Rho-kinase regulates prostaglandin D2-stimulated heat shock protein 27 induction in osteoblasts

Kato,Kenji; Tokuda,Haruhiko; Natsume,Hideo; Adachi,Seiji; Matsushima-Nishiwaki,Rie; Minamitani,Chiho; Mizutani,Jun; Kozawa,Osamu; Otsuka,Takanobu

doi:10.3892/etm_00000091

Rho-kinase regulates prostaglandin D2-stimulated heat shock protein 27 induction in osteoblasts

Authors:
- Kenji Kato
- Haruhiko Tokuda
- Hideo Natsume
- Seiji Adachi
- Rie Matsushima-Nishiwaki
- Chiho Minamitani
- Jun Mizutani
- Osamu Kozawa
- Takanobu Otsuka
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Affiliations: Department of Orthopedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan
Published online on: July 1, 2010 https://doi.org/10.3892/etm_00000091
Pages: 579-583

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Abstract

We previously reported that prostaglandin D2 (PGD2) stimulates heat shock protein 27 (HSP27) induction through p44/p42 mitogen-activated protein (MAP) kinase, p38 MAP kinase and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in osteoblast-like MC3T3-E1 cells. In addition, we recently showed that PGD2 activates Rho-kinase, resulting in the regulation of interleukin-6 synthesis via activation of p38 MAP kinase but not p44/p42 MAP kinase in these cells. In the present study, in order to investigate whether Rho-kinase is involved in the PGD2-stimulated HSP27 induction in MC3T3-E1 cells, we examined the effects of Rho-kinase inhibitors on HSP27 induction. Y27632 and fasudil, Rho-kinase inhibitors, markedly suppressed the HSP27 induction stimulated by PGD2 in a dose-dependent manner without affecting levels of HSP70 in the presence of PGD2. Immunofluorescence microscopy studies also revealed that Y27632 and fasudil markedly suppressed the induction of HSP27. Y27632 and fasudil attenuated the PGD2-induced phosphorylation levels of SAPK/JNK. In conclusion, Rho-kinase inhibitors regulate PGD2-stimulated HSP27 induction via activation of both SAPK/JNK and p38 MAP kinase in osteoblasts.

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