Notch signaling pathway and gene expression profiles during early in vitro differentiation of liver-derived mesenchymal stromal cells to osteoblasts
| Autor: | Marta Lesiak, Wirginia Likus, Damian Kusz, Halina Koryciak-Komarska, Piotr Czekaj, Daniel Krakowian, Ksymena Urbanek, Aleksander Sieroń |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Stromal cell Liver cytology Cellular differentiation Notch signaling pathway Pathology and Forensic Medicine Rats Sprague-Dawley 03 medical and health sciences Osteogenesis Animals Receptor Molecular Biology Notch 1 Cells Cultured Osteoblasts Receptors Notch Chemistry Gene Expression Profiling Mesenchymal stem cell Cell Differentiation Mesenchymal Stem Cells Cell Biology Cell biology Rats 030104 developmental biology Liver Signal transduction Signal Transduction |
| Zdroj: | Laboratory investigation; a journal of technical methods and pathology. 97(10) |
| ISSN: | 1530-0307 |
| Popis: | Notch signaling is a key signaling pathway for cell proliferation and differentiation. Therefore, we formulated a working hypothesis that Notch signaling can be used to detect early osteoblastic differentiation of mesenchymal stromal cells. Changes in expression and distribution of Notch 1, 2, 3, and Delta1 in the cytoplasm and nuclei of rat liver-derived mesenchymal stromal cells differentiating into osteoblasts were investigated, together with the displacement of intracellular domains (ICDs) of the receptors. In addition, an oligonucleotide microarray was used to determine the expression of genes known to be linked to selected signaling pathways. Statistically significant changes in the number of cells expressing Notch1, Notch2, and Delta1, but not Notch3, and their activated forms were detected within 24 h of culture under osteogenic conditions. Although the number of cells expressing Notch3 remained unchanged, the number of cells with the activated receptor was significantly elevated. The number of cells positive for Notch3 was higher than that for the other Notch receptors even after 48 h of differentiation; however, a smaller fraction of cells contained activated Notch3. Culture mineralization was detected on day 4 of differentiation, and all analyzed receptors were present in the cells at that time, but only Delta1 was activated in twice as many cells than that before differentiation. Thus, the three analyzed receptors and ligand can serve as markers of very early stages of osteogenesis in stromal cells. These early changes in activation of the Notch signaling pathway were correlated with the transcription of several genes linked to osteogenesis, such as Bmps, Mmps, and Egfr, and with the regulation of cell cycle and apoptosis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink