Change in hepatocyte growth factor concentration promote mesenchymal stem cell‐mediated osteogenic regeneration

Journal of Cellular and Molecular Medicine

Qian Wen¹  Liang Zhou²  Chaoying Zhou¹  Mingqian Zhou¹  Wei Luo¹ 

[1] Institute of Molecular Immunology, School of Biotechnology, Southern Medical University, Guangzhou, China;Department of Obstetrics & Gynaecology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China

关键词: hepatocyte growth factor;    mesenchymal stem cells;    proliferation;    osteogenic differentiation;    avascular necrosis of femoral head;   

DOI  :  10.1111/j.1582-4934.2011.01407.x

来源: Wiley

【 摘 要 】

Abstract

Mesenchymal stem cells (MSCs) play a crucial role in tissue repair by secretion of tissue nutrient factors such as hepatocyte growth factor (HGF). However, studies examining the effects of HGF on the proliferation and differentiation of MSCs used different concentrations of HGF and reported conflicting conclusions. This study aimed to determine the mechanisms by which different concentrations of HGF regulate MSC proliferation and osteogenic differentiation, and validate the mechanism in an animal model of early stage avascular necrosis of femoral head (ANFH). Our results demonstrate that a low concentration of HGF (20 ng/ml) preferentially promotes MSC osteogenic differentiation through increased c-Met expression and phosphorylation, Akt pathway activation, and increased expression of p27, Runx2 and Osterix. In contrast, a high concentration of HGF (100 ng/ml) strongly induced proliferation by inducing strong activation of the ERK1/2 signalling pathway. As validated by animal experiments, high localized expression of HGF achieved by transplantation of HGF transgenic MSCs into ANFH rabbits increased the number of MSCs. Subsequently, 2 weeks after transplantation, HGF levels decreased and MSCs differentiated into osteoblasts and resulted in efficient tissue repair. Our results demonstrate that sequential concentration changes in HGF control the proliferation and osteogenic differentiation of MSCs in vivo. This phenomenon can be exploited therapeutically to induce bone regeneration and, in turn, improve the efficacy of pharmacological intervention for ANFH treatment.

【 授权许可】

Unknown   
© 2011 The Authors Journal compilation © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd