Extracellular heat shock protein 70 promotes osteogenesis of human mesenchymal stem cells through activation of the ERK signaling pathway

Erman Chen; Deting Xue; Wei Zhang; Feng Lin; Zhijun Pan

doi:10.1016/j.febslet.2015.11.021

Extracellular heat shock protein 70 promotes osteogenesis of human mesenchymal stem cells through activation of the ERK signaling pathway

FEBS Lett. 2015 Dec 21;589(24 Pt B):4088-96. doi: 10.1016/j.febslet.2015.11.021. Epub 2015 Nov 19.

Authors

Erman Chen¹, Deting Xue¹, Wei Zhang¹, Feng Lin¹, Zhijun Pan²

Affiliations

¹ Department of Orthopedics, Second Affiliated Hospital, School of Medicine, Zhejiang University, 310000 Hangzhou, People's Republic of China.
² Department of Orthopedics, Second Affiliated Hospital, School of Medicine, Zhejiang University, 310000 Hangzhou, People's Republic of China. Electronic address: chenerman_zju@163.com.

PMID: 26608032
DOI: 10.1016/j.febslet.2015.11.021

Abstract

Heat shock proteins have protective effects when cells are exposed to stress. However, the relationship between extracellular heat shock protein 70 (eHSP70) and osteogenesis of hMSCs has not been reported. The results of this study showed that HSP70 (200 ng/ml) increases alkaline phosphatase activity and promotes hMSC mineralization. Under osteogenic induction conditions, HSP70 significantly upregulated the expression of osteo-specific genes, such as the runt family transcription factor Runx2 and osterix (OSX). Comparative expression profiling by microarray and pathway analyses revealed that HSP70 promotes osteogenesis of hMSCs through activation of the ERK signaling pathway. HSP70 may be a potential therapeutic agent for the treatment of bone nonunion.

Keywords: Bone nonunion; ERK signaling pathway; Extracellular HSP70; Human mesenchymal stem cell; Osteogenesis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alkaline Phosphatase / chemistry
Alkaline Phosphatase / metabolism
Biomarkers / metabolism
Butadienes / pharmacology
Calcification, Physiologic / drug effects
Cell Line
Core Binding Factor Alpha 1 Subunit / agonists
Core Binding Factor Alpha 1 Subunit / genetics
Core Binding Factor Alpha 1 Subunit / metabolism
Extracellular Space
Gene Expression Profiling
Gene Expression Regulation, Developmental / drug effects
HSP70 Heat-Shock Proteins / metabolism*
Humans
MAP Kinase Signaling System* / drug effects
Mesenchymal Stem Cells / cytology
Mesenchymal Stem Cells / drug effects
Mesenchymal Stem Cells / metabolism*
Nitriles / pharmacology
Oligonucleotide Array Sequence Analysis
Osteogenesis* / drug effects
Phosphorylation / drug effects
Protein Kinase Inhibitors / pharmacology
Protein Processing, Post-Translational / drug effects
Sp7 Transcription Factor
Transcription Factors / agonists
Transcription Factors / genetics
Transcription Factors / metabolism
Up-Regulation* / drug effects

Substances

Biomarkers
Butadienes
Core Binding Factor Alpha 1 Subunit
HSP70 Heat-Shock Proteins
Nitriles
Protein Kinase Inhibitors
RUNX2 protein, human
Sp7 Transcription Factor
SP7 protein, human
Transcription Factors
U 0126
Alkaline Phosphatase