ArticleAnnals of the rheumatic diseases2022
Digoxin targets low density lipoprotein receptor-related protein 4 and protects against osteoarthritis.
Article in Annals of the rheumatic diseases, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- A systematic review of clinical and preclinical evidences for Janus kinase inhibitors in large vessel vasculitis.Clinical rheumatology · 2022Pooled it
- Digoxin Alleviates Osteoarthritis by Inhibiting Macrophage Extracellular Trap Formation via Disruption of the LSP1-SOD1 Interaction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- High-throughput screening identifies FDA approved drug mitiglinide as a novel pyroptosis inhibitor and therapeutic agent for osteoarthritis.Journal of advanced research · 2026Article
- WTAP-Mediated mAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Dapagliflozin regulates chondrocyte homeostasis and protects against osteoarthritis via targets AMPKα and SGLT2.Cell death discovery · 2026Article
- Irisin inhibits adipogenic differentiation of bone marrow mesenchymal stem cells through the SIRT1/RANBP2/FTO signaling axis and protects against osteoporosis.Cell death discovery · 2026Article
- Dabigatran Attenuates Osteoporosis by Balancing Osteoblastogenesis and Osteoclastogenesis by Targeting PRKAB1 and RELA.Research (Washington, D.C.) · 2026Article
- KIAA1429-mediated MCellular & molecular biology letters · 2025Article
- Fexofenadine protects against osteoarthritis by targeting Smad2 and STAT1 to enhance anabolism and binding cPLA2 to inhibit catabolism.Cell death discovery · 2025Article
- Panaxatriol exerts anti-senescence effects and alleviates osteoarthritis and cartilage repair fibrosis by targeting UFL1.Journal of advanced research · 2025Article
- Genetically engineered chondrocyte-mimetic nanoplatform attenuates osteoarthritis by blocking IL-1β and restoring sirtuin-3.Science advances · 2025Article
- Inhibition of Heat Shock Protein 90β by Catalpol: A Potential Therapeutic Approach for Alleviating Inflammation-Induced Cartilage Injuries in Osteoarthritis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Cardiac Glycosides: From Natural Defense Molecules to Emerging Therapeutic Agents.Biomolecules · 2025Review
- AIDS patients suffer higher risk of advanced knee osteoarthritis progression due to lopinavir-induced Zmpste24 inhibition.Bone research · 2025Article
- Postoperative Weight Loss After Antiobesity Medications and Revision Risk After Joint Replacement.JAMA network open · 2025Article
- LRP4 and Agrin Are Modulated by Cartilage Degeneration and Involved in β-Catenin Signaling in Human Articular Chondrocytes.International journal of molecular sciences · 2025Article
- The potential of mitochondrial transfer as the modifying therapy for osteoarthritis.Frontiers in cell and developmental biology · 2025Review
- Transcriptome Combined with Mendelian Randomization to Identify and Validate Biomarkers Associated with Parthanatos in Sepsis.Journal of inflammation research · 2025Article
- 4-Octyl itaconate inhibits synovitis in the mouse model of post-traumatic osteoarthritis and alleviates pain.Chinese journal of traumatology = Zhonghua chuang shang za zhi · 2025Article
- Therapeutic role of aripiprazole in cartilage defects explored through a drug repurposing approach.Scientific reports · 2024Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
objectivesDysregulated chondrocyte metabolism is closely associated with the pathogenesis of osteoarthritis (OA). Suppressing chondrocyte catabolism to restore cartilage homeostasis has been extensively explored, whereas far less effort has been invested toward enhancing chondrocyte anabolism. This study aimed to repurpose clinically approved drugs as potential stimulators of chondrocyte anabolism in treating OA.
methodsScreening of a Food and Drug Administration-approved drug library; Assays for examining the chondroprotective effects of digoxin in vitro; Assays for defining the therapeutic effects of digoxin using a surgically-induced OA model; A propensity-score matched cohort study using The Health Improvement Network to examine the relationship between digoxin use and the risk of joint OA-associated replacement among patients with atrial fibrillation; identification and characterisation of the binding of digoxin to low-density lipoprotein receptor-related protein 4 (LRP4); various assays, including use of CRISPR-Cas9 genome editing to delete LRP4 in human chondrocytes, for examining the dependence on LRP4 of digoxin regulation of chondrocytes.
resultsSerial screenings led to the identification of ouabain and digoxin as stimulators of chondrocyte differentiation and anabolism. Ouabain and digoxin protected against OA and relieved OA-associated pain. The cohort study of 56 794 patients revealed that digoxin use was associated with reduced risk of OA-associated joint replacement. LRP4 was isolated as a novel target of digoxin, and deletion of LRP4 abolished digoxin's regulations of chondrocytes.
conclusionsThese findings not only provide new insights into the understanding of digoxin's chondroprotective action and underlying mechanisms, but also present new evidence for repurposing digoxin for OA.
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Registered trials
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