Sirtuin 2 Promotes Collagen II Synthesis Through Deacetylating p65-NF-κB in Human Intervertebral Disc Cartilage Endplate Cells

Abstract

Backgrounds: Intervertebral disc degeneration (IDD) is a major cause of low back pain, however its underlying pathogenesis is complicated and remains extensively illumination. Here we investigate the role of sirtuin 2 (SIRT2) in human IDD. Methods: We compared the RNA and protein levels of SIRT2 in non-degenerate and degenerate human tissues and assessed their relationship with clinical features. After isolated the intervertebral disc cartilage endplate (CEP) cells, the cell proliferation and apoptosis were tested. Further underlying mechanisms were explored from molecular levels. Findings: We found that the CEP cell proliferation and apoptosis was not changed during IDD. However, the CEP collagen synthesis and secretion were attenuated in IDD patients compared with healthy individuals. Moreover, the SIRT2 expression was downregulated in the CEP cells isolated from IDD patients. Overexpressing SIRT2 can significantly rescue the capacity of collagen II synthesis. Upon SIRT2 overexpression, the NF-κB was deacetylated and subsequently modulate collagen gene transcription, therefore preventing IDD development. Interpretation: SIRT2 downregulation is one of the possible causes of IDD during aging. Overexpressing SIRT2 will attenuate IDD progression via deactivating NFκB. Funding Statement: This work is supported by the National Natural Science Foundation of China (NSFC #81601957) Declaration of Interests: The authors state: None declared. Ethics Approval Statement: The work was approved by the Ethics Committee of the China–Japan Union Hospital (Changchun, China). Written informed consent was obtained from patients or relatives before tissue collection. All procedures are complied with the principles outlined in the Declaration of Helsinki.