The present study examined the role of Wnt/β-catenin signaling pathway in the degeneration of nucleus pulposus cells and the protective effect of DKK1 on nucleus pulposus cells.The model of nucleus pulposus cell degeneration was induced by intra-disc injection of TNF-α,and the expression of β-catenin protein was detected by Western blotting.The cultured rabbit nucleus pulposus cells were divided into 4 groups.In group A,the cells were cultured with normal medium and served as control group.In group B,the cells were cultured with TNF-α and acted as degeneration group.In group C,the cells were cultured with TNF-α and transfected with Adv-eGFP and was used as fluorescence control group.In group D,the cells were cultured with TNF-α and transfected with Adv-hDKK1-eGFP,serving as intervention group.The expression of type Ⅱ collagen,proteoglycan,β-catenin,and MMP-13 in each group was detected by immunocytochemistry and RT-PCR.The result showed that TNF-α increased the expression of β-catenin and MMP-13,and significantly inhibited the synthesis of type Ⅱ collagen and proteoglycan,which resulted in the degeneration of nucleus pulposus cells.This effect could be obviously reversed by DKK1.We are led to concluded that TNF-α could activate the Wnt/β-catenin signaling pathway,and increase the expression of MMP-13,thereby resulting in disc degeneration.Specifically blocking Wnt/β-catenin signaling pathway by DKK-1 could protect the normal metabolism of intervertebral disc tissue.The Wnt pathway plays an important role in the progression of the intervertebral disc degeneration.