Effect of raloxifene and its interaction with human PTH on bone formation.
We studied the of effects raloxifene alone or in combination with human PTH (hPTH) 1-34 in mineralizing cultures of SaOS-2 cells. Raloxifene (10(-8)-10(-6) M) increased bone nodule formation in cultures of SaOS-2 cells when added intermittently from day 8 to day 17. A single 24-h treatment with 10(-8) M hPTH (1-34) at day 8 reduced the nodule area by 75.6% at day 17, and raloxifene added concomitantly with hPTH (1-34) reduced this inhibitory effect in a dose-dependent manner. Raloxifene also reduced the hPTH (1-34)-induced inhibition of alkaline phosphatase (ALP) activity. The 10-fold stimulation of c-fos mRNA expression by hPTH (1-34) was not influenced by raloxifene co-treatment. The protein kinase A (PKA) inhibitor 6-22 amide (1.7 nM) and the protein kinase C (PKC) inhibitor-bisindolylmaleimide 1 (10 nM) did not influence the separate effects of PTH and raloxifene on mineralized bone nodule formation. This is the first report on the interaction of PTH and raloxifene in an osteoblast culture system.
Calcium Research Lab, St. Michael Hospital, Toronto, Ontario, Canada.
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Y
Lin
L J F
LJ
Liu
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T
Murray
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Sodek
L
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Rao
D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects* / Q000502:physiology; D010281:Parathyroid Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D020845:Selective Estrogen Receptor Modulators; D020849:Raloxifene Hydrochloride; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D000469:Alkaline Phosphatase; C070515:bisindolylmaleimide I