Targeting inflammasome-dependent mechanisms as an emerging pharmacological approach for osteoarthritis therapy

Ramírez-Pérez, Sergio; Reyes-Pérez, Itzel Viridiana; Martínez‐Fernández, Diana Emilia; Hernández-Palma, Luis Alexis; Bhattaram, Pallavi

doi:10.1016/j.isci.2022.105548

Cited by 15 publications

(9 citation statements)

References 122 publications

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“…The results show that resveratrol could delay articular cartilage degeneration by balancing HIF-1α and HIF-2α expressions and promoting chondrocyte autophagy, thereby regulating AMPK/mTOR signaling pathway . Similarly to our study, resveratrol was also reported to induce an inadequate assembly of ASC on the mitochondria and inhibit NF-κB responses, leading to the inactivation of NLRP3 inflammasome. − However, the low bioavailability and rapid metabolization made the clinical application of these natural compounds ineffective. ,, PT, a dimethyl ether analog of resveratrol, shows better health effects due to its two dimethyl groups, which increase its bioavailability and result in a longer half-life in vivo . , In particular, several studies suggested that increasing the water solubility of PT significantly improves its oral absorption, thereby promoting the research on the production of highly water-soluble PT-modified compounds and increasing the research potential of PT. − Our previous study demonstrated that PT could significantly attenuate renal fibrosis by downregulating NLRP3 inflammasome activation . Similar to the results in this study, PT affected the regulation of the NLRP3 inflammasome by reducing the expression of TGF-β-induced NLRP3.…”

Section: Discussionsupporting

confidence: 75%

Pterostilbene Protects against Osteoarthritis through NLRP3 Inflammasome Inactivation and Improves Gut Microbiota as Evidenced by In Vivo and In Vitro Studies

Lee,

Chang,

Cheng

et al. 2024

J. Agric. Food Chem.

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Osteoarthritis (OA) is a persistent inflammatory disease, and long-term clinical treatment often leads to side effects. In this study, we evaluated pterostilbene (PT), a natural anti-inflammatory substance, for its protective effects and safety during prolonged use on OA. Results showed that PT alleviated the loss of chondrocytes and widened the narrow joint space in an octacalcium phosphate (OCP)-induced OA mouse model (n = 3). In vitro experiments demonstrate that PT reduced NLRP3 inflammation activation (relative protein expression: C: 1 ± 0.09, lipopolysaccharide (LPS): 1.14 ± 0.07, PT: 0.91 ± 0.07, LPS + PT: 0.68 ± 0.04) and the release of inflammatory cytokines through NF-κB signaling inactivation (relative protein expression: C: 1 ± 0.03, LPS: 3.49 ± 0.02, PT: 0.66 ± 0.08, LPS + PT: 2.78 ± 0.05), ultimately preventing cartilage catabolism. Interestingly, PT also altered gut microbiota by reducing inflammation-associated flora and increasing the abundance of healthy bacteria in OA groups. Collectively, these results suggest that the PT can be considered as a protective strategy for OA.

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Section: Discussionsupporting

confidence: 75%

Pterostilbene Protects against Osteoarthritis through NLRP3 Inflammasome Inactivation and Improves Gut Microbiota as Evidenced by In Vivo and In Vitro Studies

Lee,

Chang,

Cheng

et al. 2024

J. Agric. Food Chem.

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“…Inflammation and metabolic disorders play a very important role in the progression of osteoarthritis ( 10 , 11 ). Risk factors, including diabetes, hypertension, and hyperlipidemia, are largely involved in osteoarthritis through the release of inflammatory and adipokines that accelerate the progression of osteoarthritis by driving articular cartilage degeneration and bone marrow lesions ( 12 ). Several theories describe how MetS risk factors affect the progression of OA, such as high blood pressure can cause subchondral ischemia, abnormal lipids can cause lipid deposition in chondrocytes, and high blood glucose can cause oxidative stress and low inflammation, eventually leading to cartilage destruction ( 13 ).…”

Section: Introductionmentioning

confidence: 99%

Identification of immune-associated genes in diagnosing osteoarthritis with metabolic syndrome by integrated bioinformatics analysis and machine learning

Wang

et al. 2023

Front. Immunol.

