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

Zihao Yao,

Yuexin Li, H. Mai

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 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.

Language: Английский

Knee Osteoarthritis: Epidemiology, Pathogenesis, and Mesenchymal Stem Cells: What Else Is New? An Update DOI Open Access
Riccardo Giorgino, Domenico Albano, Stefano Fusco

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(7), P. 6405 - 6405

Published: March 29, 2023

Osteoarthritis (OA) is a chronic disease and the most common orthopedic disorder. A vast majority of social OA burden related to hips knees. The prevalence knee varied across studies such differences are reflected by heterogeneity data reported conducted worldwide. complete understanding pathogenetic mechanisms underlying this pathology essential. inflammatory process starts in synovial membrane with activation immune system, involving both humoral cellular mediators. crucial role played so-called “damage-associated molecular patterns” (DAMPs). Mesenchymal stem cells (MSCs) may be promising option among all possible therapeutic options. However, many issues still debated, as best cell source, their nature, right amount. Further needed clarify remaining doubts. This review provides an overview recent relevant on mechanism cartilage damage OA, including current approaches regenerative medicine.

Language: Английский

Citations

161
Obesity, Metabolic Syndrome, and Osteoarthritis—An Updated Review DOI
Samuel Joshua Pragasam Sampath, Vijayalakshmi Venkatesan, Sudip Ghosh

et al.

Current Obesity Reports, Journal Year: 2023, Volume and Issue: 12(3), P. 308 - 331

Published: Aug. 14, 2023

Language: Английский

Citations

52
M2 macrophage-derived exosomal miR-26b-5p regulates macrophage polarization and chondrocyte hypertrophy by targeting TLR3 and COL10A1 to alleviate osteoarthritis DOI Creative Commons

Yufan Qian,

Genglei Chu, Lei Zhang

et al.

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

Published: Feb. 19, 2024

Osteoarthritis (OA) is one of the most prevalent chronic musculoskeletal diseases among elderly population. In this study, macrophage-derived exosomes were isolated and identified. Exosomes subjected to microRNA (miRNA) sequencing bioinformatic analysis, differentially expressed miRNAs verified. miR-26b-5p target genes confirmed through target-site mutation combined with a dual-luciferase reporter assay. The effects on macrophage polarization chondrocyte hypertrophy assessed in vitro. agomir was applied mice OA induced by anterior cruciate ligament transection (ACLT). therapeutic evaluated via pain behavior experiments histological observations. vitro, repolarized M1 macrophages an anti-inflammatory M2 type targeting TLR3 signaling pathway. could COL10A1, further inhibiting macrophage-conditioned medium (M1-CM). vivo, ameliorated gait abnormalities mechanical allodynia mice. treatment attenuated synovitis cartilage degeneration, thereby delaying progression. conclusion, exosomal protect articular ameliorate COL10A1. affected hypertrophy. Thus, miR-26b-5p-based strategy might be potential method for treatment.

Language: Английский

Citations

24
Self‐Reinforced MOF‐Based Nanogel Alleviates Osteoarthritis by Long‐Acting Drug Release DOI

Yun Sun,

Shenglong Ding, Xiyuan Zhao

et al.

Advanced Materials, Journal Year: 2024, Volume and Issue: unknown

Published: April 29, 2024

Abstract Intra‐articular injection of drugs is an effective strategy for osteoarthritis (OA) treatment. However, the complex microenvironment and limited joint space result in rapid clearance drugs. Herein, a nanogel‐based proposed prolonged drug delivery remodeling. Nanogel constructed through functionalization hyaluronic acid (HA) by amide reaction on surface Kartogenin (KGN)‐loaded zeolitic imidazolate framework‐8 (denoted as KZIF@HA). Leveraging inherent hydrophilicity HA, KZIF@HA spontaneously forms nanogels, ensuring extended release OA microenvironment. exhibits sustained over one month, with low leakage risk from cavity compared to KZIF, enhanced cartilage penetration, reparative effects chondrocytes. Notably, KGN released serves promote extracellular matrix (ECM) secretion hyaline regeneration. Zn 2+ reverses progression promoting M2 macrophage polarization establish anti‐inflammatory Ultimately, facilitates regeneration alleviation within three months. Transcriptome sequencing validates that stimulates macrophages secretes IL‐10 inhibit JNK ERK pathways, chondrocytes recovery enhancing ECM This pioneering nanogel system offers new therapeutic opportunities release, presenting significant stride treatment strategies.

