enhancement by hsp90 inhibitor of pgd2stimulated hsp27 induction in osteoblasts suppression of sapkjnk and p38 map kinase heat shock protein hsp 90 that is ubiquitously expressed in various tissues is a major molecular chaperone we have previously demonstrated that prostaglandin d2 pgd2 a bone remodeling factor elicits the expression of hsp27 a small hsp through stressactivated protein kinasecjun nterminal kinase sapkjnk and p38 mitogenactivated protein map kinase in osteoblastlike mc3t3e1 cells in the present study we investigated the involvement of hsp90 in the pgd2stimulated hsp27 induction and the underlying mechanism in mc3t3e1 cells onalespib an inhibitor of hsp90 significantly enhanced the pgd2stimulated hsp27 induction in addition geldanamycin another hsp90 inhibitor potentiated the hsp27 induction both onalespib and geldanamycin markedly amplified the pgd2induced phosphorylation of sapkjnk and p38 map kinase sp600125 an inhibitor of sapkjnk and sb203580 an inhibitor of p38 map kinase suppressed the amplification by onalespib of the pgd2stimulated hsp27 induction these results strongly suggest that hsp90 plays a negative role in the hsp27 induction stimulated by pgd2 in osteoblasts and that the inhibitory effect of hsp90 is mediated through the regulation of sapkjnk and p38 map kinase