While OPN retarded osteoarthritis progression through the OPN/CD44/PI3K signaling,26 inhibiting the PI3K/AKT pathway could suppress cartilage degeneration and subchondral bone remodeling in osteoarthritis.25 Similarly, two research groups have reached opposite conclusions regarding the role of OPN in IDD. This evidence concerns the gene SPP1 and intervertebral disk degenerative disorder.