ArticleArthritis research & therapy2015
Histone deacetylase inhibition activates Nrf2 and protects against osteoarthritis.
Article in Arthritis research & therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 1 of them a synthesis that pooled it.
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Who cites it
91 citing papers in PubMed, 1 synthesis or guideline pooled it, 174 citations in OpenAlex.
- Systematic review and meta-analysis of experimental studies evaluating the organ protective effects of histone deacetylase inhibitors.Translational research : the journal of laboratory and clinical medicine · 2019Pooled it
- Three-Month Administration of PB125 Modifies Histopathology, Redox Homeostasis, and Mobility in the Hartley Guinea Pig Model of Primary Osteoarthritis.Antioxidants (Basel, Switzerland) · 2026Article
- NF-κB signaling in osteoarthritis: integrating mechanical stress, innate immunity, and cartilage degeneration.Frontiers in immunology · 2026Review
- Transcutaneous carbon dioxide improves joint inflammation and articular cartilage degeneration in rat osteoarthritis models.Bone & joint research · 2025Article
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- Epigenetic Mechanisms Governing Nrf2 Expression and Its Role in Ferroptosis.Biomedicines · 2025Review
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- A ketogenic diet regulates microglial activation to treat drug addiction.Frontiers in pharmacology · 2025Review
- Advanced nanoparticles for osteoarthritis: a review.Frontiers in medicine · 2025Review
- Injectable exosome-reinforced konjac glucomannan composite hydrogel for repairing cartilage defect: activation of endogenous antioxidant pathways.Regenerative biomaterials · 2025Article
- Bone Mesenchymal Stromal Cell-Derived Extracellular Vesicles Protect Articular Cartilage Through Regulating tRF-Gln-TTG-019/UBL3.Mediators of inflammation · 2025Article
- Spinosin ameliorates osteoarthritis through enhancing the Nrf2/HO-1 signaling pathway.European journal of histochemistry : EJH · 2024Article
- Cartilage-inspired self-assembly glycopeptide hydrogels for cartilage regeneration via ROS scavenging.Bioactive materials · 2024Article
- DNA Methylation-Mediated GPX4 Transcriptional Repression and Osteoblast Ferroptosis Promote Titanium Particle-Induced Osteolysis.Research (Washington, D.C.) · 2024Article
- NaNature · 2024Article
- Intra-articular Histone Deacetylase Inhibitor Microcarrier Delivery to Reduce Osteoarthritis.Nano letters · 2023Article
- Tanshinone IIA Facilitates Efficient Cartilage Regeneration under Inflammatory Factors Caused Stress via Upregulating LncRNA NEAT1_2.Biomedicines · 2023Article
- Oxidative stress as a key modulator of cell fate decision in osteoarthritis and osteoporosis: a narrative review.Cellular & molecular biology letters · 2023Review
- Age and oxidative stress regulate Nrf2 homeostasis in human articular chondrocytes.Osteoarthritis and cartilage · 2023Article
- Duality of Valproic Acid Effects on Inflammation, Oxidative Stress and Autophagy in Human Eosinophilic Cells.International journal of molecular sciences · 2023Article
31 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionOsteoarthritis (OA) is a common joint disease that can cause gradual disability among the aging population. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a key transcription factor that regulates the expression of phase II antioxidant enzymes that provide protection against oxidative stress and tissue damage. The use of histone deacetylase inhibitors (HDACi) has emerged as a potential therapeutic strategy for various diseases. They have displayed chondroprotective effects in various animal models of arthritis. Previous studies have established that Nrf2 acetylation enhances Nrf2 functions. Here we explore the role of Nrf2 in the development of OA and the involvement of Nrf2 acetylation in HDACi protection of OA.
methodsTwo OA models-monosodium iodoacetate (MIA) articular injection and destabilization of the medial meniscus (DMM)-were used with wild-type (WT) and Nrf2-knockout (Nrf2-KO) mice to demonstrate the role of Nrf2 in OA progression. A pan-HDACi, trichostatin A (TSA), was administered to examine the effectiveness of HDACi on protection from cartilage damage. The histological sections were scored. The expression of OA-associated matrix metalloproteinases (MMPs) 1, 3, and 13 and proinflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 were assayed. The effectiveness of HDACi on OA protection was compared between WT and Nrf2-KO mice.
resultsNrf2-KO mice displayed more severe cartilage damage in both the MIA and DMM models. TSA promoted the induction of Nrf2 downstream proteins in SW1353 chondrosarcoma cells and in mouse joint tissues. TSA also reduced the expression of OA-associated proteins MMP1, MMP3, and MMP13 and proinflammatory cytokines TNF-α, IL-1β, and IL-6. TSA markedly reduced the cartilage damage in both OA models but offered no significant protection in Nrf2-KO mice.
conclusionsNrf2 has a major chondroprotective role in progression of OA and is a critical molecule in HDACi-mediated OA protection.
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