Effect of parathyroid hormone on arachidonic acid metabolism in mouse osteoblasts: permissive action of dexamethasone.
We examined the regulation of arachidonic acid (AA) metabolism in primary cultures of mouse osteoblasts under steady state and after acute stimulation by PTH. Both dexamethasone-treated and untreated cells were evaluated, as glucocorticoids are known to modulate some actions of PTH in osteoblasts and to affect arachidonic acid metabolism in cells in general. Cells were labeled with [3H]AA for 3 h, followed by a 20-h equilibrium period, then exposed to 10(-8) M PTH for different time periods ranging from 2-60 min. The results showed that although osteoblasts maintained in vitro in the absence of dexamethasone were responsive to PTH, as measured by cAMP production (50-fold increase), PTH had no effect on the distribution of AA in phospholipids and did not induce the release of free AA from phospholipid pools. After 7-day treatment of the cells with 4 x 10(-7) M dexamethasone, 15-min PTH stimulation resulted in a significant increase in free AA within the cells (mean +/- SE, +142 +/- 11%; n = 9) and a short-lived change in the distribution of AA within cellular phospholipids (phosphatidylethanolamine, -63 +/- 3%; phosphatidylinositol, +168 +/- 7%; phosphatidylserine, +296 +/- 50%; sphingomyelin, +220 +/- 20%; lysophosphatidylcholine, +634 +/- 31%; mean +/- SE; n = 3), despite the fact that no changes in PTH-induced cAMP production were observed. Because the release of free AA is an essential step in the production of eicosanoid metabolites that could act as second messengers, these findings suggest that corticosteroid treatment may activate signal transduction pathways for PTH which are latent in untreated cells, and thereby explain at least in part the profound effects of corticosteroids on osteoblast function.
Suarez
F
F
CNRS UA 583, Hôpital Necker Enfants Malades, Paris, France.
Silve
C
C
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001095:Arachidonic Acids / Q000378:metabolism*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007700:Kinetics; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D010741:Phospholipases A / Q000494:pharmacology; D010743:Phospholipids / Q000378:metabolism; D019379:Teriparatide
D001095:Arachidonic Acids; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D010743:Phospholipids; D019379:Teriparatide; D003907:Dexamethasone; D000242:Cyclic AMP; D010741:Phospholipases A