Fig. 7. Schematic diagram representing the molecular pathway by which SEPHS1 deficiency exacerbates OA development.

SEPHS1 expression is downregulated in OA chondrocytes. SEPHS1 deficiency impairs cellular capacity to synthesize stress-related selenoproteins with oxidoreductase functions in chondrocytes, elevating ROS levels. This event, in turn, enhances DNA damage, cellular senescence, and SASPs expression, causing the catabolic degeneration of the cartilage matrix by fostering chronic inflammation in the joint environments.