Could the effect of modeled microgravity on osteogenic differentiation of human mesenchymal stem cells be reversed by regulation of signaling pathways?
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.
Zheng
Qiang
Q
Department of Cell Biology, College of Life Science, Zhejiang University, Hangzhou, Zhejiang, PR China.
Huang
Guoping
G
Yang
Jinfeng
J
Xu
Yulin
Y
Guo
Chunjuan
C
Xi
Yongmei
Y
Pan
Zhijun
Z
Wang
Jinfu
J
D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers; D002454:Cell Differentiation; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D050356:Lipid Metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D008954:Models, Biological; D010012:Osteogenesis; D047495:PPAR gamma / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D015398:Signal Transduction; D014893:Weightlessness
D015415:Biomarkers; D050659:Core Binding Factor Alpha 1 Subunit; D047495:PPAR gamma; D012333:RNA, Messenger; D000469:Alkaline Phosphatase