Lysyl Oxidase-Like 1 (LOXL1) Up-Regulation in Chondrocytes Promotes M1 Macrophage Activation in Osteoarthritis via NF-κB and STAT3 Signaling

ImmunoTargets and Therapy, Год журнала: 2025, Номер Volume 14, С. 259 - 278

Опубликована: Март 1, 2025

Osteoarthritis (OA) constitutes a widespread degenerative joint disease predominantly affecting the elderly, leading to disability. There is still lack of biomarkers for OA, so it cannot be intervened in time. OA were identified from human cartilage datasets using LASSO and SVM-RFE, followed by ROC analysis. LOXL1 was prioritized further research due its high expression robust predictive performance. Anterior cruciate ligament transection (ACLT) surgery-induced rats used explore correlation between inflammatory factors macrophages. Macrophage markers cytokine secretion detected macrophages treated with LOXL1, or co-cultured chondrocytes after siRNA silencing. Five hub OA-specific identified. Elevated correlated IL-6 IL-8 patients increased M1 rats. LOXL1-stimulated upregulated CD86 cytokines. Silencing reduced CD86, cytokines, NF-κB p65 p-STAT3 macrophages, mitigating MMP13 chondrocyte apoptosis. STAT3 signal inhibition reduces p-STAT3, p-p65, IL-1β This study underscores pivotal role activating through signaling, thereby promoting pro-inflammatory contributing pathogenesis. holds promise as potential marker early diagnosis inflammation novel therapeutic target.

Язык: Английский

Comprehensive multiomics analysis identifies PYCARD as a key pyroptosis-related gene in osteoarthritis synovial macrophages

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Март 24, 2025

Background Osteoarthritis (OA) is a chronic joint disease that significantly impairs quality of life. Synovitis plays pivotal role in OA progression, and pyroptosis, form programmed cell death associated with innate immune inflammation, may contribute to the pathogenesis synovitis. Nevertheless, precise pyroptosis remains poorly understood. Methods We performed an analysis bulk RNA sequencing data examine expression profiles pyroptosis-related genes synovium. A LASSO-Cox regression model was employed identify genes. Single-cell were used validate these specific synovial clusters. Differentially expressed (DEGs) macrophages high or low levels core subjected enrichment analysis. protein-protein interaction (PPI) network constructed hub genes, potential therapeutic compounds predicted. Consensus clustering correlations between status. After identifying PYCARD as gene macrophages, we assessed synovium validated its related M1 macrophages. Results total twenty DEGs identified, six selected through LASSO regression. identified key Furthermore, 57 targeting Validation confirmed upregulation Conclusion identified. This study offers valuable insights into treatment targets for OA.

Язык: Английский

Cascade-Targeting Hydrogel Microspheres with Biomimetic Nanoparticles Enable Multifaceted Anti-Inflammatory and Antioxidant Defense for Osteoarthritis Management

Опубликована: Янв. 1, 2025

Язык: Английский