Tumor necrosis factor α-mediated cleavage and inactivation of SirT1 in human osteoarthritic chondrocytes.

ABSTRACT:

Objective

The protein deacetylase SirT1 positively regulates cartilage-specific gene expression, while the proinflammatory cytokine tumor necrosis factor α (TNFα) negatively regulates these same genes. This study was undertaken to test the hypothesis that SirT1 is adversely affected by TNFα, resulting in altered gene expression.

Methods

Cartilage-specific gene expression, SirT1 activity, and results of chromatin immunoprecipitation analysis at the α2(I) collagen enhancer site were determined in RNA, protein extracts, and nuclei of human osteoarthritic chondrocytes left untreated or treated with TNFα. Protein extracts from human chondrocytes transfected with epitope-tagged SirT1 that had been left untreated or had been treated with TNFα were analyzed by immunoblotting with Si

SUBMITTER: Dvir-Ginzberg M 

PROVIDER: S-EPMC3174010 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature