Glucocorticoid regulation of calcitonin receptor in mouse osteoclast-like multinucleated cells.
Abundant multinucleated cells (MNCs) are formed in cocultures of mouse osteoblastic cells and marrow cells in the presence of 1 alpha, 25-dihydroxyvitamin D3 [1 alpha, 25(OH)2D3], and these cells have the properties of osteoclasts (OCs). In this study using the mammalian OCs, we tried to clarify the role of glucocorticoids (GCs) in calcitonin receptors (CTR) and CT-responsive cAMP production in OCs. Dexamethasone (DEX) dose and time dependently enhanced the specific binding of [125I]salmon calcitonin (sCT). When the MNCs were preincubated with DEX for 24 h, the effect was evident at 10(-9) M and the maximum effect was obtained at 10(-7) M. The effect developed over 12-48 h at doses of 10(-9) and 10(-6) M DEX. The numbers of CTR-positive mononuclear cells and MNCs were not altered by the DEX treatment. Prednisolone and triamcinolone reproduced the DEX effect, but 17 beta-estradiol, progesterone, testosterone, aldosterone, and 1 alpha, 25(OH)2D3 did not. RU486, a GC receptor antagonist, attenuated the effect of DEX to enhance the specific binding of [125I]sCT. From a Scatchard plot analysis, DEX enhanced CTR number (212 +/- 64%) with a minimal change in the affinity to sCT. Autoradiographic studies using [125I]sCT showed that DEX enhanced the density of the grains on the tartrate-resistant acid phosphatase (TRAP)-positive MNCs and mononuclear cells, but not on other types of cells. DEX preincubation also enhanced sCT-stimulated but not prostaglandin E2- or forskolin-stimulated cAMP production.(ABSTRACT TRUNCATED AT 250 WORDS)
Wada
S
S
Third Department of Internal Medicine, National Defense Medical College, Saitama, Japan.
Akatsu
T
T
Tamura
T
T
Takahashi
N
N
Suda
T
T
Nagata
N
N
D000818:Animals; D000831:Animals, Newborn; D001345:Autoradiography; D001667:Binding, Competitive / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D002116:Calcitonin / Q000378:metabolism; D002117:Calcitriol / Q000494:pharmacology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis; D003513:Cycloheximide / Q000633:toxicity; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D015726:Giant Cells / Q000187:drug effects* / Q000378:metabolism; D005938:Glucocorticoids / Q000494:pharmacology*; D008297:Male; D051379:Mice; D015735:Mifepristone / Q000494:pharmacology; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism; D011239:Prednisolone / Q000494:pharmacology; D018003:Receptors, Calcitonin / Q000187:drug effects* / Q000378:metabolism; D014221:Triamcinolone / Q000494:pharmacology; D015854:Up-Regulation
D005938:Glucocorticoids; D018003:Receptors, Calcitonin; D014221:Triamcinolone; D015735:Mifepristone; D003907:Dexamethasone; C028815:salmon calcitonin; D002116:Calcitonin; D003513:Cycloheximide; D011239:Prednisolone; D000242:Cyclic AMP; D002117:Calcitriol