Parathyroid hormone induces prostaglandin G/H synthase-2 expression by a cyclic adenosine 3',5'-monophosphate-mediated pathway in the murine osteoblastic cell line MC3T3-E1.
Prostaglandin G/H synthase (PGHS), a central enzyme for PG synthesis, is encoded by the constitutively expressed PGHS-1 and the inducible PGHS-2. The goal of this project was to study the regulation of PGHS-2 gene expression by PTH and its possible signaling pathways in osteoblastic MC3T3-E1 cultures. Bovine PTH-(1-34) at 0.01-10 nM increased PGHS-2, but not PGHS-1, messenger RNA (mRNA) levels. The effect of PTH was maximal at 1 h and decreased almost to control levels by 6 h. Phorbol myristate acetate (PMA), forskolin, and 8-bromo-cAMP increased PGHS-2 mRNA levels, whereas ionomycin had no effect. PTH, forskolin, and PMA increased the release of PGE2 into the culture medium. Pretreatment of cells with 0.1 microM PMA for 16 h blocked the induction of PGHS-2 mRNA levels by PMA, but did not alter the effects of PTH and forskolin. However, treatment of cells with 30 microM H-89, a protein kinase A inhibitor, significantly reduced the ability of PTH and forskolin to induce PGHS-2 mRNA levels. Moreover, PTH-(3-34) at 0.1-100 nM did not induce PGHS-2 mRNA levels. Our results show that PTH can rapidly and transiently induce PGHS-2 mRNA levels in osteoblastic MC3T3-E1 cells, primarily via the cAMP-protein kinase A signal transduction pathway. Induction of PGHS-2 may play a key role in mediating some actions of PTH on bone metabolism and gene expression.
Tetradis
S
S
Department of Oral Diagnosis, School of Dental Medicine, University of Connecticut Health Center, Farmington 06030, USA.
Pilbeam
C C
CC
Liu
Y
Y
Kream
B E
BE
D000818:Animals; D002417:Cattle; D002460:Cell Line; D000242:Cyclic AMP / Q000502:physiology*; D051379:Mice; D010006:Osteoblasts / Q000201:enzymology*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D011493:Protein Kinase C / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction
D010281:Parathyroid Hormone; D012333:RNA, Messenger; D000242:Cyclic AMP; D011451:Prostaglandin-Endoperoxide Synthases; D011493:Protein Kinase C