模拟微重力对人间充质干细胞成骨分化的影响能否通过信号通路的调节来逆转？

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

作者信息

Zheng Qiang, Huang Guoping, Yang Jinfeng, Xu Yulin, Guo Chunjuan, Xi Yongmei, Pan Zhijun, Wang Jinfu

机构信息

Department of Cell Biology, College of Life Science, Zhejiang University, Hangzhou, Zhejiang, PR China.

出版信息

Biol Chem. 2007 Jul;388(7):755-63. doi: 10.1515/BC.2007.082.

DOI:10.1515/BC.2007.082

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 PPARgamma2 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 PPARgamma2. 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.

摘要

微重力（MG）会导致骨形成减少。骨形成涉及骨髓中间充质干细胞（hMSCs）的成骨分化。我们模拟微重力以确定其对hMSCs成骨的影响，并使用信号因子的激活剂或抑制剂来调节成骨分化。在成骨诱导下，微重力降低了hMSCs的成骨分化，并降低了成骨细胞基因标志物的表达。Runx2的表达也受到抑制，而PPARgamma2的表达增加。微重力还降低了ERK的磷酸化，但增加了p38MAPK的磷酸化。p38MAPK抑制剂SB203580能够抑制p38MAPK的磷酸化，但并未降低PPARgamma2的表达。骨形态发生蛋白（BMP）增加了Runx2的表达。成纤维细胞生长因子2（FGF2）增加了ERK的磷酸化，但并未显著增加成骨细胞基因标志物的表达。BMP、FGF2和SB203580的组合显著逆转了微重力对hMSCs成骨分化的影响。我们的结果表明，模拟微重力通过不同的信号通路抑制hMSCs的成骨分化并增加其成脂分化。因此，微重力对hMSCs分化的影响可通过信号通路的介导而逆转。