ArticleCell death & disease2019
Evidence of necroptosis in osteoarthritic disease: investigation of blunt mechanical impact as possible trigger in regulated necrosis.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 79 citations in OpenAlex.
- Nucleic Acids as Emerging Regulators of Calcium Phosphate Biomineralization.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- DJ-1 promotes necroptosis of chondrocytes by the PTEN/PI3K-AKT signaling pathway.Cellular and molecular life sciences : CMLS · 2026Article
- Programmed cell death in osteoarthritis.Apoptosis : an international journal on programmed cell death · 2026Review
- Mitochondrial quality control modulating chondrocyte behavior and fate in knee osteoarthritis: mechanistic insights and therapeutic prospects.Frontiers in immunology · 2026Review
- Integrative multi-omics identifiesFrontiers in immunology · 2026Article
- USP39 inhibits MLKL phosphorylation and deubiquitination to suppress necroptosis of nucleus pulposus cells and attenuate intervertebral disc degeneration.Journal of orthopaedic translation · 2026Article
- Metabolic reprogramming in intervertebral disc degeneration: mechanisms and therapeutic opportunities.Frontiers in cell and developmental biology · 2026Review
- Regulated Cell Death Pathways in Chondrocytes During Septic Arthritis: Current Evidence and Future Perspectives.Journal of inflammation research · 2026Review
- Targeting the CXCL12/CXCR4 pathway by an optimized derivative or EPI-X4 preserves chondrocyte function and offers a novel therapeutic approach in rheumatic diseases.Arthritis research & therapy · 2025Article
- Growth/Differentiation Factor 15 Promotes a Pro-Regenerative Response in Chondrocytes Upon Cartilage Injury.MedComm · 2025Article
- Porous PLGA microspheres loaded with PTHJournal of orthopaedic translation · 2025Article
- GDF11 protects against mitochondrial-dysfunction-dependent NLRP3 inflammasome activation to attenuate osteoarthritis.Journal of advanced research · 2025Article
- Osteocyte necroptosis drives osteoclastogenesis and alveolar bone resorption during orthodontic tooth movement.Scientific reports · 2025Article
- Acetyl-11-keto-beta-boswellic acid ameliorates monosodium iodoacetate-induced osteoarthritis in rats: implications of HMGB1/TLR4/NF-κB and Nrf2/HO-1.Frontiers in pharmacology · 2025Article
- Exploration and breakthrough in the mode of intervertebral disc cell death may lead to significant advances in treatments for intervertebral disc degeneration.Journal of orthopaedic surgery and research · 2024Review
- Omega-3 fatty acids protect cartilage from acute injurie by reducing the mechanical sensitivity of chondrocytes.Journal of orthopaedic surgery and research · 2024Article
- Significance of Necroptosis in Cartilage Degeneration.Biomolecules · 2024Review
- Screening chondrocyte necroptosis-related genes in the diagnosis and treatment of osteoarthritis.Heliyon · 2024Article
- Bioactive fiber-reinforced hydrogel to tailor cell microenvironment for structural and functional regeneration of myotendinous junction.Science advances · 2024Article
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Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Joint injuries are highly associated with cell death and development of posttraumatic osteoarthritis (PTOA). The present study focused on necroptosis as a possible modality of chondrocyte death after cartilage trauma and its relevance in OA disease in general. For this purpose, apoptosis- and necroptosis-associated markers were determined in highly degenerated (ICRS ≥ 3) as well as macroscopically intact cartilage tissue (ICRS ≤ 1) by means of real-time PCR and immunohistochemistry (IHC). Moreover, influence of blunt trauma and/or stimulation with cycloheximide (CHX), TNF-a, and caspase-inhibitor zVAD were investigated in cartilage explants (ICRS ≤ 1). Further characterization of necroptosis was performed in isolated chondrocytes. We found that gene expression levels of RIPK3 (4.2-fold, P < 0.0001) and MLKL (2.7-fold, P < 0.0001) were elevated in highly degenerated cartilage tissue, which was confirmed by IHC staining. After ex vivo trauma and/or CHX/TNF stimulation, addition of zVAD further enhanced expression of necroptosis-related markers as well as release of PGE2 and nitric oxide, which was in line with increased cell death and subsequent release of intracellular HMGB1 and dsDNA in CHX/TNF stimulated chondrocytes. However, trauma and/or chemically induced cell death and subsequent release of pro-inflammatory mediators could be largely attenuated by RIPK1-inhibitor necrostatin 1 or antioxidant N-acetylcysteine. Overall, the study provided clear evidence of necroptotic cell death in OA disease. Moreover, a possible link between cartilage injury and necroptotic processes was found, depending on oxidative stress and cytokine release. These results contribute to further understanding of cell death in PTOA and development of novel therapeutic approaches.
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