Angiopoietin-2 promotes extracellular matrix degradation in human degenerative nucleus pulposus cells

作者：Wang, Kun; Kang, Liang; Liu, Wei; Song, Yu; Wu, Xinghuo; Zhang, Yukun; Hua, Wenbin; Zhao, Kangcheng; Li, Shuai; Tu, Ji; Luo, Rongjin; Yang, Cao^*

来源：International Journal of Molecular Medicine, 2018, 41(6): 3551-3558.

DOI：10.3892/ijmm.2018.3576

• angiopoietin-2
• intervertebral disc
• degenerative nucleus pulposus cells
• intervertebral disc degeneration
• nuclear factor-B

In contrast to healthy intervertebral discs (IVDs), degenerate IVDs become vascularized. Here, we determined the role of an angiogenesis promoter, angiopoietin (Ang)-2, in the pathology of IVD degeneration (IDD). We evaluated degree of IDD using the Pfirrmann grading system. We used quantitative real-time polymerase chain reaction and western blotting to analyze ANG2 gene expression and Ang-2 protein levels, respectively. The involvement of Ang-2 in IVD degradation and regulation of nuclear factor-B (NF-B) signaling was examined by immunohistochemistry, western blotting and immunofluorescence. As a result, 10 samples with grades II and III IDD were categorized as the mild IDD group; for comparison, another 10 specimens with grades IV and V constituted the severe IDD group. Ang-2 expression was significantly higher in severe IDD than in mild IDD. Exogenous Ang-2 administration led to increased production of catabolic proteinases and loss of aggrecan and collagen II in degenerative NP cell cultures, which was mediated by the NF-B signaling pathway. Elevated Ang-2 levels also increased interleukin-1 expression in degenerative NP cells. We conclude that the release of Ang-2 aggravates NP cell degradation and plays an important role in IDD. Ang-2 may thus constitute a novel therapeutic target for the treatment of IVD.

• 出版日期2018-6
• 单位华中科技大学; 武汉市中西医结合医院