ArticleArthritis and rheumatism2012
75-kd sirtuin 1 blocks tumor necrosis factor α-mediated apoptosis in human osteoarthritic chondrocytes.
Article in Arthritis and rheumatism, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 76 citations in OpenAlex.
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- Exploring mitochondrial functions and dysfunctions in chondrocytes: toward the identification of novel therapies for osteoarthritis.Bone research · 2026Review
- Early Administration of N-Acetylcysteine Provides Renal and Cardiac Mitochondrial and Redox Protection, Preventing the Development of Cardio-Renal Syndrome Type IV Induced by 5/6NX.Antioxidants (Basel, Switzerland) · 2025Article
- Two-year post-distraction cartilage-related structural improvement is accompanied by increased serum full-length SIRT1.Arthritis research & therapy · 2024Article
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- Transcriptomic analyses of joint tissues during osteoarthritis development in a rat model reveal dysregulated mechanotransduction and extracellular matrix pathways.Osteoarthritis and cartilage · 2023Article
- The epigenetic players and the chromatin marks involved in the articular cartilage during osteoarthritis.Frontiers in physiology · 2023Review
- Overview of Anti-Inflammatory and Anti-Nociceptive Effects of Polyphenols to Halt Osteoarthritis: From Preclinical Studies to New Clinical Insights.International journal of molecular sciences · 2022Review
- Ginsenoside Rg3 Attenuates TNF-α-Induced Damage in Chondrocytes through Regulating SIRT1-Mediated Anti-Apoptotic and Anti-Inflammatory Mechanisms.Antioxidants (Basel, Switzerland) · 2021Article
- Low-Frequency Vibration Promotes Tumor Necrosis Factor-α Production to Increase Cartilage Degeneration in Knee Osteoarthritis.Cartilage · 2021Article
- The selective degradation of sirtuins via macroautophagy in the MPPCell death discovery · 2021Article
- Knee Osteoarthritis Progression Is Delayed in Silent Information Regulator 2 Ortholog 1 Knock-in Mice.International journal of molecular sciences · 2021Article
- Adaptive responses to air pollution in human dermal fibroblasts and their potential roles in aging.FASEB bioAdvances · 2021Article
- Lysosomal dysfunction in osteoarthritis and aged cartilage triggers apoptosis in chondrocytes through BAX mediated release of Cytochrome c.Osteoarthritis and cartilage · 2021Article
- Serum NT/CT SIRT1 ratio reflects early osteoarthritis and chondrosenescence.Annals of the rheumatic diseases · 2020Article
- CMH-Small Molecule Docks into SIRT1, Elicits Human IPF-Lung Fibroblast Cell Death, Inhibits Ku70-deacetylation, FLIP and Experimental Pulmonary Fibrosis.Biomolecules · 2020Article
- Relevance of SIRT1-NF-κB Axis as Therapeutic Target to Ameliorate Inflammation in Liver Disease.International journal of molecular sciences · 2020Review
- SIRT1 directly activates autophagy in human chondrocytes.Cell death discovery · 2020Article
- Cytoplasmic SIRT1 inhibits cell migration and invasion by impeding epithelial-mesenchymal transition in ovarian carcinoma.Molecular and cellular biochemistry · 2019Article
- Sirtuin 1 Regulates Mitochondrial Biogenesis and Provides an Endogenous Neuroprotective Mechanism Against Seizure-Induced Neuronal Cell Death in the Hippocampus Following Status Epilepticus.International journal of molecular sciences · 2019Article
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9 authors at 1 institution in 1 country.
Funding
Abstract
objectiveSirtuin 1 (SirT1) has been implicated in the regulation of human cartilage homeostasis and chondrocyte survival. Exposing human osteoarthritic (OA) chondrocytes to tumor necrosis factor α (TNFα) generates a stable and enzymatically inactive 75-kd form of SirT1 (75SirT1) via cathepsin B-mediated cleavage. Because 75SirT1 is resistant to further degradation, we hypothesized that it has a distinct role in OA, and the present study was undertaken to identify this role.
methodsThe presence of cathepsin B and 75SirT in OA and normal human chondrocytes was analyzed. Confocal imaging of SirT1 was used to monitor its subcellular trafficking following TNFα stimulation. Coimmunofluorescence staining for cathepsin B, mitochondrial cytochrome oxidase subunit IV, and lysosome-associated membrane protein 1 together with SirT1 was performed. Human chondrocytes were tested for apoptosis by fluorescence-activated cell sorter analysis and immunoblotting for caspases 3 and 8. Human chondrocyte mitochondrial extracts were obtained and analyzed for 75SirT1-cytochrome c association.
resultsConfocal imaging and immunoblot analyses following TNFα challenge of human chondrocytes demonstrated that 75SirT1 was exported to the cytoplasm and colocalized with the mitochondrial membrane. Consistent with this, immunoprecipitation and immunoblot analyses revealed that 75SirT1 is enriched in mitochondrial extracts and associates with cytochrome c following TNFα stimulation. Preventing nuclear export of 75SirT1 or reducing levels of full-length SirT1 and 75SirT1 augmented chondrocyte apoptosis in the presence of TNFα. Levels of cathepsin B and 75SirT1 were elevated in OA versus normal chondrocytes. Additional analyses showed that human chondrocytes exposed to OA-derived synovial fluid generated the 75SirT1 fragment.
conclusionThese data suggest that 75SirT1 promotes chondrocyte survival following exposure to proinflammatory cytokines.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.