HSP70 Inhibitors Reduce The Osteoblast Migration By Epidermal Growth Factor

Author(s): Tetsu Kawabata, Takanobu Otsuka, Kazuhiko Fujita, Go Sakai, Woo Kim, Rie Matsushima-Nishiwaki, Gen Kuroyanagi, Osamu Kozawa*, Haruhiko Tokuda

Journal Name: Current Molecular Medicine

Volume 18 , Issue 7 , 2018

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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.

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Article Details

Year: 2018
Published on: 30 January, 2019
Page: [486 - 495]
Pages: 10
DOI: 10.2174/1566524019666181213112847
Price: $65

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