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Cyclooxygenase‐2 Expression and Prostaglandin E 2 Production in Response to Acidic pH Through OGR1 in a Human Osteoblastic Cell Line
Author(s) -
Tomura Hideaki,
Wang JuQiang,
Liu JinPeng,
Komachi Mayumi,
Damirin Alatangaole,
Mogi Chihiro,
Tobo Masayuki,
Nochi Hiromi,
Tamoto Koichi,
Im DoonSoon,
Sato Koichi,
Okajima Fumikazu
Publication year - 2008
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.080236
Subject(s) - extracellular , phospholipase c , intracellular , microbiology and biotechnology , inositol trisphosphate , cyclooxygenase , calcium in biology , phospholipase , cell culture , biology , calcium , biochemistry , inositol , endocrinology , prostaglandin e , gq alpha subunit , prostaglandin , signal transduction , medicine , receptor , g protein , enzyme , genetics
Acidosis has been shown to induce depletion of bone calcium from the body. This calcium release process is thought to be partially cell mediated. In an organ culture of bone, acidic pH has been shown to induce cyclooxygenase‐2 (COX‐2) induction and prostaglandin E 2 (PGE 2 ) production, resulting in stimulation of bone calcium release. However, the molecular mechanisms whereby osteoblasts sense acidic circumstances and thereby induce COX‐2 induction and PGE 2 production remain unknown. In this study, we used a human osteoblastic cell line (NHOst) to characterize cellular activities, including inositol phosphate production, intracellular Ca 2+ concentration ([Ca 2+ ] i ), PGE 2 production, and COX‐2 mRNA and protein expression, in response to extracellular acidification. Small interfering RNA (siRNA) specific to the OGR1 receptor and specific inhibitors for intracellular signaling pathways were used to characterize acidification‐induced cellular activities. We found that extracellular acidic pH induced a transient increase in [Ca 2+ ] i and inositol phosphate production in the cells. Acidification also induced COX‐2 induction, resulting in PGE 2 production. These proton‐induced actions were markedly inhibited by siRNA targeted for the OGR1 receptor and the inhibitors for G q/11 protein, phospholipase C, and protein kinase C. We conclude that the OGR1/G q/11 /phospholipase C/protein kinase C pathway regulates osteoblastic COX‐2 induction and subsequent PGE 2 production in response to acidic circumstances.