GDF5 and intervertebral disk degenerative disorder: In addition to the aforementioned mechanisms, annulus fibrosus exposed to both IL-1 and TNF-α resulted in a significant decrease in growth differentiation factor 5 (GDF5) levels, which was found to play an important anabolic role in disc development [28]. Another signal cascade that was noted to be activated in patients with disc degeneration compared to those who had nondegenerated discs was the Notch pathway [28].