Identification of ZNF652 as a Diagnostic and Therapeutic Target in Osteoarthritis Using Machine Learning DOI Creative Commons
Yeping Chen,

Rongyuan Liang,

Xifan Zheng

et al.

Journal of Inflammation Research, Journal Year: 2024, Volume and Issue: Volume 17, P. 10141 - 10161

Published: Dec. 1, 2024

Purpose: Osteoarthritis (OA) is the most common degenerative joint disease. However, its etiology remains largely unknown. Zinc Finger Protein 652 (ZNF652) a transcription factor implicated in various biological processes. Nevertheless, role OA has not been elucidated. Methods: The search term "osteoarthritis" was utilized to procure transcriptome data relating patients and healthy people from Gene Expression Omnibus (GEO) database. Then screening process initiated identify differentially expressed genes (DEGs). DEGs were discerned using three distinct machine learning methods. accuracy of these diagnosing evaluated Receiver Operating Characteristic (ROC) Curve. A competitive endogenous RNA (ceRNA) visualization network established delve into potential regulatory targets. ZNF652 expression confirmed cartilage rats quantitative reverse polymerase chain reaction (qRT-PCR) Western blotting (WB) analyzed an independent t -test. Results: identified as DEG exhibited highest diagnostic value for according ROC analysis. GO KEGG enrichment analyses suggest that plays vital development through processes including nitric oxide anabolism, macrophage proliferation, immune response, PI3K/Akt MAPK signaling pathways. increased validated qRT-PCR (1.193 ± 0.005 vs 1.000 0.005, p < 0.001) WB (0.981 0.055 0.856 0.026, = 0.012) Conclusion: found be related pathogenesis can potentially serve therapeutic target OA. underlying mechanism pathways, cells their functions findings need clinical trials molecular requires further study. Keywords: osteoarthritis, zinc finger protein 652, algorithms, cell

Language: Английский

NLRP3 overexpression exacerbated synovium tissue degeneration in juvenile collagen-induced arthritis DOI Creative Commons
Fater A. Khadour, Younes A. Khadour, Tao Xu

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 27, 2025

Juvenile idiopathic arthritis (JIA) can lead to synovial inflammation. JIA is a chronic autoimmune inflammatory condition that primarily affects children. It recognized as the most prevalent form of in pediatric population and associated with significant impairment disability. As an regulator, Nod-like receptor 3 (NLRP3) has been implicated various diseases. However, specific mechanism by which NLRP3 impacts progress remains unclear. Therefore, we conducted this study investigate on inflammation juvenile collagen-induced (CIA). The CIA model was established using Sprague‒Dawley (SD) rats aged 2–3 weeks. In study, investigated potential role regulating NLRP3–NF-κB axis rats. To verify effect JIA, expression knocked down or overexpressed adeno-associated virus injected into knee joint observed plays important development CIA, knocking inhibited alleviated synovium We also demonstrated increased tissue, could upregulate NF-κB signal pathway influence Moreover, found increases impairs autophagy capacity activation pyroptosis results interferes CIA. These provide new insight suggest targeting inflammasome may represent promising therapeutic strategy for managing JIA.

Language: Английский

Citations

1
The Interplay of Aging and PANoptosis in Osteoarthritis Pathogenesis: Implications for Novel Therapeutic Strategies DOI Creative Commons

Shaoshan Liu,

Guifeng Zhang, Nan Li

et al.

Journal of Inflammation Research, Journal Year: 2025, Volume and Issue: Volume 18, P. 1951 - 1967

Published: Feb. 1, 2025

Abstract: Osteoarthritis (OA) is a common degenerative joint disease characterized by the progressive degradation of articular cartilage, synovial inflammation, and subchondral bone remodeling. This review explores interplay between aging, PANoptosis, inflammation in OA progression. Age-related cellular immune dysfunctions, including senescence, senescence-associated secretory phenotypes (SASPs), immunosenescence, significantly contribute to degeneration. In OA, dysregulated apoptosis, necroptosis, pyroptosis, particularly chondrocytes, exacerbate cartilage damage. Apoptosis, mediated JNK pathway, reduces chondrocyte density, while necroptosis involving RIPK-1/RIPK-3 NLRP3 inflammasome, respectively, amplify destruction. Inflammatory cytokines damage-associated molecular patterns (DAMPs) further enhance these PANoptotic pathways. Current therapeutic strategies primarily focus on anti-inflammatory agents such as non-steroidal drugs (NSAIDs) corticosteroids, with growing interest anti-senescence targeting senescence SASP. Additionally, exploring PANoptosis mechanisms offers potential for innovative treatments. Keywords: osteoarthritis,

Language: Английский

Citations

0
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

Citations

0
Pyroptosis for osteoarthritis treatment: insights into cellular and molecular interactions inflammatory DOI Creative Commons
Minghui Lin, Cunxin Zhang, Haiming Li

et al.

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

Published: April 1, 2025

Osteoarthritis (OA) is a widely prevalent chronic degenerative disease often associated with significant pain and disability. It characterized by the deterioration of cartilage extracellular matrix (ECM), synovial inflammation, subchondral bone remodeling. Recent studies have highlighted pyroptosis-a form programmed cell death triggered inflammasome-as key factor in sustaining inflammation. Central to this process are inflammatory cytokines interleukin-1β (IL-1β) interleukin-18 (IL-18), which play crucial roles mediating intra-articular pyroptosis through NOD-like receptor protein 3 (NLRP3) inflammasome. This paper investigates role pathway perpetuating diseases its linkage OA. Furthermore, it explores mechanisms pyroptosis, mediated nuclear κB (NF-κB), purinergic P2X ligand-gated ion channel 7 (P2X7R), adenosine monophosphate (AMP)-activated kinase (AMPK), hypoxia-inducible factor-1α (HIF-1α). Additionally, examines interactions among various cellular components context These insights indicate that targeting regulation presents promising therapeutic approach for prevention treatment OA, offering valuable theoretical perspectives effective management.

