Precisely Regulating M2 Subtype Macrophages for Renal Fibrosis Resolution

ACS Nano, Год журнала: 2023, Номер 17(22), С. 22508 - 22526

Опубликована: Ноя. 10, 2023

Macrophages are central to the pathogenesis of kidney disease and serve as an effective therapeutic target for injury fibrosis. Among them, M2-type macrophages have double-edged effects regarding anti-inflammatory tissue repair. Depending on polarization M2 subtypes (M2a or M2c) in diseased microenvironment, they can either mediate normal repair drive In renal fibrosis, M2a promotes progression through macrophage-to-myofibroblast transition (MMT) cells, while M2c possesses potent functions repair, is inhibited. The mechanisms underlying this differentiation complex currently not well understood. Therefore, study, we first confirmed that M2a-derived MMT cells responsible development fibrosis demonstrated intensity TGF-β signaling a major factor determining differential M2c. Under excessive stimulation, undergoes process known whereas moderate stimulation favors phenotype macrophages. Based these findings, employed targeted nanotechnology codeliver endoplasmic reticulum stress (ERS) inhibitor (Ceapin 7, Cea C) conventional glucocorticoids (Dexamethasone, Dex D), precisely modulating ATF6/TGF-β/Smad3 axis within This approach calibrated level macrophages, promoting their toward suppressing polarization. study indicates combination ERS first-line drug holds promise resolution.

Язык: Английский

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MiR-370-3p regulate TLR4/SLC7A11/GPX4 to alleviate the progression of glucocorticoids-induced osteonecrosis of the femoral head by promoting osteogenesis and suppressing ferroptosis

Journal of Orthopaedic Translation, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Язык: Английский

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Targeting different phenotypes of macrophages: A potential strategy for natural products to treat inflammatory bone and joint diseases

Phytomedicine, Год журнала: 2023, Номер 118, С. 154952 - 154952

Опубликована: Июль 12, 2023

Язык: Английский

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Construction of oxidized icariin functionalized collagen composite with promoting osteogenesis, vascularization and anti-inflammatory properties potential for bone repair application

European Polymer Journal, Год журнала: 2024, Номер 205, С. 112755 - 112755

Опубликована: Янв. 9, 2024

Язык: Английский

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Early depletion of M1 macrophages retards the progression of glucocorticoid-associated osteonecrosis of the femoral head

International Immunopharmacology, Год журнала: 2023, Номер 122, С. 110639 - 110639

Опубликована: Июль 21, 2023

Inflammation stands as a pivotal factor in the pathogenesis of glucocorticoid-associated osteonecrosis femoral head (GA-ONFH). However, vital role played by M1 macrophages, principal constituents inflammatory process, remains largely underexplored. In this study, we employed reverse transcription-quantitative polymerase chain Reaction (RT-PCR), western blot, and flow cytometry to assess impact M1-conditioned medium on cultures mouse bone marrow-derived mesenchymal stem cells (BMSCs) Murine Long Osteocyte-Y4 (MLO-Y4) vitro. Moreover, quantified levels cytokines through employment an enzyme-linked immunosorbent assay (ELISA). For vivo analysis, examined macrophages investigated NF-kB signaling pathway specimens obtained from heads animals humans. We found that number GA-ONFH patients grew significantly, mice remarkably increase, maintaining high intramedullary. vitro, macrophage-conditioned elicited apoptosis BMSCs MLO-Y4 cells, shedding light intricate interplay between these cell types. The presence TNF-α within activated NF-κB pathway, providing mechanistic insight into apoptotic induction. employing robust rat macrophage clearance model model, demonstrated remarkable attenuation expression subsequent clearance. This pronounced reduction engenders diminished cellular decelerated trajectory progression. conclusion, our study reveals crucial involvement GA-ONFH, highlighting their indispensable disease Furthermore, early emerges promising strategy for impeding development GA-ONFH.

Язык: Английский

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Potential mechanisms of rheumatoid arthritis therapy: Focus on macrophage polarization

International Immunopharmacology, Год журнала: 2024, Номер 142, С. 113058 - 113058

Опубликована: Сен. 4, 2024

Язык: Английский

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Novel Clinical Insights into the Pathogenesis of Posttraumatic Elbow Stiffness: An Expression Profile Analysis of Contracted Joint Capsule in Human

Journal of Inflammation Research, Год журнала: 2025, Номер Volume 18, С. 167 - 182

Опубликована: Янв. 1, 2025

Posttraumatic elbow stiffness is a complex complication with two characteristics of capsular contracture and heterotopic ossification. Currently, genomic mechanisms pathogenesis posttraumatic remain inadequately understood. This study aims to identify differentially expressed genes (DEGs) elucidate molecular networks stiffness, providing novel insights into disease at transcriptome level. Global sequencing was conducted on six samples from individuals three control fractures. Differentially (DEGs), microRNAs, long non-coding RNAs (LncRNAs) were identified analyzed. Functional enrichment analysis performed, the associated protein-protein interaction (PPI) network constructed. MicroRNAs targeting these DEGs identified, transcription factors (TFs) predicted using ENCODE database. Finally, key validated by quantitative real-time polymerase chain reaction (qRT-PCR). A total 4909 protein-coding, LncRNA microRNA detected, including 2124 upregulated 2785 downregulated. Kyoto Encyclopedia Genes Genomes (KEGG) pathway revealed that significantly enriched in 36 signaling pathways, notably involving inflammatory responses extracellular matrix (ECM) receptor interactions. The highlighted such as SPP1, IBSP, MMP13 MYO1A having higher degrees connectivity. Key microRNAs (hsa-miR-186-5p, hsa-miR-515-5p, hsa-miR-590-3p) (TFDP1 STAT3) be implicated through microRNA-transcription factor regulatory analysis. provided underlying changes contracted capsules stiffness. Hub MMP13, MYO1A, (has-miR-186-5p, has-miR-515-5p, TFs may serve prognostic therapeutic targets provide new idea for future research direction clinical treatment.

