Mechanism of NLRP3 inflammasome intervention for synovitis in knee osteoarthritis: A review of TCM intervention

Han, Xianfu; Lin, Demin; Huang, Weiwei; Li, Dingpeng; Li, Ning; Xie, Xingwen

doi:10.3389/fgene.2023.1159167

Cited by 4 publications

(2 citation statements)

References 64 publications

(57 reference statements)

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“…Previous studies have demonstrated that canonical inflammasomes and the NLRP3 inflammasome are actively involved in the pathogenesis of OA and that selective targeting of canonical inflammasomes is an emerging pharmacological strategy for OA therapy [70][71][72][73][74]. Accumulating evidence has revealed that non-canonical inflammasomes are possible players in OA pathogenesis.…”

Section: Osteoarthritis (Oa)mentioning

confidence: 99%

Roles of the Caspase-11 Non-Canonical Inflammasome in Rheumatic Diseases

2024

IJMS

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Inflammasomes are intracellular multiprotein complexes that activate inflammatory signaling pathways. Inflammasomes comprise two major classes: canonical inflammasomes, which were discovered first and are activated in response to a variety of pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs), and non-canonical inflammasomes, which were discovered recently and are only activated in response to intracellular lipopolysaccharide (LPS). Although a larger number of studies have successfully demonstrated that canonical inflammasomes, particularly the NLRP3 inflammasome, play roles in various rheumatic diseases, including rheumatoid arthritis (RA), infectious arthritis (IR), gouty arthritis (GA), osteoarthritis (OA), systemic lupus erythematosus (SLE), psoriatic arthritis (PA), ankylosing spondylitis (AS), and Sjögren’s syndrome (SjS), the regulatory roles of non-canonical inflammasomes, such as mouse caspase-11 and human caspase-4 non-canonical inflammasomes, in these diseases are still largely unknown. Interestingly, an increasing number of studies have reported possible roles for non-canonical inflammasomes in the pathogenesis of various mouse models of rheumatic disease. This review comprehensively summarizes and discusses recent emerging studies demonstrating the regulatory roles of non-canonical inflammasomes, particularly focusing on the caspase-11 non-canonical inflammasome, in the pathogenesis and progression of various types of rheumatic diseases and provides new insights into strategies for developing potential therapeutics to prevent and treat rheumatic diseases as well as associated diseases by targeting non-canonical inflammasomes.

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Section: Osteoarthritis (Oa)mentioning

confidence: 99%

Roles of the Caspase-11 Non-Canonical Inflammasome in Rheumatic Diseases

2024

IJMS

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“…In recent years, the research in the field of KOA has been increasingly in-depth. Current studies focus on cytokines, particularly those crucial to inflammation (12,13), as well as the mechanisms of gene expression (14,15) and signal transduction pathways (16)(17)(18). The TNF family and MMP enzyme series have been frequently reported to be associated with KOA (13, [19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

Evidence supported by Mendelian randomization: impact on inflammatory factors in knee osteoarthritis

Xu,

Ma,

et al. 2024

Front. Med.

