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Sirtuin 6 prevents matrix degradation through inhibition of the NF-κB pathway in intervertebral disc degeneration.
- Source :
-
Experimental cell research [Exp Cell Res] 2017 Mar 15; Vol. 352 (2), pp. 322-332. Date of Electronic Publication: 2017 Feb 16. - Publication Year :
- 2017
-
Abstract
- Intervertebral disc degeneration (IDD) is marked by imbalanced metabolism of the extracellular matrix (ECM) in the nucleus pulposus (NP) of intervertebral discs. This study aimed to determine whether sirtuin 6 (SIRT6), a member of the sirtuin family of nicotinamide adenine dinucleotide-dependent deacetylases, protects the NP from ECM degradation in IDD. Our study showed that expression of SIRT6 markedly decreased during IDD progression. Overexpression of wild-type SIRT6, but not a catalytically inactive mutant, prevented IL-1β-induced NP ECM degradation. SIRT6 depletion by RNA interference in NP cells caused ECM degradation. Moreover, SIRT6 physically interacted with nuclear factor-κB (NF-κB) catalytic subunit p65, transcriptional activity of which was significantly suppressed by SIRT6 overexpression. These results suggest that SIRT6 prevented NP ECM degradation in vitro via inhibiting NF-κB-dependent transcriptional activity and that this effect depended on its deacetylase activity.<br /> (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Subjects :
- Adolescent
Adult
Aged
Case-Control Studies
Cells, Cultured
Female
Humans
Intervertebral Disc Degeneration pathology
Male
Middle Aged
Nucleus Pulposus metabolism
Nucleus Pulposus pathology
Protein Binding
Signal Transduction
Sirtuins genetics
Extracellular Matrix metabolism
Intervertebral Disc Degeneration metabolism
NF-kappa B metabolism
Sirtuins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2422
- Volume :
- 352
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Experimental cell research
- Publication Type :
- Academic Journal
- Accession number :
- 28215636
- Full Text :
- https://doi.org/10.1016/j.yexcr.2017.02.023