ArticleInternational journal of molecular sciences2023
Intra-Articular Lactate Dehydrogenase A Inhibitor Oxamate Reduces Experimental Osteoarthritis and Nociception in Rats via Possible Alteration of Glycolysis-Related Protein Expression in Cartilage Tissue.
Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 22 citations in OpenAlex.
- HK1-LDHA axis feedback regulation promotes histone lactylation of Wnt5a and mediates prenatal acetaminophen-induced susceptibility to osteoarthritis in male offspring.Experimental & molecular medicine · 2026Article
- The emerging role of lactate in skeletal homeostasis and disorders: Integrated mechanisms and translational opportunities.Journal of orthopaedic translation · 2026Review
- Exploring mitochondrial functions and dysfunctions in chondrocytes: toward the identification of novel therapies for osteoarthritis.Bone research · 2026Review
- H3K18 lactylation promotes glycolysis in bladder cancer via inhibiting GNG7 through regulating PI3K-AKT signaling pathway.World journal of surgical oncology · 2026Article
- Dysregulation of the glycolysis-mitochondrial metabolism axis in osteoarthritis: mechanisms and therapeutic implications.Journal of orthopaedic translation · 2026Review
- The role of lactate on arthritis-associated cells: physiology, pathology, and therapeutic strategies.Cellular and molecular life sciences : CMLS · 2026Review
- Article
- Energy crisis and cartilage collapse: metabolic reprogramming of chondrocytes in osteoarthritis.Frontiers in immunology · 2026Review
- New therapeutic target for osteoarthritis: modulating immune-metabolic aberrations and micromilieu remodeling in underlying bone.Frontiers in pharmacology · 2026Review
- HIF-1α-centered metabolic reprogramming in osteoarthritis: cell type-specific effects and intercellular crosstalk among chondrocytes, BMSCs, and macrophages.Frontiers in immunology · 2026Review
- "Gut-Joint Axis" Perspective on Immunometabolic Crosstalk in Osteoarthritis: A Narrative Review of Mechanistic Insights and Targeted Strategies.Journal of inflammation research · 2026Review
- Mitochondrial transplantation for osteoarthritis: from molecular mechanisms to clinical translation.Frontiers in immunology · 2026Review
- Metabolite-neuro-immune relay in chronic pain: spatial-temporal lactate, succinate and itaconate signalling as drivers of glial reprogramming and neuronal sensitisation.Frontiers in pharmacology · 2026Review
- USP32 promotes temporomandibular joint osteoarthritis by modulating PKM2 stability and glycolytic metabolism in chondrocytes.Cell death & disease · 2025Article
- Lactylation: From Molecular Insights to Disease Relevance.Biomolecules · 2025Review
- Association of Endothelial Activation and Stress Index with Risk of Cardiovascular Disease and All-cause Mortality in Patients with Osteoarthritis.Arquivos brasileiros de cardiologia · 2025Article
- Deciphering the Relationship Between Circulating Metabolites and Osteoarthritis: A Comprehensive Genetic Correlation and Mendelian Randomization Studies.International journal of medical sciences · 2025Article
- Article
- Identification of Key Glycolysis-Related Genes in Osteoarthritis and Their Correlation with Immune Infiltration Using Bioinformatics Analysis and Machine Learning.Open access rheumatology : research and reviews · 2025Article
- Andrographolide Ameliorates Inflammatory Changes Induced by D-Lactate in Bovine Fibroblast-like Synoviocytes.Animals : an open access journal from MDPI · 2024Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Osteoarthritis (OA) is the most common form of arthritis and joint disorder worldwide. Metabolic reprogramming of osteoarthritic chondrocytes from oxidative phosphorylation to glycolysis results in the accumulation of lactate from glycolytic metabolite pyruvate by lactate dehydrogenase A (LDHA), leading to cartilage degeneration. In the present study, we investigated the protective effects of the intra-articular administration of oxamate (LDHA inhibitor) against OA development and glycolysis-related protein expression in experimental OA rats. The animals were randomly allocated into four groups: Sham, anterior cruciate ligament transection (ACLT), ACLT + oxamate (0.25 and 2.5 mg/kg). Oxamate-treated groups received an intra-articular injection of oxamate once a week for 5 weeks. Intra-articular oxamate significantly reduced the weight-bearing defects and knee width in ACLT rats. Histopathological analyses showed that oxamate caused significantly less cartilage degeneration in the ACLT rats. Oxamate exerts hypertrophic effects in articular cartilage chondrocytes by inhibiting glucose transporter 1, glucose transporter 3, hexokinase II, pyruvate kinase M2, pyruvate dehydrogenase kinases 1 and 2, pyruvate dehydrogenase kinase 2, and LHDA. Further analysis revealed that oxamate significantly reduced chondrocyte apoptosis in articular cartilage. Oxamate attenuates nociception, inflammation, cartilage degradation, and chondrocyte apoptosis and possibly attenuates glycolysis-related protein expression in ACLT-induced OA rats. The present findings will facilitate future research on LDHA inhibitors in prevention strategies for OA progression.
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