ArticleProceedings of the National Academy of Sciences of the United States of America2024
Activation of the proton-sensing GPCR, GPR65 on fibroblast-like synoviocytes contributes to inflammatory joint pain.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Single-Cell and Mendelian Randomization Analyses Identify Macrophage Polarization and Efferocytosis Biomarkers in Osteoarthritis and Reveal Their Regulatory Mechanisms.Iranian journal of biotechnology · 2026Article
- Joint Acidosis and GPR68 Signaling in Osteoarthritis: Implications for Cartilage Gene Regulation.Genes · 2026Review
- pH sensing and inflammation: linking acidic microenvironments to immune reprogramming.Frontiers in immunology · 2026Review
- Neuropeptide Y signaling in osteoarthritis pain: neuroimmune mechanisms, joint remodeling, and translational opportunities.Frontiers in pain research (Lausanne, Switzerland) · 2026Review
- Mechanisms of pain occurrence in osteoarthritis: peripheral triggers, sensitization, and the path to persistence.Frontiers in immunology · 2026Review
- Not Just Neurons: Pain Is Orchestrated in Partnership with Many Non-neuronal Cells.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Review
- Artemin sensitises mouse (Mus musculus) and naked mole-rat (Heterocephalus glaber) sensory neurons in vitro.Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology · 2025Article
- Joint Acidosis and Acid-Sensing Receptors and Ion Channels in Osteoarthritis Pathobiology and Therapy.Cells · 2025Review
- Whole body and hematopoietic cell-specific deletion of G-protein coupled receptor 65 (GPR65) improves insulin sensitivity in diet-induced obese mice.Molecular metabolism · 2025Article
- Activation of the proton-sensing GPCR, GPR65 on fibroblast-like synoviocytes contributes to inflammatory joint pain.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
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9 authors.
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Abstract
Inflammation is associated with localized acidosis, however, attributing physiological and pathological roles to proton-sensitive receptors is challenging due to their diversity and widespread expression. Here, agonists of the proton-sensing GPCR, GPR65, were systematically characterized. The synthetic agonist BTB09089 (BTB) recapitulated many proton-induced signaling events and demonstrated selectivity for GPR65. BTB was used to show that GPR65 activation on fibroblast-like synoviocytes (FLS), cells that line synovial joints, results in the secretion of proinflammatory mediators capable of recruiting immune cells and sensitizing sensory neurons. Intra-articular injection of BTB resulted in GPR65-dependent sensitization of knee-innervating neurons and nocifensive behaviors in mice. Stimulation of GPR65 on human FLS also triggered the release of inflammatory mediators and synovial fluid samples from human osteoarthritis patients were shown to activate GPR65. These results suggest a role of GPR65 in mediating cell-cell interactions that drive inflammatory joint pain in both mice and humans.
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