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

Abstract:

: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.

journal_name

Int J Mol Med

authors

Wang K,Kang L,Liu W,Song Y,Wu X,Zhang Y,Hua W,Zhao K,Li S,Tu J,Luo R,Yang C

doi

10.3892/ijmm.2018.3576

subject

Has Abstract

pub_date

2018-06-01 00:00:00

pages

3551-3558

issue

6

eissn

1107-3756

issn

1791-244X

journal_volume

41

pub_type

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