Targeting Cell Death: Pyroptosis, Ferroptosis, Apoptosis and Necroptosis in Osteoarthritis

Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 9

Published: Jan. 18, 2022

New research has shown that the development of osteoarthritis (OA) is regulated by different mechanisms cell death and types cytokines. Therefore, elucidating mechanism action among various cytokines, processes OA important towards better understanding pathogenesis progression disease. This paper reviews in relation to cytokine-triggered death. We describe morphological features molecular pyroptosis, apoptosis, necroptosis, ferroptosis, summarize current findings defining between OA.

Language: Английский

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D‐mannose alleviates osteoarthritis progression by inhibiting chondrocyte ferroptosis in a HIF‐2α‐dependent manner

Cell Proliferation, Journal Year: 2021, Volume and Issue: 54(11)

Published: Sept. 25, 2021

Abstract Objectives Chondrocyte ferroptosis contributes to osteoarthritis (OA) progression, and D‐mannose shows therapeutic value in many inflammatory conditions. Here, we investigated whether interferes chondrocyte ferroptotic cell death during osteoarthritic cartilage degeneration. Materials methods In vivo anterior cruciate ligament transection (ACLT)‐induced OA mouse model an vitro study of chondrocytes microenvironment induced by interleukin‐1β (IL‐1β) exposure were employed. Combined with Epas1 gene gain‐ loss‐of‐function, histology, immunofluorescence, quantitative RT‐PCR, Western blot, viability flow cytometry experiments performed evaluate the chondroprotective effects progression role hypoxia‐inducible factor 2 alpha (HIF‐2 α) D‐mannose‐induced resistance chondrocytes. Results exerted a effect attenuating sensitivity alleviated progression. HIF‐2α was identified as central mediator Furthermore, overexpression Ad‐ intra‐articular injection abolished eliminated suppressor. Conclusions alleviates suppressing HIF‐2α‐mediated ferroptosis, indicating be potential strategy for ferroptosis‐related diseases.

Language: Английский

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Biochanin A protects against iron overload associated knee osteoarthritis via regulating iron levels and NRF2/System xc-/GPX4 axis

Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 157, P. 113915 - 113915

Published: Nov. 12, 2022

Iron homeostasis plays a positive role in articular cartilage health. Excessive iron or overload can induce oxidative stress damage chondrocytes and ferroptosis cell death, advancing knee osteoarthritis (KOA). However, up to date, few effective agents treat overload-induced KOA (IOKOA). Chinese herbal medicine (CHM) provides abundant resources for drug selection manage bone metabolic conditions, including osteoporosis. Biochanin A (BCA) is novel bioactive multifunctional natural compound isolated from Huangqi, which has protective effects on loss. Nevertheless, the function mechanism of BCA treating IOKOA are still elusive.This study seeks uncover potential therapeutic targets mechanisms management with accumulation.Iron dextrin (500 mg/kg) was intraperitoneally injected into mice establish overloaded model. OA induced through surgery, progression evaluated eight weeks following surgery. severity micro-CT Safranin-O/Fast green staining vivo. deposition joint synovium assessed using Perl's Prussian blue staining. Ferric ammonium citrate (FAC) then administered primary evaluate regulators mediated homeostasis. Toluidine utilized identify vitro. The vitality cells CCK-8 test. apoptosis rate measured Annexin V-FITC/PI assay. intracellular level detected utilizing calcein-AM Reactive oxygen species (ROS), lipid-ROS, mitochondrial membrane potentiality were reflected via fluorescence density. Utilizing RT-qPCR western blotting, expression determined.Micro-CT histological joints showed greater degradation higher buildup iron-overloaded mice. reduce KOA. assay indicated that could rescue killed by iron. Cell rates increased due but improved BCA. Further, content iron, ROS, lipid-ROS ferric treatment restored after different concentrations JC-1 revealed overload.Iron shown promote chondrocyte vivo Moreover, suppressed collagen II MMP catalyzing ROS generation dysfunction. Our results directly concentration inhibiting TfR1 promoting FPN also target Nrf2/system xc-/GPX4 signaling pathway scavenge free radicals prevent lipid peroxidation. this research indicate regulates during osteoarthritis, open new field

Language: Английский

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Fighting age-related orthopedic diseases: focusing on ferroptosis

Bone Research, Journal Year: 2023, Volume and Issue: 11(1)

Published: March 1, 2023

Abstract Ferroptosis, a unique type of cell death, is characterized by iron-dependent accumulation and lipid peroxidation. It closely related to multiple biological processes, including iron metabolism, polyunsaturated fatty acid the biosynthesis compounds with antioxidant activities, glutathione. In past 10 years, increasing evidence has indicated potentially strong relationship between ferroptosis onset progression age-related orthopedic diseases, such as osteoporosis osteoarthritis. Therefore, in-depth knowledge regulatory mechanisms in diseases may help improve disease treatment prevention. This review provides an overview recent research on its influences bone cartilage homeostasis. begins brief systemic metabolism ferroptosis, particularly potential ferroptosis. presents discussion role promotion loss degradation inhibition osteogenesis. Finally, it focuses future targeting treat intention inspiring further clinical development therapeutic strategies.

Language: Английский

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Single cell RNA-seq analysis identifies ferroptotic chondrocyte cluster and reveals TRPV1 as an anti-ferroptotic target in osteoarthritis

EBioMedicine, Journal Year: 2022, Volume and Issue: 84, P. 104258 - 104258

Published: Sept. 19, 2022

Language: Английский

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Astaxanthin attenuates osteoarthritis progression via inhibiting ferroptosis and regulating mitochondrial function in chondrocytes

Chemico-Biological Interactions, Journal Year: 2022, Volume and Issue: 366, P. 110148 - 110148

Published: Sept. 6, 2022

Language: Английский

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Lipid peroxidation in osteoarthritis: focusing on 4-hydroxynonenal, malondialdehyde, and ferroptosis

Cell Death Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: Aug. 29, 2023

Abstract Osteoarthritis (OA) is a multifactorial and increasingly prevalent degenerative disease that affects the whole joint. The pathogenesis of OA poorly understood there lack therapeutic interventions to reverse pathological process this disease. Accumulating studies have shown overproduction reactive oxygen species (ROS) ROS-induced lipid peroxidation are involved in OA. 4-Hydroxy-2-nonenal (4-HNE) malondialdehyde (MDA) received considerable attention for their role cartilage degeneration subchondral bone remodeling during development. Ferroptosis form cell death characterized by control membrane recent suggested chondrocyte ferroptosis contributes progression. In review, we aim discuss peroxidation-derived 4-HNE MDA progression addition, potential controlling accumulation inhibiting discussed.

Language: Английский

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The gut microbiota metabolite capsiate regulate SLC2A1 expression by targeting HIF‐1α to inhibit knee osteoarthritis‐induced ferroptosis

Aging Cell, Journal Year: 2023, Volume and Issue: 22(6)

Published: March 8, 2023

Abstract Ferroptosis is an iron‐dependent cell death that has been found to aggravate the progression of osteoarthritis (OA) and gut microbiota‐ OA axis refers bidirectional information network between microbiota OA, which may provide a new way protect OA. However, role microbiota‐derived metabolites in ferroptosis‐relative remains unclear. The objective this study was analyze protective effect its metabolite capsiate (CAT) on vivo vitro experiments. From June 2021 February 2022, 78 patients were evaluated retrospectively divided into two groups: health group ( n = 39) 40). Iron oxidative stress indicators determined peripheral blood samples. And then experiments, surgically destabilized medial meniscus (DMM) mice model established treated with CAT or Ferric Inhibitor‐1 (Fer‐1). Solute Carrier Family 2 Member 1 (SLC2A1) short hairpin RNA (shRNA) utilized inhibit SLC2A1 expression. Serum iron increased significantly but total binding capacity decreased than healthy people p < 0.0001). least absolute shrinkage selection operator clinical prediction suggested serum iron, capacity, transferrin, superoxide dismutase all independent predictors 0.001). Bioinformatics results SLC2A1, Metastasis‐Associated Lung Adenocarcinoma Transcript (MALAT1), HIF‐1α (Hypoxia Inducible Factor Alpha)‐related signaling pathways play important homeostasis In addition, 16s sequencing untargeted metabolomics used find negatively correlated Osteoarthritis Research Society International (OARSI) scores for chondrogenic degeneration 0.0017). Moreover, reduced ferroptosis‐dependent vitro. against could be eliminated by silencing SLC2A1. upregulated levels DMM group. HIF‐1α, MALAT1, apoptosis after knockout chondrocyte cells Finally, downregulation expression Adeno‐associated Virus (AAV) ‐SLC2A1 shRNA improves vivo. Our findings indicated inhibited HIF‐1a activating

Language: Английский

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Iron homeostasis and ferroptosis in human diseases: mechanisms and therapeutic prospects

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Oct. 14, 2024

Iron, an essential mineral in the body, is involved numerous physiological processes, making maintenance of iron homeostasis crucial for overall health. Both overload and deficiency can cause various disorders human diseases. Ferroptosis, a form cell death dependent on iron, characterized by extensive peroxidation lipids. Unlike other kinds classical unprogrammed death, ferroptosis primarily linked to disruptions metabolism, lipid peroxidation, antioxidant system imbalance. Ferroptosis regulated through transcription, translation, post-translational modifications, which affect cellular sensitivity ferroptosis. Over past decade or so, diseases have been as part their etiology, including cancers, metabolic disorders, autoimmune diseases, central nervous cardiovascular musculoskeletal Ferroptosis-related proteins become attractive targets many major that are currently incurable, some regulators shown therapeutic effects clinical trials although further validation potential needed. Therefore, in-depth analysis its molecular mechanisms may offer additional strategies prevention treatment. In this review, we discuss significance contribution etiology development along with evidence supporting targeting approach. Importantly, evaluate recent promising interventions, providing guidance future targeted treatment therapies against

Language: Английский

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Baicalein limits osteoarthritis development by inhibiting chondrocyte ferroptosis

Free Radical Biology and Medicine, Journal Year: 2023, Volume and Issue: 196, P. 108 - 120

Published: Jan. 16, 2023

Language: Английский

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