Specific induction of heat shock protein 27 by glucocorticoid in osteoblasts

Abstract

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.

Low-Intensity Pulsed Ultrasound Stimulation Enhances Heat-Shock Protein 90 and Mineralized Nodule Formation in Mouse Calvaria-Derived Osteoblasts

“…4). Other studies have demonstrated that p38 MAP-kinase-dependent osteoblast differentiation is important, 46,51,52 even though OSX mRNA expression was only suppressed by LIPUS stimulation at 24 h in our study. However, the strongest mineral accumulation was apparent in LIPUS-treated osteoblasts.…”

Anthrax lethal factor represses glucocorticoid and progesterone receptor activity

“…Previous findings have shown that stimuli-induced activation, not basal repression͞inhibition, of the MEK pathways can repress GR (45)(46)(47)(48)(49)(50)(51)(52). However, one study has shown that SB203580 prevents Dex-induced Hsp27 production in osteoclasts (53), suggesting that the relationship between LeTx repression of GR and p38 requires further investigation.…”

Glucocorticoid induces apoptosis of osteoblast cells through the activation of glycogen synthase kinase 3β

“…Previous reports showed that p38-MAPK is involved in apoptosis [14,23] and activated during the GC-induced apoptosis [15,19]. Recent studies demonstrated that p38-MAPK plays many critical roles in apoptosis and survival in osteoblasts [16,17].…”

“…The p38-MAPK activation is essential for differentiation of osteoblasts [13]. However, p38-MAPK phosphorylation in osteosarcoma and osteoblasts cells is related to apoptosis through the subsequent activation of caspase-3 [14,15]. The p38-MAPK has been shown to play many important roles in apoptosis and survival in osteoblasts [16,17].…”