ArticleExperimental & molecular medicine2022
BCAT1 promotes osteoclast maturation by regulating branched-chain amino acid metabolism.
Article in Experimental & molecular medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- The Gut-Bone Axis and Skeletal Health: Regulatory Mechanisms and Therapeutic Applications of Plant-Derived Bioactive Compounds.Biomolecules · 2026Pooled it
- Article
- Copper homeostasis and cuproptosis: molecular mechanisms and therapeutic opportunities.Molecular biomedicine · 2026Review
- Targeting the PARP10-BCAT2 axis disrupts branched-chain amino-acid metabolism to suppress bone metastasis in lung cancer.Cell death & disease · 2026Article
- Branched‑chain amino acid metabolism and bone metabolism: Implications for osteoporosis pathogenesis and therapeutic strategies (Review).International journal of molecular medicine · 2026Review
- Polycaprolactone scaffolds promote a regeneration-supportive metabolic response attenuated in diabetes.Regenerative biomaterials · 2026Article
- Cu-doped dendritic biodegradable nanoplatforms for augmenting cuproptosis and tumor-starvation therapy through mitochondrial metabolic cascade modulation.Materials today. Bio · 2025Article
- Branched-Chain Amino Acids in Parkinson's Disease: Molecular Mechanisms and Therapeutic Potential.International journal of molecular sciences · 2025Review
- Proline-driven metabolic reprogramming promotes skeletal muscle hypertrophy and oxidative myofiber specification in porcine offspring: a stage-optimized maternal nutritional intervention.Journal of animal science and biotechnology · 2025Article
- Canagliflozin-Induced Adaptive Metabolism in Bone.Diabetes · 2025Article
- Essential role of the metabolite α-ketoglutarate in bone tissue and bone-related diseases.Acta biochimica et biophysica Sinica · 2025Review
- Divergent Requirements for Glutathione Biosynthesis During Osteoclast Differentiation In Vitro and In Vivo.Antioxidants (Basel, Switzerland) · 2025Article
- Glutaminolysis provides nucleotides and amino acids to regulate osteoclast differentiation in mice.EMBO reports · 2024Article
- Krüppel-like factors family in health and disease.MedComm · 2024Review
- The Role of Branched Chain Ketoacid Dehydrogenase Kinase (BCKDK) in Skeletal Muscle Biology and Pathogenesis.International journal of molecular sciences · 2024Article
- Metabolic regulation of skeletal cell fate and function.Nature reviews. Endocrinology · 2024Review
- Tricarboxylic Acid Cycle Regulation of Metabolic Program, Redox System, and Epigenetic Remodeling for Bone Health and Disease.Antioxidants (Basel, Switzerland) · 2024Review
- Anti‑osteoclastogenic effect of fermented mealworm extract by inhibiting RANKL‑induced NFATc1 action.Experimental and therapeutic medicine · 2024Article
- Unraveling the intricacies of osteoclast differentiation and maturation: insight into novel therapeutic strategies for bone-destructive diseases.Experimental & molecular medicine · 2024Review
- miR-21-5p Enriched Exosomes from Human Embryonic Stem Cells Promote Osteogenesis via YAP1 Modulation.International journal of nanomedicine · 2024Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Branched-chain aminotransferase 1 (BCAT1) transfers the amine group on branched-chain amino acids (BCAAs) to alpha-ketoglutarate. This generates glutamate along with alpha-keto acids that are eventually oxidized to provide the cell with energy. BCAT1 thus plays a critical role in sustaining BCAA concentrations and availability as an energy source. Osteoclasts have high metabolic needs during differentiation. When we assessed the levels of amino acids in bone marrow macrophages (BMMs) that were undergoing receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclast differentiation, we found that the BCAA levels steadily increase during this process. In vitro analyses then showed that all three BCAAs but especially valine were needed for osteoclast maturation. Moreover, selective inhibition of BCAT1 with gabapentin significantly reduced osteoclast maturation. Expression of enzymatically dead BCAT1 also abrogated osteoclast maturation. Importantly, gabapentin inhibited lipopolysaccharide (LPS)-induced bone loss of calvaria in mice. These findings suggest that BCAT1 could serve as a therapeutic target that dampens osteoclast formation.
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