ArticleAnnals of the rheumatic diseases2024
Acod1-mediated inhibition of aerobic glycolysis suppresses osteoclast differentiation and attenuates bone erosion in arthritis.
Article in Annals of the rheumatic diseases, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed.
- Glucose metabolism in osteoporosis: A potential therapeutic target (Review).International journal of molecular medicine · 2026Review
- Glycolysis in bone remodeling: from energy supply to signaling regulation.Molecular biology reports · 2026Review
- OXR1 is a dual redox-mitochondrial checkpoint governing osteoclast differentiation and bone loss in an osteoporosis mouse model.Nature communications · 2026Article
- Itaconate and its derivatives in human health and diseases.Signal transduction and targeted therapy · 2026Review
- Neuroimmune Regulation in Posttraumatic Bone Repair: From Inflammatory Transition to Neurovascular Coupling and Functional Recovery.Journal of cellular physiology · 2026Review
- Review
- Bletilla striata polysaccharide inhibits osteoclast differentiation by suppressing macrophage glycolysis and MMP9 expression.In vitro cellular & developmental biology. Animal · 2026Article
- Tri-modal nanocatalytic microenvironment regulations for macrophage reprogramming and osteoporotic fracture healing promotion.Materials today. Bio · 2026Article
- The IRE1-XBP1s Axis Drives Inflammatory Osteolysis by Regulating a 5-HT Dependent Endogenous Anti-Autophagy Mechanism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Review
- Lactate programs CRIP1 protein lactylation to drive synovial proliferation in rheumatoid arthritis.JCI insight · 2026Article
- The alkylation of AIM2 by itaconate mediates macrophage PANoptosis during sepsis.Cellular & molecular immunology · 2026Article
- Automated quantitative analysis of osteoclast numbers and areas in cell culture plates using the YOLOv8 instance segmentation model.MethodsX · 2026Article
- ACOD1 deficiency promotes DDX1 methylation-mediated mitochondrial dysfunction and dermal papilla cell senescence in androgenetic alopecia.BMC medicine · 2026Article
- Regulating Glucose Metabolism Enzymes for Osteoporosis Therapy: Current and Future Approaches.International journal of molecular sciences · 2026Review
- M-CSF priming enhances the efficiency and reproducibility of hiPSC-derived osteoclast differentiation and pharmacological responsiveness to anti-resorptive agents.Scientific reports · 2026Article
- ACOD1-itaconate in macrophage attenuates oxidative stress and inflammation in benign airway stenosis by upregulating and transferring FTH1.Redox biology · 2026Article
- Beyond M1/M2: The Pivotal Role of Macrophage Metabolic Reprogramming in Chronic Bone Disease and Targeted Intervention.International journal of molecular sciences · 2026Review
- STAT1 itaconation prevents macrophage cytolistic mtDNA -induced inflammation in wear particle-induced aseptic loosening.Cell communication and signaling : CCS · 2026Article
- Emodin Attenuates Rheumatoid Arthritis by Modulating the NF-κB/HIF-1α/VEGF Signaling Pathway.International journal of molecular sciences · 2026Article
Corrections and comments
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Authors and funding
16 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesMetabolic changes are crucially involved in osteoclast development and may contribute to bone degradation in rheumatoid arthritis (RA). The enzyme aconitate decarboxylase 1 (Acod1) is known to link the cellular function of monocyte-derived macrophages to their metabolic status. As osteoclasts derive from the monocyte lineage, we hypothesised a role for Acod1 and its metabolite itaconate in osteoclast differentiation and arthritis-associated bone loss.
methodsItaconate levels were measured in human peripheral blood mononuclear cells (PBMCs) of patients with RA and healthy controls by mass spectrometry. Human and murine osteoclasts were treated with the itaconate derivative 4-octyl-itaconate (4-OI) in vitro. We examined the impact of Acod1-deficiency and 4-OI treatment on bone erosion in mice using K/BxN serum-induced arthritis and human TNF transgenic (hTNFtg) mice. SCENITH and extracellular flux analyses were used to evaluate the metabolic activity of osteoclasts and osteoclast progenitors. Acod1-dependent and itaconate-dependent changes in the osteoclast transcriptome were identified by RNA sequencing. CRISPR/Cas9 gene editing was used to investigate the role of hypoxia-inducible factor (Hif)-1α in Acod1-mediated regulation of osteoclast development.
resultsItaconate levels in PBMCs from patients with RA were inversely correlated with disease activity. Acod1-deficient mice exhibited increased osteoclast numbers and bone erosion in experimental arthritis while 4-OI treatment alleviated inflammatory bone loss in vivo and inhibited human and murine osteoclast differentiation in vitro. Mechanistically, Acod1 suppressed osteoclast differentiation by inhibiting succinate dehydrogenase-dependent production of reactive oxygen species and Hif1α-mediated induction of aerobic glycolysis.
conclusionAcod1 and itaconate are crucial regulators of osteoclast differentiation and bone loss in inflammatory arthritis.
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