Journal
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Volume 23, Issue 8, Pages 5737-5750Publisher
WILEY
DOI: 10.1111/jcmm.14488
Keywords
angiopoietin-like protein 8; extracellular matrix; inflammation; intervertebral disc degeneration; NF-kappa B
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Funding
- National Key Research and Development Program of China [2018YFB1105700]
- National Natural Science Foundation of China [U1603121, 81772401]
- Natural Science Foundation of Hubei Province [WJ2017Z016]
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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-kappa B 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.
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