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

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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 ANG2gene 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, 10samples with gradesII andIII IDD were categorized as the mild IDD group; for comparison, another 10specimens with gradesIV andV 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 collagenII 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.