Inhibition of Nrf2/HO-1 signaling leads to increased activation of the NLRP3 inflammasome in osteoarthritis

Arthritis Research & Therapy, Journal Year: 2019, Volume and Issue: 21(1)

Published: Dec. 1, 2019

Abstract Introduction Osteoarthritis (OA) is an inflammatory disease of the joints that causes progressive disability in elderly. Reactive oxygen species (ROS) play important role OA development; they may activate NLRP3 inflammasome, thereby inducing secretion proinflammatory IL-1β and IL-18, leading to aggravation downstream response. Nrf2 a key transcription factor regulates expression antioxidant enzymes protect against oxidative stress tissue damage. We aimed explore underlying mechanism development by investigating NLRP3, ASC, Nrf2, HO-1 synovia their regulatory networks OA. Methods Human total knee replacement samples were subjected histology micro-CT analysis determine pathological changes cartilage subchondral bone assess inflammation-related markers synovial immunohistochemistry (IHC), qRT-PCR, Western blot. To investigate these animal model, adult Sprague-Dawley rats anterior cruciate ligament transection medial meniscectomy. Articular also determined same methods used for human samples. Finally, SW982 cells stimulated with lipopolysaccharide (LPS) as vitro cell model. The correlation between was confirmed knocking down or Nrf2. Results Cartilage destruction sclerosis found patients model rats. Significantly increased levels from patients. synovium upregulated group compared sham group. Furthermore, HO-1, IL-1β, IL-18 LPS-treated dose-dependent manner. As expected, upregulated, downregulated after silencing. However, did not affect Conclusions ROS-induced be main cause inflammasome activation subsequent release factors during development. Nrf2/HO-1 signaling could pathway which contribute progression Herein, we discovered novel production facilitate prevention treatment

Language: Английский

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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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Pyroptosis is a critical immune-inflammatory response involved in atherosclerosis

Pharmacological Research, Journal Year: 2021, Volume and Issue: 165, P. 105447 - 105447

Published: Jan. 29, 2021

Language: Английский

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Anti-inflammatory and immunoregulatory effects of icariin and icaritin

Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 151, P. 113180 - 113180

Published: May 27, 2022

Inflammation and immunity dysregulation have received widespread attention in recent years due to their occurrence the pathophysiology of many conditions. In this regard, several pharmacological studies been conducted aiming evaluate potential anti-inflammatory immunomodulatory effects phytochemicals. Epimedium, a traditional Chinese medicine, is often used as tonic, aphrodisiac, anti-rheumatic agent. Icariin (ICA) main active ingredient Epimedium is, once ingested, mainly metabolized into Icaritin (ICT). Data from vitro vivo suggested that ICA its metabolite (ICT) regulated functions activation immune cells, modulated release inflammatory factors, restored aberrant signaling pathways. ICT were also involved responses diseases, including multiple sclerosis, asthma, atherosclerosis, lupus nephritis, bowel rheumatoid arthritis, cancer. Yet, data showed exhibited similar but not identical pharmacokinetic properties. Therefore, based on higher solubility bioavailability, well trends indicating single-ingredient compounds offer broader safer therapeutic capabilities, delivery systems treatment represent interesting avenues with promising clinical applications. study, we reviewed mechanisms, properties ICT.

Language: Английский

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Pyroptosis and degenerative diseases of the elderly

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(2)

Published: Feb. 9, 2023

Abstract Pyroptosis is a recently described mechanism of programmed cell death mediated by proteins the gasdermin family. Widely recognized signaling cascades include classical, non-classical, caspase-3-dependent E and caspase-8-dependent D pathways. Additional pyroptotic pathways have been subsequently reported. With rising prevalence advanced age, role pyroptosis in degenerative diseases elderly has attracted increased research attention. This article reviews primary mechanisms summarizes progress such as presbycusis, age-related macular degeneration, Alzheimer’s disease, intervertebral disc osteoarthritis.

Language: Английский

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Icariin inhibits chondrocyte ferroptosis and alleviates osteoarthritis by enhancing the SLC7A11/GPX4 signaling

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 133, P. 112010 - 112010

Published: April 17, 2024

Chondrocyte ferroptosis plays a critical role in the pathogenesis of osteoarthritis (OA), regulated by SLC7A11/GPX4 signaling pathway. Icariin (ICA), flavonoid glycoside, exhibits strong anti-inflammatory and antioxidant activities. This study investigated whether ICA could modulate to inhibit chondrocyte alleviate OA.

