Andrographolide Ameliorates Inflammatory Changes Induced by D-Lactate in Bovine Fibroblast-like Synoviocytes DOI Creative Commons
Stefanie Teuber,

Carolina Manosalva,

Pablo Alarcón

et al.

Animals, Journal Year: 2024, Volume and Issue: 14(6), P. 936 - 936

Published: March 19, 2024

During acute ruminal acidosis, the manifestation of aseptic polysynovitis and lameness in cattle has been observed. Evidence suggests that joint inflammation can be attributed to metabolic alterations induced by D-lactate fibroblast-like synoviocytes (FLSs). We aimed investigate whether andrographolide could mitigate bovine (bFLSs). To assess this, bFLSs were cultured presence or absence andrographolide. evaluated its potential interference with expression proinflammatory cytokines, COX-2, HIF-1α, LDHA using RT-qPCR. Furthermore, we investigated PI3K/Akt signaling IκBα degradation through immunoblotting flow cytometry, respectively. Our observations revealed reduced elevation IL-6, IL-8, D-lactate. Additionally, demonstrated NF-κB pathways bFLSs. In conclusion, our findings suggest potentially reverse inflammatory effects changes bFLSs, showing promise as a therapeutic intervention for managing these conditions associated lameness.

Language: Английский

Failure of cartilage regeneration: emerging hypotheses and related therapeutic strategies DOI
Sathish Muthu, Jasmijn V. Korpershoek, Emanuel J. Novais

et al.

Nature Reviews Rheumatology, Journal Year: 2023, Volume and Issue: 19(7), P. 403 - 416

Published: June 9, 2023

Language: Английский

Citations

122
Andrographolide regulates H3 histone lactylation by interfering with p300 to alleviate aortic valve calcification DOI
Chunli Wang, Shunshun Wang, Zijun Wang

et al.

British Journal of Pharmacology, Journal Year: 2024, Volume and Issue: 181(12), P. 1843 - 1856

Published: Feb. 20, 2024

Abstract Background and Purpose Our previous studies have found that andrographolide (AGP) alleviates calcific aortic valve disease (CAVD), but the underlying mechanism is unclear. This study explores molecular target signal mechanisms of AGP in inhibiting CAVD. Experimental Approach The anti‐calcification effects with treatment were evaluated by alizarin red staining vitro ultrasound histopathological assessment a high‐fat (HF)‐fed ApoE −/− mouse calcification model. A correlation between H3 histone lactylation (H3Kla) was detected. Molecular docking surface plasmon resonance (SPR) experiments further used to confirm p300 as for AGP. Overexpression (oe) silencing (si) verify inhibitory effect targeting on H3Kla ex vivo. Key Results significantly inhibited calcium deposition interstitial cells (VICs) ameliorated calcification. multi‐omics analysis revealed glycolysis pathway involved CAVD, indicating interfered lactate production regulating dehydrogenase (LDHA). In addition, lactylation, new post‐translational modification, shown role promoting Furthermore, H3K9la site correlate Runx2 expression inhibition treatment. Importantly, we transferase H3Kla. Conclusions Implications findings, first time, demonstrated interfering via p300, which might be powerful drug prevent

Language: Английский

Citations

33
The metabolic characteristics and changes of chondrocytes in vivo and in vitro in osteoarthritis DOI Creative Commons

Miradj Siddick Adam,

Huangming Zhuang,

Xunshan Ren

et al.

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 15

Published: May 24, 2024

Osteoarthritis (OA) is an intricate pathological condition that primarily affects the entire synovial joint, especially hip, hand, and knee joints. This results in inflammation synovium osteochondral injuries, ultimately causing functional limitations joint dysfunction. The key mechanism responsible for maintaining articular cartilage function chondrocyte metabolism, which involves energy generation through glycolysis, oxidative phosphorylation, other metabolic pathways. Some studies have shown chondrocytes OA exhibit increased glycolytic activity, leading to elevated lactate production decreased matrix synthesis. In cartilage, display alterations mitochondrial such as ATP stress, can contribute deterioration. Chondrocyte metabolism also anabolic processes extracellular substrate generation. During OA, undergo considerable changes different aspects, homeostasis Numerous been carried out provide tangible therapies by using various models vivo vitro targeting although there are still certain limitations. With growing evidence indicating essential role of disease etiology, this literature review explores characteristics presence both . To insight into complex reprogramming crucial during progression, we investigate dynamic interaction between pathways, lipid function. addition, highlights prospective future research directions novel approaches diagnosis treatment. Adopting a multifaceted strategy, our aims offer comprehensive understanding intricacies within with ultimate goal identifying therapeutic targets capable modulating treatment OA.

