Therapeutic potential of targeting the IRF2/POSTN/Notch1 axis in nucleus pulposus cells for intervertebral disc degeneration

Journal of Neuroinflammation, Год журнала: 2025, Номер 22(1)

Опубликована: Янв. 22, 2025

Intervertebral disc degeneration (IDD) is a leading cause of low back pain, often linked to inflammation and pyroptosis in nucleus pulposus (NP) cells. The role Periostin (POSTN) IDD remains unclear. This study aims investigate the influence POSTN on NLRP3 inflammasome activation NP cells during IDD. IVD samples were collected from patients undergoing spinal surgery classified according Pfirrmann grading system. Human cultured treated with IL-1β induce pyroptotic phenotype. Western blotting, Immunofluorescence (IF), immunohistochemistry (IHC) assessed expression levels relevant proteins. Chromatin immunoprecipitation (ChIP) luciferase reporter assays verified binding IRF2 GSDMD promoters evaluated target genes. severity was using MRI histological analysis. Deletion significantly alleviated by suppressing activity found aggravate cell activating through NF-κB (P65) cGAS/STING signaling pathways. Furthermore, interacted Notch1 expression. identified as regulator at transcriptional level, contributing pyroptosis. also directly induced GSDMD, mediating Chemical screening Glucosyringic acid (GA) direct inhibitor POSTN, which delayed progression. elucidates pivotal highlights GA promising therapeutic candidate for These findings provide new insights into molecular mechanisms potential avenues treatment.

Язык: Английский

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End Plate Chondrocyte-Derived Exosomal miR-133a-3p Alleviates Intervertebral Disc Degeneration by Targeting the NF-κB Signaling Pathway through the miR-133a-3p/MAML1 Axis

Molecular Pharmaceutics, Год журнала: 2025, Номер unknown

Опубликована: Фев. 3, 2025

Chondrocyte-derived exosomes have shown efficacy in differentiating osteoarthritis-affected cartilage. Intervertebral disc degeneration (IVDD) and osteoarthritis often affect facet joints of the spine show common epidemiological pathophysiological characteristics. However, potential chondrocyte-derived for treating IVDD remains unclear. The present study aimed to confirm effect end plate (EPC-Exo) on elucidate underlying mechanism. EPC-Exos were isolated identified by ultracentrifugation, Western blotting, electron microscopy, nanoparticle tracking analysis. In vitro, EPC-Exo uptake nucleus pulposus (NP) cells reduced cell death blocking nuclear factor-κB (NF-κB) signaling pathway. vivo study, injected into rat intervertebral discs mitigated lipopolysaccharide-induced IVDD, as revealed a decreased loss height improved magnetic resonance imaging findings histological scores. Bioinformatics sequencing analyses indicated that alleviated through miR-133a-3p/MAML1 axis. suggests incidence via axis-mediated suppression NF-κB signaling, which prevented pyroptosis NP cells.

Язык: Английский

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Causal Relationship Between Mitochondrial DNA Copy Number and Intervertebral Disc Degeneration: A Bidirectional 2-Sample Mendelian Randomization Study

World Neurosurgery, Год журнала: 2025, Номер 196, С. 123732 - 123732

Опубликована: Март 13, 2025

Язык: Английский

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The intricate ballet of inflammation and autophagy: Insights from Mycoplasma gallisepticum-infected HD11 cells

Cytokine, Год журнала: 2025, Номер 188, С. 156895 - 156895

Опубликована: Фев. 18, 2025

Язык: Английский

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Piezo1 promotes intervertebral disc degeneration through the Ca2+/F-actin/Yap signaling axis

Molecular Medicine, Год журнала: 2025, Номер 31(1)

Опубликована: Март 8, 2025

Abstract Background Piezo1 is a mechanically sensitive cation channel expressed in various tissues of the human body and has multiple roles both physiological pathological processes. However, its role occurrence development intervertebral disc degeneration (IVDD) not fully understood. Methods In present study, an IVDD mouse model small interfering (si)RNA was used to investigate progression. Furthermore, Ca 2+ inhibitor, BAPTA-AM, F-actin cytoskeleton polymerization Latrunculin A, were employed examine influx dynamics Piezo1-mediated Additionally, Yes-associated protein (Yap) involvement Yap Piezo1-induced Results The findings study indicated that positively associated with upregulation promoted via facilitating cartilage endplate (CEP) calcification. inhibited extracellular matrix degradation CEP chondrocyte degeneration. Moreover, it found activated through F-actin-mediated non-canonical pathway siRNA upregulation-induced Conclusion Overall, results indicate increased expression closely related /F-actin/Yap axis contributes this process. Thus, targeting may provide new strategy for treatment IVDD.