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BackgroundIn the pathogenesis of osteoarthritis (OA) and metabolic syndrome (MetS), the immune system plays a particularly important role. The purpose of this study was to find key diagnostic candidate genes in OA patients who also had metabolic syndrome.MethodsWe searched the Gene Expression Omnibus (GEO) database for three OA and one MetS dataset. Limma, weighted gene co-expression network analysis (WGCNA), and machine learning algorithms were used to identify and analyze the immune genes associated with OA and MetS. They were evaluated using nomograms and receiver operating characteristic (ROC) curves, and finally, immune cells dysregulated in OA were investigated using immune infiltration analysis.ResultsAfter Limma analysis, the integrated OA dataset yielded 2263 DEGs, and the MetS dataset yielded the most relevant module containing 691 genes after WGCNA, with a total of 82 intersections between the two. The immune-related genes were mostly enriched in the enrichment analysis, and the immune infiltration analysis revealed an imbalance in multiple immune cells. Further machine learning screening yielded eight core genes that were evaluated by nomogram and diagnostic value and found to have a high diagnostic value (area under the curve from 0.82 to 0.96).ConclusionEight immune-related core genes were identified (FZD7, IRAK3, KDELR3, PHC2, RHOB, RNF170, SOX13, and ZKSCAN4), and a nomogram for the diagnosis of OA and MetS was established. This research could lead to the identification of potential peripheral blood diagnostic candidate genes for MetS patients who also suffer from OA.

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“…NLRP3 and NLRP1 are important inflammasome components in OA, triggering pathogenic processes in macrophages. Targeting inflammasomes in chondrocytes and fibroblast-like synoviocytes presents a promising strategy for developing OA disease-modifying therapies [38].…”

Section: Discussionmentioning

confidence: 99%

Quantum Molecular Resonance Inhibits NLRP3 Inflammasome/Nitrosative Stress and Promotes M1 to M2 Macrophage Polarization: Potential Therapeutic Effect in Osteoarthritis Model In Vitro

et al. 2023

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This study aimed to investigate the anti-inflammatory effects of Quantum Molecular Resonance (QMR) technology in an in vitro model of osteoarthritis-related inflammation. The study used THP-1-derived macrophages stimulated with lipopolysaccharide and hyaluronic acid fragments to induce the expression of inflammatory cytokines and nitrosative stress. QMR treatment inhibited COX-2 and iNOS protein expression and activity and reduced NF-κB activity. Furthermore, QMR treatment led to a significant reduction in peroxynitrite levels, reactive nitrogen species that can form during inflammatory conditions, and restored tyrosine nitration values to those similar to sham-exposed control cells. We also investigated the effect of QMR treatment on inflammasome activation and macrophage polarization in THP-1-derived macrophages. Results showed that QMR treatment significantly decreased NLRP3 and activated caspase-1 protein expression levels and downregulated IL-18 and IL-1β protein expression and secretion. Finally, our findings indicate that QMR treatment induces a switch in macrophage polarization from the M1 phenotype to the M2 phenotype.

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Targeting inflammasome-dependent mechanisms as an emerging pharmacological approach for osteoarthritis therapy

Cited by 15 publications

References 122 publications

Pterostilbene Protects against Osteoarthritis through NLRP3 Inflammasome Inactivation and Improves Gut Microbiota as Evidenced by In Vivo and In Vitro Studies

Pterostilbene Protects against Osteoarthritis through NLRP3 Inflammasome Inactivation and Improves Gut Microbiota as Evidenced by In Vivo and In Vitro Studies

Identification of immune-associated genes in diagnosing osteoarthritis with metabolic syndrome by integrated bioinformatics analysis and machine learning

Quantum Molecular Resonance Inhibits NLRP3 Inflammasome/Nitrosative Stress and Promotes M1 to M2 Macrophage Polarization: Potential Therapeutic Effect in Osteoarthritis Model In Vitro

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