Role of macrophage in intervertebral disc degeneration

Bone Research, Journal Year: 2025, Volume and Issue: 13(1)

Published: Jan. 23, 2025

Language: Английский

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Targeting FAP-positive chondrocytes in osteoarthritis: a novel lipid nanoparticle siRNA approach to mitigate cartilage degeneration

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Oct. 26, 2024

Osteoarthritis (OA) is a common joint disease that leads to chronic pain and functional limitations. Recent research has revealed soluble fibroblast activation protein (FAP) secreted from OA synovium could degrade type II collagen (Col2) in cartilage promote the progression of OA. This study aimed reveal role FAP chondrocytes develop novel lipid nanoparticle (LNP)-FAP siRNA delivery system for treatment. The expression knee patients was investigated using [68 Ga]Ga-FAPI-04 PET vivo immunofluorescence, western blotting, RT-qPCR vitro. Cell senescence determined by senescence-associated β-galactosidase (SA-β-Gal) assay after overexpressing or knockdown chondrocytes. An model with chondrocyte-specific knockout mice applied investigate chondrocyte development. therapeutic effects (LNP) @FAP on degeneration were evaluated rat model. Our found higher uptake detected PET/CT scan. mRNA levels highly expressed OA-damaged cartilage. Moreover, we overexpression promotes senescence, genetic alleviates Knockdown alleviate suppress NF-κB pathway reduce secretory phenotype (SASP). In OA, intraarticular injection LNP@FAP can senescent cells ameliorate destruction. FAP-positive play significant pathogenesis Targeting these selectively potential mitigate disease. provides valuable insights into as promising strategy treatment

Language: Английский

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MicroSphere 3D Structures Delay Tissue Senescence through Mechanotransduction

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 9, 2025

The extracellular matrix (ECM) stores signaling molecules and facilitates mechanical biochemical in cells. However, the influence of biomimetic "rejuvenation" ECM structures on aging- degeneration-related cellular activities tissue repair is not well understood. We combined physical extrusion precise "on–off" alternating cross-linking methods to create anisotropic biomaterial microgels (MicroRod MicroSphere) explored how they regulate cell nucleus pulposus (NP) their potential antidegenerative effects intervertebral discs. NP cells exhibited aligned growth along surface MicroRod, enhanced proliferation, reduced apoptosis. This suggests an adaptive response involving adhesion mechanosensing, which causes cytoskeletal extension via environmental cues. maintain nuclear membrane integrity through YAP/TAZ pathway, activates cGAS-STING pathway rectify aging mechanisms. In vivo, MicroRod carries reduces inflammatory factor protease secretion degenerated discs, inhibiting degeneration promoting regeneration. Our findings highlight role stress maintaining activity antiaging harsh environments, providing a foundation for further research development biomaterials.

Language: Английский

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Baicalein-loaded porous silk fibroin microspheres modulate the senescence of nucleus pulposus cells through the NF-κB signaling pathway

Colloids and Surfaces B Biointerfaces, Journal Year: 2025, Volume and Issue: unknown, P. 114537 - 114537

Published: Jan. 1, 2025

Language: Английский

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Integrated bulk and single-cell RNA sequencing to identify potential biomarkers in intervertebral disc degeneration

European journal of medical research, Journal Year: 2025, Volume and Issue: 30(1)

Published: Feb. 14, 2025

Nucleus pulposus (NP) deterioration plays a significant role in the development of intervertebral disc degeneration (IVDD) and low back pain (LBP). This paper aims to identify potential genes within degenerated NP tissue elucidate pathogenesis IVDD through bioinformatics analysis. We conducted transcriptomic analysis patient's degenerative employing advanced techniques machine learning algorithms. Utilizing hdWGCNA, we successfully acquired WGCNA single-cell sequencing data pinpointed crucial implicated IVDD. Subsequently, employed Monocle3 package perform pseudotime sequence analysis, enabling identification associated with differentiation developmental processes tissue. Following this, normalized logarithmically transformed bulk data. preliminary screening using single-factor logistic regression on derived from sequencing. Next, applied two techniques, namely, SVM–RFE random forest, discern pivotal pathogenic genes. Finally, used validation sets verify trends qualitativeness performed vitro vivo analyses normal tissues. 909 were identified while uncovered 1964 related processes. The had 208 common. an initial by integrating database single regression. utilized CDH, DPH5, SELENOF. PCR confirmed that expression CDH DPH5 degraded nucleus cells (NPCs) was decreased 31% 28% vivo, 36% 29% vitro, respectively, SELENOF showed opposite trend. Furthermore, validated imaging histological staining. As IVDD, our findings indicate CTH, are important players might be promising therapeutic targets for treatment.

Language: Английский

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MiRNA Let-7i-5p-Contained Small Extracellular Vesicles from Macrophages Induce Nucleus Pulposus Cell Senescence via Targeting LIN28A

International Journal of Nanomedicine, Journal Year: 2025, Volume and Issue: Volume 20, P. 2163 - 2179

Published: Feb. 1, 2025

To investigate the role of macrophage-derived small extracellular vesicles (MΦ-sEVs) in nucleus pulposus (NP) cell (NPC) senescence and screen pro-senescent micro-RNA (miRNA) MΦ-sEVs potential mRNA targets. Bone marrow-derived macrophage (BMDM)-derived sEVs were isolated by differential centrifugation, phenotypes identified. NPCs treated with MΦ-sEVs, cellular levels examined senescence-associated β-galactosidase (SA‑β‑Gal) staining Western blotting (WB). Activation secretory phenotype (SASP) was tested using qRT-PCR cytometric bead arrays (CBA). LPS+IFNγ-MΦ-sEVs or IL-4-MΦ-sEVs injected into rat coccygeal NP tissues to determine vivo effects on intervertebral disc degeneration (IVDD) NPC senescence. The miRNA evaluated PANDORA sequencing. transfected mimics inhibitors miRNAs pro-senescence effects. displayed cup-shaped morphology, diameters mainly ranging from 40 200 nm. Both impaired viability accelerated expression SASP senescence-related proteins, including p16, p21, p53, elevated treatment. Animal experiments indicated that exacerbated IVDD increased p16-positive ratio activated SASP. sequencing revealed high let-7i-5p, which exerted downregulating LIN28A expression. Inhibiting silencing C1632 specific siRNAs also triggered induced delivering let-7i-5p inhibit LIN28A.

