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HSP70 Inhibitors Reduce The Osteoblast Migration By Epidermal Growth Factor

[ Vol. 18 , Issue. 7 ]

Author(s):

Tetsu Kawabata, Takanobu Otsuka, Kazuhiko Fujita, Go Sakai, Woo Kim, Rie Matsushima-Nishiwaki, Gen Kuroyanagi, Osamu Kozawa* and Haruhiko Tokuda   Pages 486 - 495 ( 10 )

Abstract:


Background: We have recently reported that epidermal growth factor (EGF) induces migration of osteoblast-like MC3T3-E1 cells through the activation of p44/p42 mitogen-activated protein (MAP) kinase, p38 MAP kinase, stress-activated protein kinase/ c-Jun N-terminal kinase (SAPK/JNK) and Akt. Furthermore, we demonstrated that heat shock protein 70 (HSP70) down-regulates the transforming growth factor-β- stimulated vascular endothelial growth factor synthesis via suppression of p38 MAP kinase in osteoblast-like MC3T3-E1 cells. However, the exact role of HSP70 underlying osteoblast migration is not fully elucidated.

Objective: The aim of this study is to investigate the effects of HSP70 inhibitors on the EGF-stimulated osteoblast migration, and the underlying mechanism.

Methods: Osteoblast-like MC3T3-E1 cells were treated with two types of HSP70 inhibitors, VER-155008 or YM-08. Transwell cell migration assay and wound-healing assay were analyzed for osteoblast migration. The expression levels of HSP70 and the phosphorylation of p38 MAP kinase, p44/p42 MAP kinase, SAPK/JNK or Akt were evaluated by a Western blot analysis.

Results: EGF hardly affected the expression levels of HSP70 at the present or absent of VER-155008. EGF-stimulated migration was significantly reduced by both HSP70 inhibitors, VER-155008 and YM-08, determined by a transwell cell migration assay. The suppressive effects of both HSP70 inhibitors on the migration stimulated by EGF were also observed by a wound-healing assay. VER-155008 inhibited the EGF-induced phosphorylation of p44/p42 MAP kinase and AKT, but not p38 MAP kinase or SAPK/JNK.

Conclusion: This study provides new evidence that HSP70 inhibitors reduce the EGFstimulated migration of osteoblasts through the suppression of p44/p42 MAP kinase and Akt.

Keywords:

HSP70, EGF, migration, p44/p42 MAP kinase, Akt, osteoblast.

Affiliation:

Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu, Department of Orthopedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu, Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu, Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu, Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu, Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu, Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu, Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu



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