Язык: Английский

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Mitochondrial DNA in Exercise-Mediated Innate Immune Responses

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(7), С. 3069 - 3069

Опубликована: Март 27, 2025

Mitochondria are considered as "the plant of power" with cells for a long time. However, recent researches suggest that mitochondria also take part in innate immune response to great extent. Remarkably, mtDNA was reported have immunnostimulatory potential 2004. Since then, there has been rapid growth understanding the role immune. The is released into cytosol, extracellular environment, or circulating blood through BAK/BAX pore, mPTP, and GSDMD pore upon mitochondrial damage, where it recognized by PRRs including TLR9, cGAS, NLRP3, thereby triggering response. On other hand, regular exercise an effective intervention strategy Some studies show chronic moderate-intensity endurance exercise, resistance training, HIIT, acute enhance function promoting transcription replication, thus blunting abnormal release excessive contrary, high-intensity elicits opposite effect. Nevertheless, only very small body research far performed illustrate impact on mtDNA-driven response, overall review lacking. In light these, we summarize current knowledge mechanism mediating mtDNA, influence leakage, hoping pave way investigate new diagnostic therapeutic approaches immunopathies.

Язык: Английский

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Mitochondria-dependent innate immunity: A potential therapeutic target in Flavivirus infection

International Immunopharmacology, Год журнала: 2025, Номер 154, С. 114551 - 114551

Опубликована: Март 31, 2025

Язык: Английский

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Crosstalk between Dysfunctional Mitochondria and Proinflammatory Responses during Viral Infections

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(17), С. 9206 - 9206

Опубликована: Авг. 24, 2024

Mitochondria play pivotal roles in sustaining various biological functions including energy metabolism, cellular signaling transduction, and innate immune responses. Viruses exploit metabolic synthesis to facilitate viral replication, potentially disrupting mitochondrial subsequently eliciting a cascade of proinflammatory responses host cells. Additionally, the disruption membranes is involved regulation. During infections, mitochondria orchestrate through generation reactive oxygen species (ROS) release DNA, which serves as an effective defense mechanism against virus invasion. The targeting damage may represent novel approach antiviral intervention. This review summarizes regulatory underlying response induced by during providing new insights for strategies.

Язык: Английский

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Electroacupuncture preconditioning protects against myocardial ischemia-reperfusion injury by modulating dynamic inflammatory response

Heliyon, Год журнала: 2023, Номер 9(9), С. e19396 - e19396

Опубликована: Авг. 29, 2023

BackgroundThe protective effects of electroacupuncture (EA) preconditioning against myocardial ischemia reperfusion injury (MIRI) have been reported. However, the underlying mechanism remains unclear. Recent research has indicated that dynamic inflammatory response following MIRI plays an essential role in progression injury. This study aimed to investigate EA on rats and explore relevant from perspective response.MethodsA model was employed, were subjected Neiguan for four days prior modeling. The effect evaluated by echocardiography, Evans blue triphenyltetrazolium chloride staining. Real-time polymerase chain reaction, Western blot, hematoxylin & eosin staining, immunohistochemistry utilized detect content mitochondrial DNA, NOD receptor family protein 3 (NLRP3) inflammasome activation, neutrophil recruitment macrophage infiltration blood samples myocardium below ligation.ResultsWe found could accelerate recovery left ventricle function after reduce infarction area, thereby protecting MIRI. Furthermore, observed ameliorate impairment, level plasma modulate NLRP3 attenuate infiltration, promote polarization M1 macrophages towards M2 MIRI.ConclusionEA mtDNA, suppress overactivation inflammasome, facilitate transition acute pro-inflammatory phase anti-inflammatory reparative MIRI, ultimately confer cardioprotective benefits.

Язык: Английский

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Calenduloside E ameliorates non-alcoholic fatty liver disease via modulating a pyroptosis-dependent pathway.

Journal of Ethnopharmacology, Год журнала: 2023, Номер 319, С. 117239 - 117239

Опубликована: Сен. 28, 2023

Язык: Английский

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