Academic Journal
Activation of the proton-sensing GPCR, GPR65 on fibroblast-like synoviocytes contributes to inflammatory joint pain.
| العنوان: | Activation of the proton-sensing GPCR, GPR65 on fibroblast-like synoviocytes contributes to inflammatory joint pain. |
|---|---|
| المؤلفون: | Pattison, Luke A, Rickman, Rebecca H, Hilton, Helen, Dannawi, Maya, Wijesinghe, Susanne N, Ladds, Graham, Yang, Li V, Jones, Simon W, Smith, Ewan St John |
| بيانات النشر: | Proceedings of the National Academy of Sciences Department of Pharmacology //doi.org/10.1073/pnas.2410653121 Proc Natl Acad Sci U S A |
| سنة النشر: | 2024 |
| المجموعة: | Apollo - University of Cambridge Repository |
| مصطلحات موضوعية: | GPCR, acidosis, arthritis, inflammatory pain, nociception, Receptors, G-Protein-Coupled, Animals, Humans, Synoviocytes, Mice, Fibroblasts, Osteoarthritis, Arthralgia, Male, Inflammation, Protons, Signal Transduction, Synovial Fluid |
| الوصف: | 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. ; BBSRC Doctoral Training Programme (BB/MO11194/1) Corpus Christi College MRC (MR/W002426/1 & MR/W026961/1) AstraZeneca (G104108) BBSRC / GSK (BB/V509528/1) Wellcome Trust (225856/Z/22/Z) Versus Arthritis (21530) Royal Society (NF\R2\212001) From the paper: The authors acknowledge the following sources of funding to support this work: University of Cambridge BBSRC Doctoral Training Programme BB/MO11194/1 (LAP); Corpus Christi College, University of Cambridge Studentship (LAP); MRC Grant MR/W002426/1 (LAP, ESS); AstraZeneca PhD Studentship G104108 (RHR); BBSRC/GSK iCASE PhD Studentship BB/V509528/1 (HH); Wellcome Trust Grant 225856/Z/22/Z (MD, ESS); MRC Grant MR/W026961/1 (SNW, SWJ); Versus Arthritis Grant 21530 (SNW, SWJ); Royal Society Industry Fellowship NF\R2\212001 (GL). |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| Relation: | https://doi.org/10.17863/CAM.106374; https://www.repository.cam.ac.uk/handle/1810/376551.2 |
| الاتاحة: | https://www.repository.cam.ac.uk/handle/1810/376551.2 |
| Rights: | Attribution 4.0 International ; https://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.6989824A |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |