ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2020
Lactate Dehydrogenase Inhibition With Oxamate Exerts Bone Anabolic Effect.
Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 41 citations in OpenAlex.
- Immunometabolic Modulation of the Bone Marrow Niche by Bioactive Materials to Rescue Impaired Fracture Healing.Stem cell reviews and reports · 2026Review
- Unveiling lactylation: A novel frontier in the pathogenesis of diabetic nephropathy (Review).International journal of molecular medicine · 2026Review
- Regulating Glucose Metabolism Enzymes for Osteoporosis Therapy: Current and Future Approaches.International journal of molecular sciences · 2026Review
- Lactate and lactylation in osteoporosis: pathogenesis, regulation, and future perspectives.Journal of bone and mineral metabolism · 2026Review
- The purinergic receptor P2rx7 mediated ATP sensing is required to prevent bone aging by directing mitochondrial fitness of MSCs.Journal of advanced research · 2026Article
- Histone Lactylation Couples FSH-Driven Lactate Metabolism to Mitochondrial Biogenesis by Enhancing HDAC4-Mediated Deacetylation of PGC-1α in Granulosa Cells.Research (Washington, D.C.) · 2026Article
- Histone lactylation drives METTL3 upregulation-mediated RNA m6A modification of CCT2 to hinder CD8Cellular and molecular life sciences : CMLS · 2025Article
- Oxamate, an LDHA Inhibitor, Inhibits Stemness, Including EMT and High DNA Repair Ability, Induces Senescence, and Exhibits Radiosensitizing Effects in Glioblastoma Cells.International journal of molecular sciences · 2025Article
- Burning lactic acid: a road to revitalizing antitumor immunity.Frontiers of medicine · 2025Review
- Oxamate suppresses whole-body energy metabolism at rest and during exercise in mice by inhibiting fat oxidation and altering lactate dynamics.Physical activity and nutrition · 2025Article
- Bioenergetic programs of cancellous and cortical bone are distinct and differ with age and mechanical loading.Scientific reports · 2025Article
- LDHA-mediated YAP lactylation promotes the tumor progression of hepatocellular carcinoma by inducing YAP dephosphorylation and activation.Biology direct · 2025Article
- Trimethylamine-N-oxide accelerates osteoporosis by PERK activation of ATF5 unfolding.Cellular and molecular life sciences : CMLS · 2024Article
- Synthesis of Ethyl Pyrimidine-Quinolincarboxylates Selected from Virtual Screening as Enhanced Lactate Dehydrogenase (LDH) Inhibitors.International journal of molecular sciences · 2024Article
- Article
- Mitochondrial dysfunction and therapeutic perspectives in osteoporosis.Frontiers in endocrinology · 2024Review
- Mitochondrial Genetics and Function as Determinants of Bone Phenotype and Aging.Current osteoporosis reports · 2023Review
- Efferocytosis by bone marrow mesenchymal stromal cells disrupts osteoblastic differentiation via mitochondrial remodeling.Cell death & disease · 2023Article
- 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.International journal of molecular sciences · 2023Article
- Role of the Mitochondrial Permeability Transition in Bone Metabolism and Aging.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2023Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Cellular bioenergetics is a promising new therapeutic target in aging, cancer, and diabetes because these pathologies are characterized by a shift from oxidative to glycolytic metabolism. We have previously reported such glycolytic shift in aged bone as a major contributor to bone loss in mice. We and others also showed the importance of oxidative phosphorylation (OxPhos) for osteoblast differentiation. It is therefore reasonable to propose that stimulation of OxPhos will have bone anabolic effect. One strategy widely used in cancer research to stimulate OxPhos is inhibition of glycolysis. In this work, we aimed to evaluate the safety and efficacy of pharmacological inhibition of glycolysis to stimulate OxPhos and promote osteoblast bone-forming function and bone anabolism. We tested a range of glycolytic inhibitors including 2-deoxyglucose, dichloroacetate, 3-bromopyruvate, and oxamate. Of all the studied inhibitors, only a lactate dehydrogenase (LDH) inhibitor, oxamate, did not show any toxicity in either undifferentiated osteoprogenitors or osteoinduced cells in vitro. Oxamate stimulated both OxPhos and osteoblast differentiation in osteoprogenitors. In vivo, oxamate improved bone mineral density, cortical bone architecture, and bone biomechanical strength in both young and aged C57BL/6J male mice. Oxamate also increased bone formation by osteoblasts without affecting bone resorption. In sum, our work provided a proof of concept for the use of anti-glycolytic strategies in bone and identified a small molecule LDH inhibitor, oxamate, as a safe and efficient bone anabolic agent. © 2020 American Society for Bone and Mineral Research (ASBMR).
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.