Language: Английский

Citations

18
Exploring the diverse role of pyruvate kinase M2 in cancer: Navigating beyond glycolysis and the Warburg effect DOI

Saurabh Upadhyay,

Shumayila Khan, Md. Imtaiyaz Hassan

et al.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2024, Volume and Issue: 1879(3), P. 189089 - 189089

Published: March 6, 2024

Language: Английский

Citations

17
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
Inflammatory and Metabolic Signaling Interfaces of the Hypertrophic and Senescent Chondrocyte Phenotypes Associated with Osteoarthritis DOI Open Access

Emöke Horváth,

Árpád Sólyom,

János Székely

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(22), P. 16468 - 16468

Published: Nov. 17, 2023

Osteoarthritis (OA) is a complex disease of whole joints with progressive cartilage matrix degradation and chondrocyte transformation. The inflammatory features OA are reflected in increased synovial levels IL-1β, IL-6 VEGF, higher TLR-4 binding plasma proteins expression IL-15, IL-18, IL-10 Cox2, cartilage. Chondrocytes undergo hypertrophic senescent transition; these states, the Sox-9, Acan Col2a1 suppressed, whereas RunX2, HIF-2α MMP-13 significantly increased. NF-kB, which triggers many pro-inflammatory cytokines, works BMP, Wnt to link hypertrophy inflammation. Altered carbohydrate metabolism upregulation GLUT-1 contribute formation end-glycation products that trigger inflammation via RAGE pathway. In addition, glycolytic shift, rates oxidative phosphorylation mitochondrial dysfunction generate reactive oxygen species deleterious effects. An important surveyor mechanism, YAP/TAZ signaling system, controls differentiation, inhibits ageing by protecting nuclear envelope suppressing aggrecanases. microenvironment synthesis key components also controlled SIRT1 mTORc. Senescent chondrocytes represent functional end stage differentiation characteristically upregulate p16 p21, but variety chemokines metalloproteinases, developing senescence-associated secretory phenotype. Senolysis dendrobin, miR29b-5p other agents has been shown be efficient under experimental conditions, appears promising tool for treatment OA, as it restores COL2A1 aggrecan synthesis, NF-kB destructive metalloproteinases.

Language: Английский

Citations

26
Natural products in osteoarthritis treatment: bridging basic research to clinical applications DOI Creative Commons

Shunzheng Fang,

Bin Zhang, Wei Xiang

et al.

Chinese Medicine, Journal Year: 2024, Volume and Issue: 19(1)

Published: Feb. 15, 2024

Abstract Osteoarthritis (OA) is the most prevalent degenerative musculoskeletal disease, severely impacting function of patients and potentially leading to disability, especially among elderly population. Natural products (NPs), obtained from components or metabolites plants, animals, microorganisms etc., have gained significant attention as important conservative treatments for various diseases. Recently, NPs been well studied in preclinical clinical researches, showing promising potential treatment OA. In this review, we summed up main signaling pathways affected by OA treatment, including NF-κB, MAPKs, PI3K/AKT, SIRT1, other pathways, which are related inflammation, anabolism catabolism, cell death. addition, described therapeutic effects different animal models current studies patients. At last, discussed research directions in-depth analysis mechanisms new application strategies so promote basic transformation future. We hope that review may allow us get a better understanding about bioeffects therapy, ultimately improve effectiveness NPs-based

Language: Английский

Citations

12
The role of targeting glucose metabolism in chondrocytes in the pathogenesis and therapeutic mechanisms of osteoarthritis: a narrative review DOI Creative Commons

Peng Pi,

Liqing Zeng,

Zhipeng Zeng

et al.

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 15

Published: March 6, 2024

Osteoarthritis (OA) is a common degenerative joint disease that can affect almost any joint, mainly resulting in dysfunction and pain. Worldwide, OA affects more than 240 million people one of the leading causes activity limitation adults. However, pathogenesis remains elusive, lack well-established clinical treatment strategies. Recently, energy metabolism alterations have provided new insights into OA. Accumulating evidence indicates glucose plays key role maintaining cartilage homeostasis. Disorders lead to chondrocyte hypertrophy extracellular matrix degradation, promote occurrence development This article systematically summarizes regulatory effects different enzymes factors related OA, as well mechanism potential various substances by affecting metabolism. provides theoretical basis for better understanding progression optimal prevention

Language: Английский

Citations

12
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
Triglyceride-glucose index in the prediction of new-onset arthritis in the general population aged over 45: the first longitudinal evidence from CHARLS DOI Creative Commons
Yang Liu, Junjie Yao,

Xiaona Xue

et al.

Lipids in Health and Disease, Journal Year: 2024, Volume and Issue: 23(1)

Published: March 13, 2024

Abstract Objective Insulin resistance (IR) imposes a significant burden on inflammatory diseases, and the triglyceride-glucose (TyG) index, which is an easily accessible indicator for detecting IR, holds great application potential in predicting risk of arthritis. The aim this study to analyze association between TyG index new-onset arthritis common population aged over 45 using prospective cohort design. Method This population-based involved 4418 participants from China Health Retirement Longitudinal Study (from Wave 1 4). Multivariate logistic regression models were employed investigate arthritis, RCS analyses used non-linear relationships. Moreover, decision trees utilized identify high-risk populations incident Result Throughout 7-year follow-up interval, it was found that 396 (8.96%) developed last quartile group (Q4) presented highest (OR, 1.39; 95% CI, 1.01, 1.91). No dose-response relationship identified ( P overall =0.068, non−linear =0.203). In stratified analysis, we observed BMI ranging 18.5 24 exhibited heightened susceptibility adverse effects developing interaction = 0.035). Conclusion can be as independent start within individuals above general population. Improving glucose lipid metabolism, along with insulin resistance, may play big part improving primary prevention

Language: Английский

Citations

11