Could the effect of modeled microgravity on osteogenic differentiation of human mesenchymal stem cells be reversed by regulation of signaling pathways?
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Qiang Zheng
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.
©2007 by Walter de Gruyter Berlin New York
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- 25 years of catalytic RNA: looking younger than ever!
- On the occasion of the 25th anniversary of the discovery of catalytic RNA
- An overview of the RNA world – for now
- Group II introns: structure, folding and splicing mechanism
- Expression of protein-coding genes embedded in ribosomal DNA
- Importance of tRNA interactions with 23S rRNA for peptide bond formation on the ribosome: studies with substrate analogs
- The spliceosome: a ribozyme at heart?
- A chemo-genetic approach for the study of nucleobase participation in nucleolytic ribozymes
- Long-range impact of peripheral joining elements on structure and function of the hepatitis delta virus ribozyme
- A 2′-methyl or 2′-methylene group at G+1 in precursor tRNA interferes with Mg2+ binding at the enzyme-substrate interface in E-S complexes of E. coli RNase P
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