Objective: Studies have proposed the role of AP-2α in human disease. However, few have focused on its effects on intervertebral disc degeneration (IDD). This study intends to discuss the role of AP-2α in IDD by regulating TGF-β1 and Smad3 expression.
Methods: The AP-2α and TGF-β1 expression in IDD NP clinical samples was detected. Rat models of IDD were established by acupuncture. The rats were injected with AP-2α low expression adeno-associated virus or TGF-β1 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-2α or overexpressed TGF-β1 vector to figure out their functions in growth, senescence and apoptosis.
Results: AP-2α and TGF-β1 were upregulated in NP tissues of patients and rats with IDD. AP-2α silencing limited the activation of TGF-β1 signaling pathway. Reduced AP-2α 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-β1 weakened the effect of down-regulated AP-2α on NP tissues and cells in IDD.
Conclusion: Collectively, our study demonstrates that knockdown of AP-2α restricts TGF-β1 and Smad3 expression to promote proliferation and depress senescence and apoptosis of NP cells in rats with IDD.
Keywords: Activator protein-2α; Intervertebral disc degeneration; Nucleus pulposus cells; Small mothers against decapentaplegic; Transforming growth factor-β signaling pathway.
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