Language: Английский

Citations

21
Opsonization Inveigles Macrophages Engulfing Carrier‐Free Bilirubin/JPH203 Nanoparticles to Suppress Inflammation for Osteoarthritis Therapy DOI Creative Commons
Huirong Huang,

Shimin Zheng,

Jianing Wu

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(22)

Published: April 9, 2024

Abstract Osteoarthritis (OA) is a chronic inflammatory disease characterized by cartilage destruction, synovitis, and osteophyte formation. Disease‐modifying treatments for OA are currently lacking. Because inflammation mediated an imbalance of M1/M2 macrophages in the synovial cavities contributes to progression, regulating M1 M2 polarization can be potential therapeutic strategy. Basing on inherent immune mechanism pathological environment OA, immunoglobulin G‐conjugated bilirubin/JPH203 self‐assembled nanoparticle (IgG/BRJ) developed, its evaluated. After intra‐articular administration, IgG conjugation facilitates recognition engulfment nanoparticles macrophages. The internalized disassemble response increased oxidative stress, released bilirubin (BR) JPH203 scavenge reactive oxygen species (ROS), inhibit nuclear factor kappa‐B pathway, suppress activated mammalian target rapamycin result repolarization enhance M2/M1 ratios. Suppression IgG/BRJ promotes protection repair rat model, thereby improving outcomes. This strategy opsonization involving engulf carrier‐free BR/JPH203 therapy holds great intervention treatment.

Language: Английский

Citations

20
Metabolic reprogramming of macrophages by a nano-sized opsonization strategy to restore M1/M2 balance for osteoarthritis therapy DOI
Ruijie Chen,

Shimin Zheng,

Xinyu Zhao

et al.

Journal of Controlled Release, Journal Year: 2025, Volume and Issue: 380, P. 469 - 489

Published: Feb. 11, 2025

Language: Английский

Citations

2
Revolutionizing osteoarthritis treatment: How mesenchymal stem cells hold the key DOI Open Access

Ruijiao Tian,

Shibo Su,

Yu Yang

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 173, P. 116458 - 116458

Published: March 19, 2024

Osteoarthritis (OA) is a multifaceted disease characterized by imbalances in extracellular matrix metabolism, chondrocyte and synoviocyte senescence, as well inflammatory responses mediated macrophages. Although there have been notable advancements pharmacological surgical interventions, achieving complete remission of OA remains formidable challenge, oftentimes accompanied significant side effects. Mesenchymal stem cells (MSCs) emerged promising avenue for treatment, given their ability to differentiate into chondrocytes facilitate cartilage repair, thereby mitigating the impact an microenvironment induced This comprehensive review aims provide concise overview diverse roles played MSCs treatment OA, while elucidating underlying mechanisms behind these contributions. Specifically, include: (a) Promotion regeneration; (b) Inhibition degradation; (c) Attenuating macrophage-induced microenvironment; (d) Alleviation pain. Understanding paramount developing novel therapeutic strategies. By harnessing regenerative potential immunomodulatory properties MSCs, it may be possible devise more effective safer approaches managing OA. Further research clinical studies are warranted optimize utilization realize full field therapeutics.

Language: Английский

Citations

15
Glycolysis: an emerging regulator of osteoarthritis DOI Creative Commons

Dingming Jiang,

Jianan Guo,

Yingquan Liu

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 9, 2024

Osteoarthritis (OA) has been a leading cause of disability in the elderly and there remains lack effective therapeutic approaches as mechanisms pathogenesis progression have yet to be elucidated. As OA progresses, cellular metabolic profiles energy production are altered, emerging reprogramming highlights importance specific pathways disease progression. crucial part glucose metabolism, glycolysis bridges inflammatory dysfunctions. Moreover, glycolytic pathway is involved different areas metabolism inflammation, associated with variety transcription factors. To date, it not fully elucidated whether changes its key enzymes onset or OA. This review summarizes important role mediating inducing tissue inflammation injury, aim providing further insights into pathological functions proposing new targets for treatment

Language: Английский

Citations

11
Apoptotic body-inspired nanotherapeutics efficiently attenuate osteoarthritis by targeting BRD4-regulated synovial macrophage polarization DOI Creative Commons
Yidi Xu,

Xiangchao Liang,

Zhipeng Li

et al.

Biomaterials, Journal Year: 2024, Volume and Issue: 306, P. 122483 - 122483

Published: Jan. 27, 2024

Language: Английский

Citations

11
The role of macrophage polarization in rheumatoid arthritis and osteoarthritis: Pathogenesis and therapeutic strategies DOI

Jun‐Way Chang,

Chih‐Hsin Tang

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 142, P. 113056 - 113056

Published: Aug. 31, 2024

Language: Английский

Citations

9