Language: Английский

Citations

0
Isoliensinine suppresses chondrocytes pyroptosis against osteoarthritis via the MAPK/NF-κB signaling pathway DOI
Zhengze Zhang, Jie Ma,

Yanzi Yi

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 143, P. 113589 - 113589

Published: Nov. 15, 2024

Language: Английский

Citations

3
Tetrahedral Framework Nucleic Acid‐Based Delivery of Astaxanthin Suppresses Chondrocyte Pyroptosis and Modulates Oxidative Stress for the Treatment of Osteoarthritis DOI
Yifan Li, Jiafeng Li, Sheng Xu

et al.

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: 13(28)

Published: June 24, 2024

Worldwide, osteoarthritis (OA) is regarded as the most widespread, distressing, and limiting chronic disease that affects degenerative joints. Currently, there no treatment available to modify progression of OA. The pathogenesis OA significantly linked with oxidative stress pyroptosis. Astaxanthin (Ast) a natural ketocarotenoid pigment potent antioxidant activity shown effectively alleviate cartilage damage in However, its bioavailability greatly limited due poor water solubility, high sensitivity light, temperature, pH. In this study, Ast-loaded tetrahedral framework nucleic acids (tFNAs) or tFNA/Ast complexes (TAC) for Ast delivery are developed. Compared free tFNA alone, TAC exhibits improved drug stability cellular uptake. Most importantly, protects chondrocytes against stress-induced pyroptosis while promoting extracellular matrix anabolism by chondrocytes, ultimately alleviates mouse destabilization medial meniscus (DMM) model. Thus, holds great promise patients.

Language: Английский

Citations

2
Non-apoptotic cell death in osteoarthritis: Recent advances and future DOI Open Access
Pengfei Ji, Ziyu Zhou, Jinyuan Zhang

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 179, P. 117344 - 117344

Published: Aug. 27, 2024

Osteoarthritis (OA) is the most common degenerative joint disease. Multiple tissues are altered during development of OA, resulting in pain and permanent damage to osteoarticular joints. Current research has demonstrated that non-apoptotic cell death plays a crucial role OA. With continuous targeted therapies, shown great potential prevention treatment We systematically reviewed progress on pathogenesis, development, outcome including autophagy, pyroptosis, ferroptosis, necroptosis, immunogenic death, parthanatos. This article reviews mechanism OA provides theoretical basis for identification new targets treatment.

Language: Английский

Citations

1
Collagen hydrogel-driven pyroptosis suppression and combined microfracture technique delay osteoarthritis progression DOI
Jinzhi Meng,

Jinfeng Lu,

Cancai Jiang

et al.

Biomaterials, Journal Year: 2024, Volume and Issue: 314, P. 122817 - 122817

Published: Sept. 7, 2024

Language: Английский

Citations

1
Development and Validation of Diagnostic Models for Transcriptomic Signature Genes for Multiple Tissues in Osteoarthritis DOI Creative Commons

Qichang Gao,

Yiming Ma,

Tuo Shao

et al.

Journal of Inflammation Research, Journal Year: 2024, Volume and Issue: Volume 17, P. 5113 - 5127

Published: July 1, 2024

Background: Progress in research on expression profiles osteoarthritis (OA) has been limited to individual tissues within the joint, such as synovium, cartilage, or meniscus. This study aimed comprehensively analyze common gene characteristics of various structures OA and construct a diagnostic model. Methods: Three datasets were selected: meniscus, knee joint cartilage. Modular clustering differential analysis genes used for further functional analyses construction protein networks. Signature with highest potential identified verified using external datasets. The these was validated clinical samples by Real-time (RT)-qPCR immunohistochemistry (IHC) staining. investigated status immune cells examining their infiltration. Results: merged dataset included 438 DEGs clustered into seven modules WGCNA. intersection WGCNA 190 genes. Using Least Absolute Shrinkage Selection Operator (LASSO) Random Forest algorithms, nine signature ( CDADC1, PPFIBP1, ENO2, NOM1, SLC25A14, METTL2A, LINC01089, L3HYPDH, NPHP3 ), each demonstrating substantial (areas under curve from 0.701 0.925). Furthermore, dysregulation also observed. Conclusion: demonstrated significant efficacy are involved cell Keywords: osteoarthritis, machine learning, infiltration, model

Language: Английский

Citations

0
Therapeutic Framework Nucleic Acid Complexes Targeting Oxidative Stress and Pyroptosis for the Treatment of Osteoarthritis DOI Creative Commons
Jiafeng Li, Yifan Li,

Xiushuai Shang

et al.

Materials Today Bio, Journal Year: 2024, Volume and Issue: 28, P. 101202 - 101202

Published: Aug. 20, 2024

Osteoarthritis (OA) is one of the most prevalent joint diseases and severely affects quality life in elderly population. However, there are currently no effective prevention or treatment options for OA. Oxidative stress pyroptosis play significant roles development progression To address this issue, we have developed a novel therapeutic approach OA that targets oxidative pyroptosis. We synthesized tetrahedral framework nucleic acid (tFNAs) to form complexes (TNCs), which facilitate delivery naturally occurring polymethoxyflavonoid nobiletin (Nob) chondrocytes. TNC has demonstrated favorable bioavailability, stability, biosafety delivering Nob. Both

Language: Английский

Citations

0