ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026
FSTL1 Orchestrates Metabolic-Epigenetic Crosstalk: Glycolysis-Dependent H3K18 Lactylation Drives Cartilage Fibrosis in Osteoarthritis.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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The trial behind it
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Who cites it
17 citing papers in PubMed.
- Mitochondrial Quality Control in Degenerative Musculoskeletal Diseases: Signaling Networks and Therapeutic Landscapes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Lactate Signal: Modulator of Cellular Energy Production and Anabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Artemotil Attenuates Fibrosis-Associated Chondrocyte Remodelling in Osteoarthritis in Association With STC1-Related TGF-β/SMAD2/3 Signalling.Journal of cellular and molecular medicine · 2026Article
- Piezo1 accelerates osteoarthritis progression via promotion of HBB-dependent oxidative phosphorylation.The Journal of biological chemistry · 2026Article
- The emerging role of lactate in skeletal homeostasis and disorders: Integrated mechanisms and translational opportunities.Journal of orthopaedic translation · 2026Review
- Dysregulation of the glycolysis-mitochondrial metabolism axis in osteoarthritis: mechanisms and therapeutic implications.Journal of orthopaedic translation · 2026Review
- Review
- Lactylation in tissue fibrosis: epigenetic mechanisms, metabolic crosstalk, and therapeutic opportunities.Journal of translational medicine · 2026Review
- Poricoic Acid A Attenuates Osteoarthritis Progression by Stabilizing PTEN and Suppressing PI3K/AKT Signaling.International journal of molecular sciences · 2026Article
- FSTL1 Orchestrates Metabolic-Epigenetic Crosstalk: Glycolysis-Dependent H3K18 Lactylation Drives Cartilage Fibrosis in Osteoarthritis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Investigating the Mechanistic Link Between Lactate-Induced Histone Lactylation and Cellular Senescence in Osteoarthritis Chondrocytes: Implications for Therapy.International journal of biological sciences · 2026Article
- Lactylation in liver fibrosis: from molecular mechanisms to targeted therapeutic strategies.Frontiers in pharmacology · 2026Review
- Immuno-metabolic crosstalk in osteoarthritis: from mechanisms to therapies.Frontiers in immunology · 2026Review
- HIF-1α-centered metabolic reprogramming in osteoarthritis: cell type-specific effects and intercellular crosstalk among chondrocytes, BMSCs, and macrophages.Frontiers in immunology · 2026Review
- Research progress on protein lactylation in female reproductive disease: molecular mechanisms, functions, and therapeutic implications.Frontiers in pharmacology · 2026Review
- Lactate-driven lactylation reprograms chondrocyte fate and joint inflammation in osteoarthritis: linking metabolism with epigenetic regulation.Frontiers in cell and developmental biology · 2026Review
- Mitochondrial-targeted therapy for osteoarthritis: Challenges and opportunities from basic research to clinical translation.Frontiers in immunology · 2026Review
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
The progression of osteoarthritis (OA) is fundamentally characterized by the aberrant transformation of chondrocytes into a fibrotic phenotype, although the precise molecular mechanisms involved remain inadequately understood. In this study, the interplay between epigenetic modifications and metabolic reprogramming during the activation of fibrocartilage cells in osteoarthritis was investigated. The findings demonstrate that FSTL1 markedly upregulates key glycolytic enzymes, including LDHA, HK2, and PKM, in chondrocytes, triggering a "glycolytic burst" that results in elevated intracellular lactate levels. This accumulated lactate acts as a precursor for epigenetic modifications, specifically promoting the lactylation of histone H3 lysine 18 (H3K18la) in fibrocartilage cells, thereby facilitating the transcriptional activation of critical fibrosis-related genes such as Itga6, Cxcl10, and Parp16. Notably, pharmacological inhibition of the PI3K/mTOR pathway or lactate dehydrogenase significantly diminishes H3K18la levels and markers of chondrocyte fibrosis, while exogenous lactate supplementation can counteract this effect. In summary, this study unveils the core mechanism by which FSTL1 reshapes the epigenetic landscape of chondrocytes and drives the fibrotic process through the activation of the "glycolysis-lactate-H3K18la" cascade axis, offering a dual-target intervention strategy for OA involving metabolic reprogramming and epigenetic modification.
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Registered trials
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