Role of AP-2 alpha/TGF-beta 1/Smad3 axis in rats with intervertebral disc degeneration

Objective: Studies have proposed the role of AP-2 alpha in human disease. However, few have focused on its effects on intervertebral disc degeneration (IDD). This study intends to discuss the role of AP-2 alpha in IDD by regulating TGF-beta 1 and Smad3 expression. Methods: The AP-2 alpha and TGF-beta 1 expression in IDD NP clinical samples was detected. Rat models of IDD were established by acupuncture. The rats were injected with AP-2 alpha low expression adeno-associated virus or TGF-beta 1 high expression adeno-associated virus to observe their effects on pathological damages, NP cell apoptosis, matrix metalloproteinase-2 (MMP-2), MMP-9, Smad3, Aggrecan and collagen (Col)-2 expression in NP tissues. The NP cells were isolated and transfected with silenced AP-2 alpha or overexpressed TGF-beta 1 vector to figure out their functions in growth, senescence and apoptosis. Results: AP-2 alpha and TGF-beta 1 were upregulated in NP tissues of patients and rats with IDD. AP-2 alpha silencing limited the activation of TGF-beta 1 signaling pathway. Reduced AP-2 alpha ameliorated pathological changes, declined MMP-2, MMP-9 and Smad3 expression and elevated Aggrecan and Col-2 expression in NP tissues of rats with IDD, and speeded up the growth and depressed senescence and apoptosis of NP cells of rats with IDD. Up-regulating TGF beta 1 weakened the effect of down-regulated AP-2 alpha on NP tissues and cells in IDD. Conclusion: Collectively, our study demonstrates that knockdown of AP-2 alpha restricts TGF-beta 1 and Smad3 expression to promote proliferation and depress senescence and apoptosis of NP cells in rats with IDD.