Parathyroid hormone increases mac25/insulin-like growth factor-binding protein-related protein-1 expression in cultured osteoblasts.
PTH induces the synthesis of insulin-like growth factor I (IGF-I) and regulates the expression of IGF-binding proteins (IGFBP) in osteoblast cultures. IGFBP-related protein-1 (IGFBP-RP-1), the product of the mac25 gene, binds IGF-I, IGF-II, and insulin. We tested the actions of PTH on the expression of mac25/IGFBP-RP-1 in cultures of osteoblast-enriched cells from 22-day-old fetal rat calvariae (Ob cells). PTH at 0.1-10 nM for 6-48 h increased mac25/IGFBP-RP-1 messenger RNA (mRNA) levels in Ob cells, an effect not altered by cycloheximide. PGE2 increased mac25/IGFBP-RP-1 mRNA levels, but indomethacin did not modify basal or PTH-stimulated mac25/IGFBP-RP-1 expression. The decay of mac25/IGFBP-RP-1 mRNA in transcriptionally arrested Ob cells was not modified by PTH, and PTH increased the rate of IGFBP-RP-1 transcription. GH, insulin, bone morphogenetic protein-2, fibroblast growth factor-2, platelet-derived growth factor BB, IGF-I, and IGF-II did not modify mac25/IGFBP-RP-1 expression, whereas transforming growth factor-beta1 was modestly stimulatory. In conclusion, PTH stimulates mac25/IGFBP-RP-1 transcription in osteoblasts, an effect that could be relevant to the actions of PTH in bone.
Pereira
R C
RC
Department of Research, Saint Francis Hospital and Medical Center, Hartford, Connecticut 06105-1299, USA.
Canalis
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E
D000818:Animals; D015152:Blotting, Northern; D001842:Bone and Bones / Q000196:embryology; D002352:Carrier Proteins / Q000235:genetics*; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D007213:Indomethacin / Q000494:pharmacology; D018969:Insulin-Like Growth Factor Binding Proteins; D007700:Kinetics; D010006:Osteoblasts / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D002352:Carrier Proteins; D016861:Cyclooxygenase Inhibitors; D018969:Insulin-Like Growth Factor Binding Proteins; D010281:Parathyroid Hormone; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; C102529:insulin-like growth factor binding protein-related protein 1; D003513:Cycloheximide; D015232:Dinoprostone; D007213:Indomethacin