Abstract
As for the pathogenesis of rheumatoid arthritis (RA), prostaglandins (PGs) act as
important mediators of inflammation and joint destruction. Among them, is well recognized as a potent regulator of osteoblastic functions. We previously
showed that stimulates the induction of heat shock protein 27 (HSP27) via protein kinase C (PKC)-dependent
p38 mitogen-activated protein (MAP) kinase and p44/p42 MAP kinase in osteoblast-like
MC3T3-E1 cells. Therefore, it is a current topic to clarify how HSP27 plays a role
for regulating osteoblastic functions in the lesion of RA. On the other hand, methotrexate
(MTX) is one of the most effective medicines for the treatment of RA. Here, we examined
the effect of MTX on -stimulated HSP27 induction in MC3T3-E1 cells. The cells were pretreated with various
doses of MTX including therapeutic dosage for RA, and then stimulated by . MTX significantly enhanced the - increased levels of HSP27 in a dose-dependent manner, although MTX alone had no
effect on the levels of HSP27. In addition, MTX amplified the -increased levels of HSP27 mRNA. On the contrary, MTX had little effect on -induced formation of inositol phosphates, PKC activation and phosphorylations of
MAP kinases. Our results strongly suggest that MTX enhances -stimulated HSP27 induction at a point downstream from MAP kinases in osteoblasts.
Keywords
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Article info
Publication history
Published online: October 12, 2004
Accepted:
June 14,
2004
Received:
January 10,
2004
Identification
Copyright
© 2004 Elsevier Ltd. Published by Elsevier Inc. All rights reserved.
