FoxO1a mediated cadmium-induced annulus fibrosus cells apoptosis contributes to intervertebral disc degeneration in smoking

Cadmium (Cd), a type of heavy metal that accumulates in the body because of smoking, mediates the toxic effect of smoking in many diseases, such as Cardiovascular Disease, osteoarthritis, and osteoporosis. However, the toxic effect of Cd on intervertebral disc tissues have not been reported. In the current study, we demonstrated that Cd induced the Apoptosis of annulus fibrosus (AF) cells, which contributed to intervertebral disc degeneration (IVDD). Specifically, Cd induced the nuclear translocation of FoxO1a, which drives AF cells Apoptosis through mitochondrial-related pathway. Phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signal pathway is also involved in this process. The combined use of LY29002, an inhibitor of PI3K, and small interfering RNA-targeting FoxO1a confirmed the relationship between the PI3K/Akt signal pathway and FoxO1a. In summary, present research explores the mechanism behind the contribution of smoking to IVDD and finds a new feasible target for preventing IVDD in smoking.