title: Low-dose parathyroid hormone and estrogen reverse alkaline phosphatase activity suppressed by dexamethasone in mouse osteoblastic cells.
abstract: Glucocorticoid (GC)-induced osteoporosis (GIO) is frequently seen in patients with excessive GC. Numerous questions remain to be clarified about the pathogenesis and treatment of GIO, and the mechanism of GC-inhibited bone formation is not well known. Several studies suggest that parathyroid hormone (PTH) and hormone replacement therapy are effective for GIO. We therefore investigated whether PTH and estrogen would affect cell proliferation and alkaline phosphatase (ALP) activity inhibited by dexamethasone (Dex) in mouse osteoblastic cell-line MC3T3-E1 cells. Low-dose (10(-11) M) PTH as well as 10(-8) M 17-beta-estradiol (17beta-E2) significantly attenuated Dex-inhibited ALP activity, although 10(-8) M PTH did not affect it. ICI 182780 (10(-8) M) antagonized the effects of 17beta-E(2) on Dex-suppressed ALP activity. Neutralizing anti-IGF-I antibody (3 microg/ml) blocked the reverse effects of 17beta-E2 on ALP activity suppressed by Dex. PTH (10(-11) M), but not 17beta-E2, significantly attenuated [3H]thymidine incorporation inhibited by Dex. On the other hand, PTH and estrogen did not affect the level of 11-beta-hydrosteroid dehydrogenase type I mRNA increased by Dex. In conclusion, the present study demonstrated that low-dose PTH and estrogen reversed Dex-inhibited ALP activity in the mouse osteoblastic cell-line.
authors.affiliation: Division of Endocrinology/Metabolism, Neurology and Hematology/Oncology, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors.forename: Mei-Fway
authors.initials: MF
authors.lastname: Iu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kaji
authors.forename: Junko
authors.initials: J
authors.lastname: Naito
authors.forename: Hideaki
authors.initials: H
authors.lastname: Sowa
authors.forename: Toshitsugu
authors.initials: T
authors.lastname: Sugimoto
authors.forename: Kazuo
authors.initials: K
authors.lastname: Chihara
mesh_terms: D042842:11-beta-Hydroxysteroid Dehydrogenases / Q000096:biosynthesis; D000469:Alkaline Phosphatase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D016723:Bone Remodeling / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects* / Q000201:enzymology; D010281:Parathyroid Hormone / Q000008:administration & dosage*
chemical_list: D010281:Parathyroid Hormone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D003907:Dexamethasone; D042842:11-beta-Hydroxysteroid Dehydrogenases; D000469:Alkaline Phosphatase