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

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-κB (NF-κB) 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-κB signaling pathway. Elevated Ang-2 levels also increased interleukin-1β 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.