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

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

doi:10.3892/ijmm.2018.3576

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

Authors:
- Kun Wang
- Liang Kang
- Wei Liu
- Yu Song
- Xinghuo Wu
- Yukun Zhang
- Wenbin Hua
- Kangcheng Zhao
- Shuai Li
- Ji Tu
- Rongjin Luo
- Cao Yang
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Affiliations: Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China, Department of Orthopedics, First Hospital of Wuhan, Wuhan 430022, China
Published online on: March 19, 2018 https://doi.org/10.3892/ijmm.2018.3576
Pages: 3551-3558

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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.

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