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BackgroundPrior investigations have indicated associations between Knee Osteoarthritis (KOA) and certain inflammatory cytokines, such as the interleukin series and tumor necrosis factor-alpha (TNFα). To further elaborate on these findings, our investigation utilizes Mendelian randomization to explore the causal relationships between KOA and 91 inflammatory cytokines.MethodsThis two-sample Mendelian randomization utilized genetic variations associated with KOA from a large, publicly accessible Genome-Wide Association Study (GWAS), comprising 2,227 cases and 454,121 controls of European descent. The genetic data for inflammatory cytokines were obtained from a GWAS summary involving 14,824 individuals of European ancestry. Causal relationships between exposures and outcomes were primarily investigated using the inverse variance weighted method. To enhance the robustness of the research results, other methods were combined to assist, such as weighted median, weighted model and so on. Multiple sensitivity analysis, including MR-Egger, MR-PRESSO and leave one out, was also carried out. These different analytical methods are used to enhance the validity and reliability of the final results.ResultsThe results of Mendelian randomization indicated that Adenosine Deaminase (ADA), Fibroblast Growth Factor 5(FGF5), and Hepatocyte growth factor (HFG) proteins are protective factors for KOA (IVWADA: OR = 0.862, 95% CI: 0.771–0.963, p = 0.008; IVWFGF5: OR = 0.850, 95% CI: 0.764–0.946, p = 0.003; IVWHFG: OR = 0.798, 95% CI: 0.642–0.991, p = 0.042), while Tumor necrosis factor (TNFα), Colony-stimulating factor 1(CSF1), and Tumor necrosis factor ligand superfamily member 12(TWEAK) proteins are risk factors for KOA. (IVWTNFα: OR = 1.319, 95% CI: 1.067–1.631, p = 0.011; IVWCSF1: OR = 1.389, 95% CI: 1.125–1.714, p = 0.002; IVWTWEAK: OR = 1.206, 95% CI: 1.016–1.431, p = 0.032).ConclusionThe six proteins identified in this study demonstrate a close association with the onset of KOA, offering valuable insights for future therapeutic interventions. These findings contribute to the growing understanding of KOA at the microscopic protein level, paving the way for potential targeted therapeutic approaches.

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Network pharmacological analysis on the mechanism of Coix seed decoction for osteoarthritis of the knee

et al. 2023

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Based on network pharmacology methods, we explored the mechanism of the classic Chinese medicine formula Coix seed decoction (CSD) in treating knee osteoarthritis (KOA). We searched each single drug in the CSD in the traditional Chinese medicine systematic pharmacology database in turn to obtain information on the active ingredients and target proteins of the CSD, and obtain the name of the genes corresponding to the target proteins through the UniProt database. We collected KOA-related genes from DisGeNET, GeneCards, comparative toxicogenomics database, and MalaCards database. The Venny online tool identified potential therapeutic targets by intersecting CSD and KOA target genes, while gene ontology and Kyoto encyclopedia of genes and genomes analysis was performed using the Oebiotech Cloud Platform. A protein-protein interaction network was established using the String database; a “CSD-active ingredient-target gene-KOA” network plot was constructed using Cytoscape 3.9.1 software and screened for key targets and hub targets. Finally, molecular docking was performed for hub genes with high Degree values. A total of 227 effective target genes for CSD and 8816 KOA-related target genes were obtained, as well as 191 cross-target genes for CSD and KOA. We screened 37 key gene targets and identified the top 10 hub target genes in descending order of Degree value using protein-protein interaction and Cytoscape 3.9.1 software (TNF, IL-6, MMP-9, IL-1β, AKT-1, VEGFα, STAT-3, PTGS-2, IL-4, TP53). Gene ontology analysis showed that the biological process of CSD treatment of KOA mainly involves cytokine-mediated signaling pathway, negative regulation of apoptotic process, cellular response to hypoxia, cellular response to cadmium ion, response to estradiol, and extrinsic apoptotic signaling pathway in absence of ligand. Kyoto encyclopedia of genes and genomes analysis revealed major signaling pathways including Cellular senescence, TNF signaling pathway, and PI3K-Akt signaling pathway. The molecular docking results show that the core components bind well to the core targets. In conclusion, CSD may exert therapeutic effects on KOA by inhibiting pathological processes such as inflammatory response, apoptosis, cellular senescence, and oxidative stress.

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Mechanism of NLRP3 inflammasome intervention for synovitis in knee osteoarthritis: A review of TCM intervention

Cited by 4 publications

References 64 publications

Roles of the Caspase-11 Non-Canonical Inflammasome in Rheumatic Diseases

Roles of the Caspase-11 Non-Canonical Inflammasome in Rheumatic Diseases

Evidence supported by Mendelian randomization: impact on inflammatory factors in knee osteoarthritis

Network pharmacological analysis on the mechanism of Coix seed decoction for osteoarthritis of the knee

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