title: Protein Kinase C is a mediator of the synthesis and secretion of osteoprotegerin in osteoblast-like cells.
abstract: Osteoprotegerin (OPG) is a member of the TNF receptor superfamily and plays a critical role in the development of osteoclasts from precursor cells. OPG is produced by a variety of cells of mesenchymal origin and has been demonstrated to be present in osteoblasts and osteocytes. However, the mechanisms of regulation of OPG production and secretion are not known. Using a highly specific polyclonal antibody, we demonstrate that OPG is synthesized and secreted by osteoblast-like cells in culture. We further show that phorbol myristate acetate, an activator of protein kinase C, activated the secretion of OPG. Further, the increased secretion of OPG correlated well with a corresponding increase in OPG mRNA abundance. In addition, OPG promoter stably integrated into an osteoblast cell line was activated by phorbol myristate acetate. The increase in OPG expression was blocked by an inhibitor of protein kinase C, although the basal OPG expression was not altered. These results suggest that activation of the protein kinase C pathway may play a critical role in OPG expression.
authors.affiliation: Gene Regulation, Bone and Inflammation Research Division, DC 0403, Lilly Research Labs, Indianapolis, IN 46285, USA.
authors.forename: Xuhao
authors.initials: X
authors.lastname: Yang
authors.forename: David
authors.initials: D
authors.lastname: Halladay
authors.forename: Jude E
authors.initials: JE
authors.lastname: Onyia
authors.forename: T John
authors.initials: TJ
authors.lastname: Martin
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Chandrasekhar
mesh_terms: D000818:Animals; D000906:Antibodies / Q000737:chemistry; D015152:Blotting, Northern; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006023:Glycoproteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D010006:Osteoblasts / Q000378:metabolism*; D053244:Osteoprotegerin; D011401:Promoter Regions, Genetic; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis* / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000737:chemistry / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D000906:Antibodies; D004791:Enzyme Inhibitors; D006023:Glycoproteins; D007211:Indoles; D008301:Maleimides; D053244:Osteoprotegerin; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; C506030:TNFRSF11B protein, human; C506032:Tnfrsf11b protein, rat; D011493:Protein Kinase C; C070515:bisindolylmaleimide I; D013755:Tetradecanoylphorbol Acetate