Язык: Английский

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Astaxanthin Prevents Glucocorticoid-Induced Femoral Head Osteonecrosis by Targeting Ferroptosis through the JAK2/STAT3 Signaling Pathway

Journal of Agricultural and Food Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Фев. 4, 2025

Glucocorticoid (GC) is extensively used in clinical practice, and the osteonecrosis of femoral head caused by them a common issue orthopedic surgery, yet underlying mechanisms remain unclear. Astaxanthin (AST), potent natural antioxidant, has an unexplored impact on GC-induced (GIONFH). This study explores effects AST counteracting dexamethasone (Dex)-induced ferroptosis GIONFH. We developed rat model GIONFH using intraperitoneal Dex injections conducted vitro analysis culturing osteoblasts (OBs) with treatment. assessed Dex-treated OBs C11-BODIPY FerroOrange staining, mitochondrial functionality tests, protein expression analyses through Western blot immunofluorescence. The influence bone microarchitecture was micro-CT, hematoxylin eosin immunofluorescence, immunohistochemistry at imaging histological levels. Our findings suggest that exerts inhibitory effect Dex-induced In vitro, treatment increased glutathione decreased malondialdehyde, lipid peroxidation, mitochondrial-reactive oxygen species. Additionally, also enhances phosphorylation STAT3, upregulates peroxidase 4 osteogenic-related proteins, stimulates formation. To delve deeper into mechanism, revealed triggered activation JAK2/STAT3 signaling. Moreover, use siRNA-STAT3 blocked beneficial cultivated Dex. brief, combats activating pathway to inhibit ferroptosis.

Язык: Английский

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Crosstalk Between H-Type Vascular Endothelial Cells and Macrophages: A Potential Regulator of Bone Homeostasis

Journal of Inflammation Research, Год журнала: 2025, Номер Volume 18, С. 2743 - 2765

Опубликована: Фев. 1, 2025

The crosstalk between H-type endothelial cells (ECs) and macrophages is critical for maintaining angiogenesis osteogenesis in bone homeostasis. As core components of type H vessels, ECs respond to various pro-angiogenic signals, forming specialized vascular structures characterized by high expression platelet-endothelial cell adhesion molecule-1 (CD31) mucin (EMCN), thereby facilitating angiogenesis-osteogenesis coupling during formation. Macrophages, as key immune the perivascular region, are primarily classified into classically activated pro-inflammatory M1 phenotype selectively anti-inflammatory M2 phenotype, performing dual functions regulating local tissue homeostasis innate immunity. In recent years, complex vessel has garnered significant interest context bone-related diseases. Orderly regulation immunity provides a new direction preventing metabolic disorders such osteoporosis osteoarthritis. However, their interactions remain insufficiently understood, with limited clinical data available. This review comprehensively examines intricate diverse phenotypes, Insights signaling pathways that regulate crosstalk, focusing on roles osteogenesis. Furthermore, discusses interventions targeting this challenges remain. These insights may offer perspectives provide theoretical foundation developing novel therapeutic strategies.

Язык: Английский

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Mechanistic Insights into Salvigenin for Glucocorticoid-Induced Femoral Head Osteonecrosis: A Network Pharmacology and Experimental Study

Biomedicines, Год журнала: 2025, Номер 13(3), С. 614 - 614

Опубликована: Март 3, 2025

Background/Objectives: Glucocorticoid-induced osteonecrosis of the femoral head (GIOFH) is a debilitating condition resulting from impaired bone metabolism and vascular disruption due to prolonged glucocorticoid use. This study aimed explore therapeutic potential salvigenin, flavonoid with antioxidative estrogen-like properties, in alleviating GIOFH by modulating estrogen receptor alpha (ESR1) pathways. Methods: A network pharmacology approach was utilized identify salvigenin’s targets their association GIOFH. Protein–protein interaction networks, along Gene Ontology KEGG pathway analyses, were conducted clarify multi-target mechanisms. Molecular docking dynamics simulations assessed between salvigenin ESR1. Experimental validation included vitro assays on MG63 cells treated dexamethasone (Dex) mimic GIOFH, evaluating oxidative stress, apoptosis, osteogenic differentiation, ESR1 expression. Results: Network analysis identified ESR1, NOS3, MMP9 as key hub salvigenin. confirmed stable binding Salvigenin significantly reduced Dex-induced stress apoptosis osteoblasts while restoring differentiation Functional showed improved mineralized nodule formation, ALP activity, mitochondrial integrity salvigenin-treated cells. Conclusions: exhibits significant addressing through ESR1-mediated These results offer strong foundation for future translational studies development salvigenin-based therapies glucocorticoid-induced disorders.

Язык: Английский

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