Specific induction of heat shock protein 27 by glucocorticoid in osteoblasts.
It is generally recognized that osteoporosis is a common complication of patients with glucocorticoid excess and that glucocorticoid receptor is associated with heat shock protein (HSP) 70 and HSP90 in a heterocomplex. In the present study, we investigated whether glucocorticoid induces HSP27, HSP70, and HSP90 in osteoblast-like MC3T3-E1 cells. Dexamethasone time-dependently increased the levels of HSP27, while having no effect on the levels of HSP70 or HSP90. The effect of dexamethasone was dose-dependent in the range between 0.1 nM and 0.1 microM. Dexamethasone induced an increase of the levels of mRNA for HSP27. Dexamethasone induced the phosphorylation of p38 mitogen-activated protein (MAP) kinase. SB203580 and PD169316, inhibitors of p38 MAP kinase, suppressed the HSP27 accumulation by dexamethasone. In addition, SB203580 reduced the dexamethasone-stimulated increase of the mRNA levels for HSP27. The dexamethasone-induced phosphorylation of p38 MAP kinase was reduced by SB203580. These results strongly suggest that glucocorticoid stimulates the induction of neither HSP70 nor HSP90, but HSP27 in osteoblasts, and that p38 MAP kinase is involved in the induction of HSP27.
Department of Pharmacology, Gifu University School of Medicine, Japan. okozawa@cc.gifu-u.ac.jp
Osamu
O
Kozawa
Masayuki
M
Niwa
Daijiro
D
Hatakeyama
Haruhiko
H
Tokuda
Yutaka
Y
Oiso
Hiroyuki
H
Matsuno
Kanefusa
K
Kato
Toshihiko
T
Uematsu
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D018840:HSP70 Heat-Shock Proteins / Q000032:analysis; D018841:HSP90 Heat-Shock Proteins / Q000032:analysis; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D007093:Imidazoles / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D007093:Imidazoles; D011725:Pyridines; D012333:RNA, Messenger; D003907:Dexamethasone; D020928:Mitogen-Activated Protein Kinases; C408604:2-(4-nitrophenyl)-4-(4-fluorophenyl)-5-(4-pyridinyl)-1H-imidazole; C093642:SB 203580