Open AccessAngiopoietin‐like protein 8 expression and association with extracellular matrix metabolism and inflammation during intervertebral disc degeneration
Author(s) -
Liao Zhiwei,
Wu Xinghuo,
Song Yu,
Luo Rongjin,
Yin Huipeng,
Zhan Shengfeng,
Li Shuai,
Wang Kun,
Zhang Yukun,
Yang Cao
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.14488
Subject(s) - extracellular matrix , inflammation , mmp3 , matrix metalloproteinase , cartilage , intervertebral disc , catabolism , anabolism , gene knockdown , biology , microbiology and biotechnology , medicine , pathology , gene expression , immunology , metabolism , apoptosis , anatomy , endocrinology , gene , biochemistry
Intervertebral disc degeneration (IDD) is considered the primary culprit for low back pain. Although the underlying mechanisms remain unknown, hyperactive catabolism of the extracellular matrix (ECM) and inflammation are suggested to play critical roles in IDD progression. This study was designed to elucidate the role of angiopoietin‐like protein 8 (ANGPTL8) in the progression of IDD, especially the relationship of ANGPTL8 with ECM metabolism and inflammation. A positive association between ANGPTL8 expression and degenerative grades of IDD was detected in the analysis of human nucleus pulposus tissue samples. Silencing of ANGPTL8 attenuated the degradation of the anabolic protein type collagen II, and reduced the expression of the catabolic proteins MMP3 and MMP9, and the inflammatory cytokine IL‐6 through inhibition of NF‐κB signalling activation. In addition, the effect of ANGPTL8 was evaluated in a rat model of puncture‐induced IDD. Based on the imaging results and histological examination in animal study, knockdown of ANGPTL8 was demonstrated to ameliorate the IDD progression. These results demonstrate the detrimental role of ANGPTL8 expression in the pathogenesis of IDD and may provide a new therapeutic target for IDD treatment.