ArticleCell communication and signaling : CCS2024
IRF1 regulation of ZBP1 links mitochondrial DNA and chondrocyte damage in osteoarthritis.
Article in Cell communication and signaling : CCS, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Mechanical stress-mediated ferritinophagy aggravates cartilage endplate degeneration via a PIEZO1-NCOA4-ZBP1 axis.Autophagy · 2026Article
- ZBP1 in Neuroinflammation and Neurodegeneration: Z-Nucleic-Acid Sensing, RHIM Signalling and Therapeutic Targeting.International journal of molecular sciences · 2026Review
- IRF1-mediated sensing of oxidized mitochondrial DNA drives macrophage PANoptosis in lung ischemia-reperfusion injury.Apoptosis : an international journal on programmed cell death · 2026Article
- DHODH regulates trophoblast fusion via IFITM-reduced plasma membrane fluidity: Implications for hypertensive disorders of pregnancy.iScience · 2026Article
- Melatonin Exerts Chondroprotective Effects Against Osteoarthritis by Promoting PI3K/AKT/FoxO3-Mediated Mitophagy.The Kaohsiung journal of medical sciences · 2026Article
- Targeting WWP1 ameliorates osteoarthritis by suppressing KLF15 ubiquitination to restore mtDNA and mitochondrial function.Molecular genetics and genomics : MGG · 2026Article
- Article
- Upregulated ZBP1 Is Associated with B-Cell Dysregulation in Systemic Lupus Erythematosus.Biomedicines · 2026Article
- Targeting the mitochondrial metabolite-dynamics-MDVs-MitoEVs axis: a new frontier in osteoarthritis management.Journal of translational medicine · 2026Review
- High Mobility Group Protein B1 Promotes Interferon Regulatory Factor 1 SUMOylation to Prime Trained Immunity of Circulating Monocytes and Aggravate the Progressive Synovial Inflammation in Knee Osteoarthritis.Research (Washington, D.C.) · 2026Article
- Traditional Chinese medicine-derived monomers protect chondrocytes and delay osteoarthritis progression by regulating mitochondrial quality control.Frontiers in molecular biosciences · 2026Review
- Lactate-driven lactylation reprograms chondrocyte fate and joint inflammation in osteoarthritis: linking metabolism with epigenetic regulation.Frontiers in cell and developmental biology · 2026Review
- NF-κB signaling in osteoarthritis: integrating mechanical stress, innate immunity, and cartilage degeneration.Frontiers in immunology · 2026Review
- Mitochondrial-targeted therapy for osteoarthritis: Challenges and opportunities from basic research to clinical translation.Frontiers in immunology · 2026Review
- Molecular mediators of motion: RNA-RBP networks in exercise-induced osteoarthritis protection.Frontiers in genetics · 2026Review
- Bioinformatics and machine learning approaches to explore the biomarkers in fatty acid degradation linked to osteoarthritis.Frontiers in immunology · 2026Article
- Highly Alkaline-ResistantMicroorganisms · 2025Article
- Liver injury severity determines skeletal deterioration: a shared pathophysiological axis between MASLD and osteoarthritis.GeroScience · 2025Article
- CircPAFAH1B2 induces chondrocytes mitochondrial dysfunction and promotes cartilage degeneration through binding molecular chaperone ClpB.Journal of advanced research · 2025Article
- Integrated bioinformatics and network pharmacology to identify and validate macrophage polarization related hub genes in the treatment of osteoarthritis with Astragalus membranaceus.Journal of orthopaedic surgery and research · 2025Article
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Authors and funding
13 authors.
Funding
Abstract
backgroundZ-DNA binding protein 1 (ZBP1) is a nucleic acid sensor that is involved in multiple inflammatory diseases, but whether and how it contributes to osteoarthritis (OA) are unclear.
methodsCartilage tissues were harvested from patients with OA and a murine model of OA to evaluate ZBP1 expression. Subsequently, the functional role and mechanism of ZBP1 were examined in primary chondrocytes, and the role of ZBP1 in OA was explored in mouse models.
resultsWe showed the upregulation of ZBP1 in articular cartilage originating from OA patients and mice with OA after destabilization of the medial meniscus (DMM) surgery. Specifically, knockdown of ZBP1 alleviated chondrocyte damage and protected mice from DMM-induced OA. Mechanistically, tumor necrosis factor alpha induced ZBP1 overexpression in an interferon regulatory factor 1 (IRF1)-dependent manner and elicited the activation of ZBP1 via mitochondrial DNA (mtDNA) release and ZBP1 binding. The upregulated and activated ZBP1 could interact with receptor-interacting protein kinase 1 and activate the transforming growth factor-beta-activated kinase 1-NF-κB signaling pathway, which led to chondrocyte inflammation and extracellular matrix degradation. Moreover, inhibition of the mtDNA-IRF1-ZBP1 axis with Cyclosporine A, a blocker of mtDNA release, could delay the progression of DMM-induced OA.
conclusionsOur data revealed the pathological role of the mtDNA-IRF1-ZBP1 axis in OA chondrocytes, suggesting that inhibition of this axis could be a viable therapeutic approach for OA.
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