ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
UGDH Lactylation Aggravates Osteoarthritis by Suppressing Glycosaminoglycan Synthesis and Orchestrating Nucleocytoplasmic Transport to Activate MAPK Signaling.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed.
- Lactylation Remodels Tumorigenesis, Immune Microenvironment, and Therapeutic Response.Current issues in molecular biology · 2026Review
- Endocrine‑metabolic imbalance drives osteoarthritis: From whole‑joint pathobiology to precision therapy (Review).International journal of molecular medicine · 2026Review
- Exercise alleviates age-related osteoarthritis associated with PGC-1α activation to suppress chondrocyte senescence and aberrant glycolysis.Journal of orthopaedic translation · 2026Article
- Targeting UXS1-Dependent Glucuronate Detoxification Potentiates Metformin's Anti-Tumor Efficacy in Lung Adenocarcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Protein lactylation in health and diseases: molecular mechanisms, biological significance, and clinical implications.Signal transduction and targeted therapy · 2026Review
- 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
- Enolase 2-mediated lactylation-dependent disruption of the GNL3-MDM2-p53 axis in age-related osteoarthritis.Cellular & molecular biology letters · 2026Article
- Research progress on cellular senescence in the pathogenesis and treatment of osteoarthritis and temporomandibular joint osteoarthritis.Journal of oral & facial pain and headache · 2026Review
- Cuttlefish ink nanoparticle hydrogels ameliorate osteoarthritis via concurrent inhibition of macrophage pyroptosis and chondrocyte senescence.Journal of nanobiotechnology · 2026Article
- Review
- Beyond a metabolite: lactate and lactylation in lung diseases.Respiratory research · 2026Review
- Oxysophoridine promotes osteoarthritis repair via GSH system activation and ROS suppression.Scientific reports · 2026Article
- FSTL1 Orchestrates Metabolic-Epigenetic Crosstalk: Glycolysis-Dependent H3K18 Lactylation Drives Cartilage Fibrosis in Osteoarthritis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Lactate and Acidification: Emerging Metabolic Regulators of Osteoarthritis.Current medical science · 2026Review
- [Research progress on lactylation modification in pathogenesis of osteoarthritis].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2026Review
- Energy crisis and cartilage collapse: metabolic reprogramming of chondrocytes in osteoarthritis.Frontiers in immunology · 2026Review
- Lactate-driven lactylation reprograms chondrocyte fate and joint inflammation in osteoarthritis: linking metabolism with epigenetic regulation.Frontiers in cell and developmental biology · 2026Review
- When metabolic enzymes meet lactylation: a bidirectional dialogue in health and disease.Frontiers in cell and developmental biology · 2026Review
- Integrating single-cell analysis and machine learning algorithms to explore lactylation-related molecular mechanisms and therapeutic responses in clear cell renal cell carcinoma and identifying CDT1 as a potential biomarker.Frontiers in endocrinology · 2026Article
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Osteoarthritis (OA) progression is closely related to dysregulated glycolysis. As the primary metabolite of glycolysis, lactate plays a detrimental role in OA. However, how lactate exacerbates OA process remains unclear. Here, this study revealed that lactate levels are elevated in the synovial fluid of OA patients and IL-1β-treated human primary chondrocytes, promoting protein pan-lactylation. Functionally, hyper-lactylation exacerbates chondrocytes extracellular matrix (ECM) degradation and cell apoptosis in vitro and in vivo. Moreover, UDP-glucose dehydrogenase (UGDH) is proven to be the key lactylated protein in lactate-treated chondrocytes, which undergoes lactylation at lysine 6 (K6). Lactylated UGDH repressed its enzymatic activity, reducing glycosaminoglycan synthesis and disregulating its nuclear-cytoplasmic distribution. Mechanistically, K6 lactylation of UGDH impedes the interaction of UGDH and signal transducer and activator of transcription 1 (STAT1), thus promoting the transcription of mitogen-activated protein kinase kinase kinase 8 (MAP3K8) and activating the MAPK signaling pathway. Importantly, in vitro and in vivo treatment with A485, a specific acyltransferase P300 inhibitor, suppressed UGDH lactylation and rescued chondrocytes ECM degradation and OA progression. These findings uncover a new mechanism underlying OA pathogenesis and highlight the potential of targeting UGDH lactylation as a novel therapeutic strategy for OA.
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Registered trials
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