RÉSUMÉ
Dlx3 and Dlx5 are homeobox domain proteins and are well-known regulators of osteoblastic differentiation. Since possible reciprocal relationships between osteogenic and adipogenic differentiation in mesenchymal stem cells exist, we examined the regulatory role of Dlx3 and Dlx5 on adipogenic differentiation using human dental pulp stem cells. Over-expression of Dlx3 and Dlx5 stimulated osteogenic differentiation but inhibited adipogenic differentiation of human dental pulp stem cells. Dlx3 and Dlx5 suppressed the expression of adipogenic marker genes such as C/EBPalpha, PPARgamma, aP2 and lipoprotein lipase. Adipogenic stimuli suppressed the mRNA levels of Dlx3 and Dlx5, whereas osteogenic stimuli enhanced the expression of Dlx3 and Dlx5 in 3T3-L1 preadipocytes. These results suggest that Dlx3 and Dlx5 exert a stimulatory effect on osteogenic differentiation of stem cells through the inhibition of adipogenic differentiation as well as direct stimulation.
Sujet(s)
Humains , Pulpe dentaire , Durapatite , Gènes homéotiques , Lipoprotein lipase , Cellules souches mésenchymateuses , Ostéoblastes , Récepteur PPAR gamma , Protéines , ARN messager , Cellules souchesRÉSUMÉ
Sphingosine-1-phosphate (S1P), a bioactive sphingolipid metabolite, has various functions to affect many signalling pathways leading to cellular proliferation and differentiation and to regulate of cell migration, invasion, and angiogenesis. However, there are little reports about the relation between trophoblast stem cells and S1P. Thus, the physiologic effects of S1P on trophoblast stem (TS) cells were investigated in this study. S1P was involved in early stage development of trophoblast via upregulation of Eomesodermine mRNA expression and suppressed differentiation of TS cells through activation of extracellular-signal regulated kinase (ERK) activation. Other actions of S1P were the activation of p38 and the induction of Dlx-3 mRNA expression for angiogenesis in TS cells. Interestingly, TS cells cultured with S1P for 4 days in thrombin-fibrinogen gel culture system, specific culture system for endothelial cells, showed good healthy appearance, but TS cells cultured without S1P got severe damages. Taken together, we suggest that S1P has very important roles on placenta such as development of early stage trophoblast, suppression of differentiation, and angiogenesis on placenta.