Language: Английский

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Activating Nrf2 signalling alleviates osteoarthritis development by inhibiting inflammasome activation

Journal of Cellular and Molecular Medicine, Journal Year: 2020, Volume and Issue: 24(22), P. 13046 - 13057

Published: Sept. 23, 2020

Abstract Osteoarthritis (OA), which is characterized by proliferation of subchondral bone and the degeneration articular cartilage, most prevalent human arthritis. Nod‐like receptor pyrin domain 3 (NLRP3) inflammasome a hot spot in recent year has been reported to be associated with OA synovial inflammation. However, there are few studies on NLRP3 chondrocyte. Licochalcone A (Lico A), compound extracted from Glycyrrhiza species, various biological effects such as anti‐inflammation, anti‐apoptotic, anti‐cancer anti‐oxidation. In this study, we investigated protective effect Lico chondrocytes stimulated lipopolysaccharide (LPS) surgically induced models. vitro, could reduce expression NLRP3, apoptosis‐associated speck‐like protein (ASC), Gasdermin D (GSDMD), caspase‐1, interleukin‐1beta (IL‐1β) IL‐18, indicated that attenuates LPS‐induced pyroptosis. addition, ameliorates degradation extracellular matrix (ECM) enhancing aggrecan collagen‐II. Meanwhile, found inhibits via nuclear factor erythroid‐2‐related 2 (Nrf2)/haeme oxygenase‐1(HO‐1)/nuclear kappa‐B (NF‐κB) axis. And Nrf2 small interfering RNA (siRNA) reverse anti‐pyroptosis mouse chondrocytes. vivo, mitigates progression model reduces Research Society International (OARSI) scores. Thus, may have therapeutic potential OA.

Language: Английский

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Icariin enhances cell survival in lipopolysaccharide‑induced synoviocytes by suppressing ferroptosis via the Xc‑/GPX4 axis

Experimental and Therapeutic Medicine, Journal Year: 2020, Volume and Issue: 21(1)

Published: Nov. 25, 2020

The mechanism of action synovitis, as the vital pathological process rheumatoid arthritis and osteoarthritis, remains to be elucidated. effects icariin (ICA), which is a promising therapeutic agent in was investigated present study. In addition, ferroptosis, cell involved several diseases, also studied synovitis for first time. Lipopolysaccharide (LPS)‑induced synoviocytes served model. cells were divided into control, LPS experimental groups treated with different concentrations ICA. Cell viability determined by Counting Kit‑8 assay death flow cytometry. expression levels proteins (GPX4, SLC7A11, SLC3A2L, TRF, Nrf2 NCOA4) measured western blotting. Quantification malondialdehyde (MDA), iron glutathione peroxidase 4 (GPX4) activity performed via using corresponding kits. increased, decreased LPS‑induced synoviocytes. Furthermore, MDA content elevated GPX reduced Transferrin receptor protein 1 nuclear coactivator upregulated Xc‑/GPX4 axis, well factor erythroid 2‑related 2, treatment. All aforementioned affects alleviated ICA concentration‑dependent manner. counteracted RSL3, ferroptosis activator, on viability, lipid peroxidation, relative protects from induced LPS, inhibition activating can exploited new strategy synovitis.

Language: Английский

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Guidelines for Regulated Cell Death Assays: A Systematic Summary, A Categorical Comparison, A Prospective

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: March 4, 2021

Over the past few years, field of regulated cell death continues to expand and novel mechanisms that orchestrate multiple pathways are being unveiled. Meanwhile, researchers focused on targeting these which closely associated with various diseases for diagnosis, treatment, prognosis. However, complexity difficulties distinguishing among types make it harder carry out work delay its progression. Here, we provide a systematic guideline fundamental detection distinction major following morphological, biochemical, functional perspectives. Moreover, comprehensive evaluation different assay methods is critically reviewed, helping reliable selection from assays. Also, highlight recent events have demonstrated some processes, including newly reported biomarkers (e.g., non-coding RNA, exosomes, proteins) techniques.

Language: Английский

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Icariin alleviates osteoarthritis by regulating autophagy of chondrocytes by mediating PI3K/AKT/mTOR signaling

Bioengineered, Journal Year: 2021, Volume and Issue: 12(1), P. 2984 - 2999

Published: Jan. 1, 2021

Osteoarthritis (OA) is a chronic degenerative disease that significantly impacts the quality of life elderly population. Recently, pathogenesis OA has been reported to involve autophagy in chondrocytes. Intriguingly, icariin, one main components epimedium, exerts multiple pharmacological effects, including protective effect against chondrocyte damage. Thus, we aimed investigate therapeutic icariin on and its potential underlying mechanism by using rat model OA. After treatment with or an activator (rapamycin) inhibitor (3-methyladenine), viability was measured CCK-8 assay, apoptosis chondrocytes evaluated acridine orange-propidium iodide assay flow cytometry, tissue pathological state assessed micro-CT scanning safranin O staining. Furthermore, immunohistochemical staining used measure expression level Beclin-1 immunofluorescence labeling visualize LC3 expression, western blotting determine levels proteins key PI3K signaling pathway. The apoptotic rate markedly elevated 3-methyladenine suppressed rapamycin icariin; genes were drastically downregulated group upregulated groups; PI3K/AKT/mTOR pathway activated inhibited icariin. Notably, following severe cartilage tissues substantially alleviated, this accompanied tissues. Taken together, these findings indicate alleviates regulating mediating signaling.

Language: Английский

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