ArticlePloS one2015
The Sirt1 Activators SRT2183 and SRT3025 Inhibit RANKL-Induced Osteoclastogenesis in Bone Marrow-Derived Macrophages and Down-Regulate Sirt3 in Sirt1 Null Cells.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 36 citations in OpenAlex.
- Metabolic Rewiring and Post-Translational Modifications: Unlocking the Mechanisms of Bone Turnover in Osteoporosis.Aging and disease · 2025Review
- Sirt1: An Increasingly Interesting Molecule with a Potential Role in Bone Metabolism and Osteoporosis.Biomolecules · 2024Review
- Exploring epigenetic strategies for the treatment of osteoporosis.Molecular biology reports · 2024Review
- A Review of Proposed Mechanisms in Rheumatoid Arthritis and Therapeutic Strategies for the Disease.Endocrine, metabolic & immune disorders drug targets · 2024Review
- Bioinformatics Analysis and Experimental Validation of Endoplasmic Reticulum Stress-Related Genes in Osteoporosis.International journal of general medicine · 2024Article
- Oxidative Stress and Natural Antioxidants in Osteoporosis: Novel Preventive and Therapeutic Approaches.Antioxidants (Basel, Switzerland) · 2023Review
- Activation of the sirtuin silent information regulator 1 pathway inhibits pathological myocardial remodeling.Frontiers in pharmacology · 2023Review
- Novel Role of the SIRT1 in Endocrine and Metabolic Diseases.International journal of biological sciences · 2023Review
- Reversing the imbalance in bone homeostasis via sustained release of SIRT-1 agonist to promote bone healing under osteoporotic condition.Bioactive materials · 2023Article
- Sirtuins mediate mitochondrial quality control mechanisms: a novel therapeutic target for osteoporosis.Frontiers in endocrinology · 2023Review
- SRT2183 and SRT1720, but not Resveratrol, Inhibit Osteoclast Formation and Resorption in the Presence or Absence of Sirt1.Journal of bone research · 2023Article
- Regulation of sclerostin by the SIRT1 stabilization pathway in osteocytes.Cell death and differentiation · 2022Article
- Osteonecrosis development by tooth extraction in zoledronate treated mice is inhibited by active vitamin D analogues, anti-inflammatory agents or antibiotics.Scientific reports · 2022Article
- miR-9-5p promotes wear-particle-induced osteoclastogenesis through activation of the SIRT1/NF-κB pathway.3 Biotech · 2021Article
- Tooth extraction in mice administered zoledronate increases inflammatory cytokine levels and promotes osteonecrosis of the jaw.Journal of bone and mineral metabolism · 2021Article
- Article
- Role of Silent Information Regulator 1 (SIRT1) in Regulating Oxidative Stress and Inflammation.Inflammation · 2020Review
- The road ahead for health and lifespan interventions.Ageing research reviews · 2020Review
- Mitochondrial Deacetylase Sirt3 Reduces Vascular Dysfunction and Hypertension While Sirt3 Depletion in Essential Hypertension Is Linked to Vascular Inflammation and Oxidative Stress.Circulation research · 2020Article
- Blueberry Juice Antioxidants Protect Osteogenic Activity against Oxidative Stress and Improve Long-Term Activation of the Mineralization Process in Human Osteoblast-Like SaOS-2 Cells: Involvement of SIRT1.Antioxidants (Basel, Switzerland) · 2020Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Increased osteoclast-mediated bone resorption is characteristic of osteoporosis, malignant bone disease and inflammatory arthritis. Targeted deletion of Sirtuin1 (Sirt1), a key player in aging and metabolism, in osteoclasts results in increased osteoclast-mediated bone resorption in vivo, making it a potential novel therapeutic target to block bone resorption. Sirt1 activating compounds (STACs) were generated and were investigated in animal disease models and in humans however their mechanism of action was a source of controversy. We studied the effect of SRT2183 and SRT3025 on osteoclastogenesis in bone-marrow derived macrophages (BMMs) in vitro, and discovered that these STACs inhibit RANKL-induced osteoclast differentiation, fusion and resorptive capacity without affecting osteoclast survival. SRT2183 and SRT3025 activated AMPK, increased Sirt1 expression and decreased RelA/p65 lysine310 acetylation, critical for NF-κB activation, and an established Sirt1 target. However, inhibition of osteoclastogenesis by these STACs was also observed in BMMs derived from sirt1 knock out (sirt1-/-) mice lacking the Sirt1 protein, in which neither AMPK nor RelA/p65 lysine 310 acetylation was affected, confirming that these effects require Sirt1, but suggesting that Sirt1 is not essential for inhibition of osteoclastogenesis by these STACs under these conditions. In sirt1 null osteoclasts treated with SRT2183 or SRT3025 Sirt3 was found to be down-regulated. Our findings suggest that SRT2183 and SRT3025 activate Sirt1 and inhibit RANKL-induced osteoclastogenesis in vitro however under conditions of Sirt1 deficiency can affect Sirt3. As aging is associated with reduced Sirt1 level and activity, the influence of STACs on Sirt3 needs to be investigated in vivo in animal and human disease models of aging and osteoporosis.
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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.