For example, uneven loading of a bovine IVD, producing concave and convex sides, primarily stressed the AF in the concave side, leading to decreased AF tissue, increased caspase-3 (CASP3), and reduced ACAN, while in the convex side, MMP1, ADAMTS4, IL1β, and IL6 mRNA was upregulated in the AF but not the NP compared to controls [75]. Here, ACAN is linked to atrial fibrillation.