Language: Английский

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Regulatory Roles of Exosomes in Aging and Aging-Related Diseases

Biogerontology, Journal Year: 2025, Volume and Issue: 26(2)

Published: Feb. 18, 2025

Language: Английский

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Identification of Senescence-Related Genes for the Prediction of Ulcerative Colitis Based on Interpretable Machine Learning Models

Journal of Inflammation Research, Journal Year: 2025, Volume and Issue: Volume 18, P. 3431 - 3447

Published: March 1, 2025

Background: Cellular senescence, a hallmark of aging, significantly contributes to the pathology ulcerative colitis (UC). Despite this, role senescence-related genes in UC remains largely undefined. This study seeks clarify impact cellular senescence on by identifying key and developing diagnostic models with potential clinical utility. Methods: Clinical data gene expression profiles were obtained from Gene Expression Omnibus (GEO) database. Senescence-related differentially expressed (sene-DEGs) between patients healthy controls identified using various bioinformatics techniques. Functional enrichment immune infiltration analyses performed understand subtype characteristics derived sene-DEGs through consensus clustering. Machine learning algorithms employed select feature sene-DEGs, their was validated across multiple independent datasets human specimens. A nomogram incorporating these created assessed, its performance evaluated receiver operating characteristic (ROC) analysis datasets. Results: Fourteen differential controls. These enabled classification into molecular subtypes via unsupervised ABCB1 LCN2 emerged as central hub machine importance analysis. ROC verified value Validation specimens supported findings. Furthermore, levels showed significant associations cell profiles. The logistic regression (LR) model based demonstrated accurate prediction, confirmed curve model, constructed genes, exhibited outstanding prediction capabilities, DCA, C index, calibration assessments. Conclusion: integrated approach biomarkers associated senescence. findings enhance understanding pathogenesis propose valuable biomarker. Keywords: colitis, biomarkers,

Language: Английский

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LT-α Facilitates the Aerobic Glycolysis and M1 Polarization of Macrophages by Activating the NF-κB Signaling Pathway in Intervertebral Disc Degeneration

Journal of Inflammation Research, Journal Year: 2025, Volume and Issue: Volume 18, P. 4103 - 4120

Published: March 1, 2025

Injury and inflammatory activate polarize macrophages in intervertebral disc degeneration (IVDD). Further research needs to be carried explore the mechanisms that regulate macrophage polarization, providing new insights targets for IVDD treatment. The aim of our study was evaluate influence LT-α on aerobic glycolysis (AG) polarization macrophages. M0 were achieved by stimulating THP-1 cells with PMA. M1 obtained IFN-γ LPS stimulation Energy metabolomics, AG apoptosis related protein expression, migration invasion measurement, proliferation analyzed. Polarization macrophages, associated genes recruitment evaluated. NF-κB signaling ascertained laser confocal Western blotting. propanoate metabolism pathway enriched overexpressing various energy metabolites detected. Glucose absorption, lactic acid production, levels proteins strikingly increased overexpression remarkably repressed knockdown accompanied activated inactivated signaling, respectively. Suppressed ability, restrained proliferation, AG, enhanced observed nucleus pulposus (NP) treated overexpressed reduced recruitment, opposite results when abolished co-culturing inhibitor. facilitates via activating pathway.

Language: Английский

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Cartilage Endplate‐Targeted Engineered Exosome Releasing and Acid Neutralizing Hydrogel Reverses Intervertebral Disc Degeneration

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: 14(2)

Published: Nov. 18, 2024

Abstract Cartilage endplate cell (CEPC) and nucleus pulposus (NPC) inflammation are critical factors that contribute to intervertebral disc degeneration (IVDD). Recent evidence indicated iron ion influx, reactive oxygen species (ROS), the cGAS‐STING pathway involved in CEPC inflammatory degeneration. Moreover, cytokines produced by degenerating CEPCs lactic acid accumulation within microenvironment significantly NPC inflammation. Consequently, simultaneous alleviation of correction acidic anticipated reverse IVDD. Herein, CEPC‐targeted engineered exosomes loaded with salvianolic A incorporated into a CaCO 3 /chitosan hydrogel, forming composite gel, CAP‐sEXOs@Gel. Notably, CAP‐sEXOs@Gel shows long local retention, realizes slow release CAP‐sEXOs specific uptake CEPCs. After CEPCs, reduce intracellular ROS inhibiting hypoxia‐inducible factor‐2α (HIF‐2α)/TfR1 expression. Iron influx inhibition maintenance normal mitochondrial function reduced mtDNA leakage, suppresing pathway. Additionally, component neutralizes H + , thereby alleviating Collectively, this novel hydrogel demonstrates ability concurrently inhibit inflammation, presenting promising therapeutic approach for

Language: Английский

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