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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Buchner, Johannes / Ludwig, Stephan / Sies, Helmut / Turk, Boris / Wittinghofer, Alfred

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Could the effect of modeled microgravity on osteogenic differentiation of human mesenchymal stem cells be reversed by regulation of signaling pathways?

Qiang Zheng1 / Guoping Huang2 / Jinfeng Yang3 / Yulin Xu4 / Chunjuan Guo5 / Yongmei Xi6 / Zhijun Pan7 / Jinfu Wang8

1Department of Cell Biology, College of Life Science, Zhejiang University, Hangzhou, Zhejiang 310058, P.R. China and The Second Hospital, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China
The first two authors contributed equally to this work.

2Department of Cell Biology, College of Life Science, Zhejiang University, Hangzhou, Zhejiang 310058, P.R. China
The authors 1 and 2 contributed equally to this work.

3Department of Cell Biology, College of Life Science, Zhejiang University, Hangzhou, Zhejiang 310058, P.R. China

4Department of Cell Biology, College of Life Science, Zhejiang University, Hangzhou, Zhejiang 310058, P.R. China

5Department of Cell Biology, College of Life Science, Zhejiang University, Hangzhou, Zhejiang 310058, P.R. China

6Department of Cell Biology, College of Life Science, Zhejiang University, Hangzhou, Zhejiang 310058, P.R. China

7The Second Hospital, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China

8Department of Cell Biology, College of Life Science, Zhejiang University, Hangzhou, Zhejiang 310058, P.R. China

Corresponding author

Citation Information: Biological Chemistry. Volume 388, Issue 7, Pages 755–763, ISSN (Online) 14316730, ISSN (Print) 14374315, DOI: 10.1515/BC.2007.082, July 2007

Publication History

Received:
2007-01-08
Accepted:
2007-04-05
Published Online:
2007-07-01

Abstract

Microgravity (MG) results in a reduction in bone formation. Bone formation involves osteogenic differentiation from mesenchymal stem cells (hMSCs) in bone marrow. We modeled MG to determine its effects on osteogenesis of hMSCs and used activators or inhibitors of signaling factors to regulate osteogenic differentiation. Under osteogenic induction, MG reduced osteogenic differentiation of hMSCs and decreased the expression of osteoblast gene markers. The expression of Runx2 was also inhibited, whereas the expression of PPARγ2 increased. MG also decreased phosphorylation of ERK, but increased phosphorylation of p38MAPK. SB203580, a p38MAPK inhibitor, was able to inhibit the phosphorylation of p38MAPK, but did not reduce the expression of PPARγ2. Bone morphogenetic protein (BMP) increased the expression of Runx2. Fibroblast growth factor 2 (FGF2) increased the phosphorylation of ERK, but did not significantly increase the expression of osteoblast gene markers. The combination of BMP, FGF2 and SB203580 significantly reversed the effect of MG on osteogenic differentiation of hMSCs. Our results suggest that modeled MG inhibits the osteogenic differentiation and increases the adipogenic differentiation of hMSCs through different signaling pathways. Therefore, the effect of MG on the differentiation of hMSCs could be reversed by the mediation of signaling pathways.

Keywords: adipogenesis; human mesenchymal stem cells; microgravity; osteogenesis; signaling pathways

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