HSP70 Inhibitor Suppresses IGF-I-Stimulated Migration of Osteoblasts through p44/p42 MAP Kinase

Heat shock protein 70 (HSP70) is a ubiquitously expressed molecular chaperone in a variety of cells including osteoblasts. We previously showed that insulin-like growth factor-I (IGF-I) elicits migration of osteoblast-like MC3T3-E1 cells through the activation of phosphatidylinositol 3-kinase/Akt an...

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Autores principales: Kawabata, Tetsu, Tokuda, Haruhiko, Sakai, Go, Fujita, Kazuhiko, Matsushima-Nishiwaki, Rie, Kuroyanagi, Gen, Otsuka, Takanobu, Kozawa, Osamu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6316248/
https://www.ncbi.nlm.nih.gov/pubmed/30469446
http://dx.doi.org/10.3390/biomedicines6040109
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author Kawabata, Tetsu
Tokuda, Haruhiko
Sakai, Go
Fujita, Kazuhiko
Matsushima-Nishiwaki, Rie
Kuroyanagi, Gen
Otsuka, Takanobu
Kozawa, Osamu
author_facet Kawabata, Tetsu
Tokuda, Haruhiko
Sakai, Go
Fujita, Kazuhiko
Matsushima-Nishiwaki, Rie
Kuroyanagi, Gen
Otsuka, Takanobu
Kozawa, Osamu
author_sort Kawabata, Tetsu
collection PubMed
description Heat shock protein 70 (HSP70) is a ubiquitously expressed molecular chaperone in a variety of cells including osteoblasts. We previously showed that insulin-like growth factor-I (IGF-I) elicits migration of osteoblast-like MC3T3-E1 cells through the activation of phosphatidylinositol 3-kinase/Akt and p44/p42 mitogen-activated protein (MAP) kinase. In the present study, we investigated the effects of HSP70 inhibitors on the IGF-I-elicited migration of these cells and the mechanism involved. The IGF-I-stimulated osteoblast migration evaluated by a wound-healing assay and by a transwell cell migration was significantly reduced by VER-155008 and YM-08, which are both HSP70 inhibitors. VER-155008 markedly suppressed the IGF-I-induced phosphorylation of p44/p42 MAP kinase without affecting that of Akt. In conclusion, our results strongly suggest that the HSP70 inhibitor reduces the IGF-I-elicited migration of osteoblasts via the p44/p42 MAP kinase.
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spelling pubmed-63162482019-01-10 HSP70 Inhibitor Suppresses IGF-I-Stimulated Migration of Osteoblasts through p44/p42 MAP Kinase Kawabata, Tetsu Tokuda, Haruhiko Sakai, Go Fujita, Kazuhiko Matsushima-Nishiwaki, Rie Kuroyanagi, Gen Otsuka, Takanobu Kozawa, Osamu Biomedicines Article Heat shock protein 70 (HSP70) is a ubiquitously expressed molecular chaperone in a variety of cells including osteoblasts. We previously showed that insulin-like growth factor-I (IGF-I) elicits migration of osteoblast-like MC3T3-E1 cells through the activation of phosphatidylinositol 3-kinase/Akt and p44/p42 mitogen-activated protein (MAP) kinase. In the present study, we investigated the effects of HSP70 inhibitors on the IGF-I-elicited migration of these cells and the mechanism involved. The IGF-I-stimulated osteoblast migration evaluated by a wound-healing assay and by a transwell cell migration was significantly reduced by VER-155008 and YM-08, which are both HSP70 inhibitors. VER-155008 markedly suppressed the IGF-I-induced phosphorylation of p44/p42 MAP kinase without affecting that of Akt. In conclusion, our results strongly suggest that the HSP70 inhibitor reduces the IGF-I-elicited migration of osteoblasts via the p44/p42 MAP kinase. MDPI 2018-11-21 /pmc/articles/PMC6316248/ /pubmed/30469446 http://dx.doi.org/10.3390/biomedicines6040109 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kawabata, Tetsu
Tokuda, Haruhiko
Sakai, Go
Fujita, Kazuhiko
Matsushima-Nishiwaki, Rie
Kuroyanagi, Gen
Otsuka, Takanobu
Kozawa, Osamu
HSP70 Inhibitor Suppresses IGF-I-Stimulated Migration of Osteoblasts through p44/p42 MAP Kinase
title HSP70 Inhibitor Suppresses IGF-I-Stimulated Migration of Osteoblasts through p44/p42 MAP Kinase
title_full HSP70 Inhibitor Suppresses IGF-I-Stimulated Migration of Osteoblasts through p44/p42 MAP Kinase
title_fullStr HSP70 Inhibitor Suppresses IGF-I-Stimulated Migration of Osteoblasts through p44/p42 MAP Kinase
title_full_unstemmed HSP70 Inhibitor Suppresses IGF-I-Stimulated Migration of Osteoblasts through p44/p42 MAP Kinase
title_short HSP70 Inhibitor Suppresses IGF-I-Stimulated Migration of Osteoblasts through p44/p42 MAP Kinase
title_sort hsp70 inhibitor suppresses igf-i-stimulated migration of osteoblasts through p44/p42 map kinase
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6316248/
https://www.ncbi.nlm.nih.gov/pubmed/30469446
http://dx.doi.org/10.3390/biomedicines6040109
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