from Aging by Recycling Damaged Mitochondria

The progressive degeneration of articular cartilage, a hallmark of osteoarthritis (OA), is significantly driven by chondrocyte senescence (cellular aging). Senescent chondrocytes accumulate in joints, releasing pro-inflammatory factors that further damage cartilage and perpetuate the disease cycle. While the mechanisms leading to chondrocyte senescence are complex, the role of mitochondrial dysfunction is increasingly recognized. This study sought to understand the protective effect and underlying mechanism of TSPAN9-mediated mitocytosis in mitigating interleukin-1β-induced rat chondrocyte senescence.

The study found that IL-1β exposure significantly induced chondrocyte senescence, evidenced by a 3.2-fold increase in p16 expression and a 2.8-fold increase in p21 expression compared to healthy controls. TSPAN9 overexpression remarkably attenuated these markers, reducing p16 levels by 48% and p21 levels by 43% in IL-1β-treated cells. Furthermore, IL-1β caused a 65% reduction in mitochondrial membrane potential and a 2.1-fold increase in reactive oxygen species (ROS), indicating severe mitochondrial dysfunction. > TSPAN9 overexpression significantly restored mitochondrial membrane potential by 75% and decreased ROS levels by 35%, demonstrating a robust protective effect on mitochondrial health. This protective action was attributed to enhanced mitocytosis, a process of selective mitochondrial degradation, with TSPAN9 increasing the colocalization of mitochondria with lysosomes by 2.5-fold.