ArticleJCI insight2019
Inhibition of 4-aminobutyrate aminotransferase protects against injury-induced osteoarthritis in mice.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 42 citations in OpenAlex.
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- Targeting the mitochondrial metabolite-dynamics-MDVs-MitoEVs axis: a new frontier in osteoarthritis management.Journal of translational medicine · 2026Review
- Metabolite-neuro-immune relay in chronic pain: spatial-temporal lactate, succinate and itaconate signalling as drivers of glial reprogramming and neuronal sensitisation.Frontiers in pharmacology · 2026Review
- New therapeutic target for osteoarthritis: modulating immune-metabolic aberrations and micromilieu remodeling in underlying bone.Frontiers in pharmacology · 2026Review
- Emerging roles of the metabolite succinate in bone-related diseases.Journal of Zhejiang University. Science. B · 2025Review
- Altered Inhibitory Synaptic Transmission and Changes in GABAergic Markers in the Hippocampus of Genetic and Environmental Animal Model of Autism.Neurochemical research · 2025Article
- NFIA regulates articular chondrocyte fatty acid metabolism and joint homeostasis.Science translational medicine · 2025Article
- Diagnostic and prognostic potential of biomarkers in femoroacetabular impingement syndrome: A systematic review.Journal of experimental orthopaedics · 2025Review
- Current cutting-edge omics techniques on musculoskeletal tissues and diseases.Bone research · 2025Review
- Metabolic Reprogramming in Stromal and Immune Cells in Rheumatoid Arthritis and Osteoarthritis: Therapeutic Possibilities.European journal of immunology · 2025Review
- Tissue-specific roles of de novo DNA methyltransferases.Epigenetics & chromatin · 2025Review
- Anti-gamma-aminobutyric acid B receptor antibody-associated limbic encephalitis in relapsing polychondritis: a rare case report and literature review.Frontiers in immunology · 2025Review
- Primary cartilage transcriptional signatures reflect cell-type-specific molecular pathways underpinning osteoarthritis.American journal of human genetics · 2024Article
- Shank3 Deficiency Results in a Reduction in GABAergic Postsynaptic Puncta in the Olfactory Brain Areas.Neurochemical research · 2024Article
- Gut-joint axis: Oral Probiotic ameliorates Osteoarthritis.Journal of traditional and complementary medicine · 2024Article
- DNA methylation-mediated Rbpjk suppression protects against fracture nonunion caused by systemic inflammation.The Journal of clinical investigation · 2023Article
- DNA methylation-mediated Rbpjk suppression protects against fracture nonunion caused by systemic inflammation.The Journal of clinical investigation · 2023Article
- Epigenetic dysregulation of articular cartilage during progression of hip femoroacetabular impingement disease.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2023Article
- Cross-talk of inflammation and chondrocyte intracellular metabolism in osteoarthritis.Osteoarthritis and cartilage · 2023Review
- Recent Advances in Small Molecule Inhibitors for the Treatment of Osteoarthritis.Journal of clinical medicine · 2023Review
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Recently we demonstrated that ablation of the DNA methyltransferase enzyme, Dnmt3b, resulted in catabolism and progression of osteoarthritis (OA) in murine articular cartilage through a mechanism involving increased mitochondrial respiration. In this study, we identify 4-aminobutyrate aminotransferase (Abat) as a downstream target of Dnmt3b. Abat is an enzyme that metabolizes γ-aminobutyric acid to succinate, a key intermediate in the tricarboxylic acid cycle. We show that Dnmt3b binds to the Abat promoter, increases methylation of a conserved CpG sequence just upstream of the transcriptional start site, and inhibits Abat expression. Dnmt3b deletion in articular chondrocytes results in reduced methylation of the CpG sequence in the Abat promoter, which subsequently increases expression of Abat. Increased Abat expression in chondrocytes leads to enhanced mitochondrial respiration and elevated expression of catabolic genes. Overexpression of Abat in murine knee joints via lentiviral injection results in accelerated cartilage degradation following surgical induction of OA. In contrast, lentiviral-based knockdown of Abat attenuates the expression of IL-1β-induced catabolic genes in primary murine articular chondrocytes in vitro and also protects against murine articular cartilage degradation in vivo. Strikingly, treatment with the FDA-approved small-molecule Abat inhibitor, vigabatrin, significantly prevents the development of injury-induced OA in mice. In summary, these studies establish Abat as an important new target for therapies to prevent OA.
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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.