title: Ovarian cancer G-protein-coupled receptor 1 induces the expression of the pain mediator prostaglandin E2 in response to an acidic extracellular environment in human osteoblast-like cells.
abstract: Although bone pain in osteoporosis and skeletal metastasis is an expected consequence of fracture, there are other underlying causes responsible. Our study demonstrated that ovarian cancer G-protein-coupled receptor 1 detected extracellular protons in MG63 cells, and regulated osteoblast functions, such as prostaglandin E2 production, in response to acidic circumstances. In this work, we measured inositol phosphate production, intracellular Ca(2+) concentration, prostaglandin E2 production, and cyclic adenosine monophosphate accumulation in MG63 cells exposed to extracellular acidification. Extracellular acidity induced a transient increase in Ca(2+) concentration and inositol phosphate production. Acidification also induced prostaglandin E2 production, resulting in cyclic adenosine monophosphate accumulation. A small interfering RNA specific for the ovarian cancer G-protein-coupled receptor 1 markedly inhibited these proton-induced actions in MG63 cells. These results indicated that the involvement of ovarian cancer G-protein-coupled receptor 1 in acidic extracellular environment may be an underlying mechanism responsible for bone pain in osteoporosis or bone metastasis without clinically proved fractures.
authors: Department of Orthopaedics, The First Affiliated Hospital of China Medical University, Shenyang, China. wangd_juq@hotmail.com
authors: Juqiang
authors: J
authors: Wang
authors: Yu
authors: Y
authors: Sun
authors: Hideaki
authors: H
authors: Tomura
authors: Fumikazu
authors: F
authors: Okajima
mesh_terms: D000143:Acids / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D007295:Inositol Phosphates / Q000378:metabolism; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D010146:Pain / Q000378:metabolism*; D011522:Protons; D034741:RNA, Small Interfering / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000143:Acids; D016861:Cyclooxygenase Inhibitors; C486281:GPR68 protein, human; D007295:Inositol Phosphates; D011522:Protons; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled; D000242:Cyclic AMP; D015232:Dinoprostone