Activation of the proton-sensing GPCR, GPR65 on fibroblast-like synoviocytes contributes to inflammatory joint pain.

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. Stimula

SUBMITTER: Pattison LA 

PROVIDER: S-EPMC11665855 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature