A calcium-induced signaling cascade leading to osteogenic differentiation of human bone marrow-derived mesenchymal stromal cells

被引：389

作者：

Barradas, Ana M. C. ^{[1
]}

Fernandes, Hugo A. M. ^{[1
]}

Groen, Nathalie ^{[1
]}

Chai, Yoke Chin ^{[2
,3
]}

Schrooten, Jan ^{[3
,4
]}

van de Peppel, Jeroen ^{[5
]}

van Leeuwen, Johannes P. T. M. ^{[5
]}

van Blitterswijk, Clemens A. ^{[1
]}

de Boer, Jan ^{[1
]}

机构：

[1] Univ Twente, MIRA Inst Biomed Technol & Tech Med, Dept Tissue Regenerat, NL-7522 NB Enschede, Netherlands

[2] Katholieke Univ Leuven, Lab Skeletal Dev & Joint Disorders, B-3000 Louvain, Belgium

[3] Katholieke Univ Leuven, Div Skeletal Tissue Engn, B-3000 Louvain, Belgium

[4] Katholieke Univ Leuven, Dept Met & Mat Engn, B-3001 Louvain, Belgium

[5] Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands

来源：

BIOMATERIALS | 2012年 / 33卷 / 11期

关键词：

Calcium phosphate; Stem cell; Bone morphogenetic protein; Osteogenesis; BETA-TRICALCIUM PHOSPHATE; EXTRACELLULAR CALCIUM; SENSING RECEPTOR; MORPHOGENETIC PROTEIN-2; IN-VITRO; OSTEOBLAST DIFFERENTIATION; GENE-EXPRESSION; STEM-CELLS; STRONTIUM RANELATE; HYDROXYAPATITE;

D O I：

10.1016/j.biomaterials.2012.01.020

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

The response of osteoprogenitors to calcium (Ca2+) is of primary interest for both normal bone homeostasis and the clinical field of bone regeneration. The latter makes use of calcium phosphate-based bone void fillers to heal bone defects, but it is currently not known how Ca2+ released from these ceramic materials influences cells in situ. Here, we have created an in vitro environment with high extracellular Ca2+ concentration and investigated the response of human bone marrow-derived mesenchymal stromal cells (hMSCs) to it. Ca2+ enhanced proliferation and morphological changes in hMSCs. Moreover, the expression of osteogenic genes is highly increased. A 3-fold up-regulation of BMP-2 is observed after only 6 h and pharmaceutical interference with a number of proteins involved in Ca2+ sensing showed that not the calcium sensing receptor, but rather type L voltage-gated calcium channels are involved in mediating the signaling pathway between extracellular Ca2+ and BMP-2 expression. MEK1/2 activity is essential for the effect of Ca2+ and using microarray analysis, we have identified c-Fos as an early Ca2+ response gene. We have demonstrated that hMSC osteogenesis can be induced via extracellular Ca2+, a simple and economic way of priming hMSCs for bone tissue engineering applications. (c) 2012 Elsevier Ltd. All rights reserved.

引用

页码：3205 / 3215

页数：11

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