Heat shock protein 27 (HSPB1) suppresses the PDGF-BB-induced migration of osteoblasts

Kainuma,Shingo; Tokuda,Haruhiko; Yamamoto,Naohiro; Kuroyanagi,Gen; Fujita,Kazuhiko; Kawabata,Tetsu; Sakai,Go; Matsushima-Nishiwaki,Rie; Kozawa,Osamu; Otsuka,Takanobu

doi:10.3892/ijmm.2017.3119

Heat shock protein 27 (HSPB1) suppresses the PDGF-BB-induced migration of osteoblasts

Authors:
- Shingo Kainuma
- Haruhiko Tokuda
- Naohiro Yamamoto
- Gen Kuroyanagi
- Kazuhiko Fujita
- Tetsu Kawabata
- Go Sakai
- Rie Matsushima-Nishiwaki
- Osamu Kozawa
- Takanobu Otsuka
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Affiliations: Department of Orthopedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467-8601, Japan, Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan
Published online on: September 1, 2017 https://doi.org/10.3892/ijmm.2017.3119
Pages: 1057-1066
Copyright: © Kainuma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Heat shock protein 27 (HSP27/HSPB1), one of the small heat shock proteins, is constitutively expressed in various tissues. HSP27 and its phosphorylation state participate in the regulation of multiple physiological and pathophysiological cell functions. However, the exact roles of HSP27 in osteoblasts remain unclear. In the present study, we investigated the role of HSP27 in the platelet-derived growth factor‑BB (PDGF‑BB)‑stimulated migration of osteoblast-like MC3T3-E1 cells. PDGF-BB by itself barely upregulated the expression of HSP27 protein, but stimulated the phosphorylation of HSP27 in these cells. The PDGF-BB‑induced cell migration was significantly downregulated by HSP27 overexpression. The PDGF-BB-induced migrated cell numbers of the wild‑type HSP27-overexpressing cells and the phospho‑mimic HSP27-overexpressing (3D) cells were less than those of the unphosphorylatable HSP27-overexpressing (3A) cells. PD98059, an inhibitor of MEK1/2, SB203580, an inhibitor of p38 mitogen-activated protein kinase, and SP600125, an inhibitor of stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) reduced the PDGF-BB-induced migration of these cells, whereas Akt inhibitor or rapamycin, an inhibitor of upstream kinase of p70 S6 kinase (mTOR), barely affected the migration. However, the PDGF-BB-induced phosphorylation of p44/p42 MAPΚ, p38 MAPK and SAPK/JNK was not affected by HSP27 overexpression. There were no significant differences in the phosphorylation of p44/p42 MAPΚ, p38 MAP kinase or SAPK/JNK between the 3D cells and the 3A cells. These results strongly suggest that HSP27 functions as a negative regulator in the PDGF-BB-stimulated migration of osteoblasts, and the suppressive effect is amplified by the phosphorylation state of HSP27.

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