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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.
The international journal of biochemistry & cell biology 07/2012; 44(11):1937-41. · 4.89 Impact Factor