Fibroblast growth factor-2 induces osteoblast survival through a phosphatidylinositol 3-kinase-dependent, -β-catenin-independent signaling pathway
| Autor: | G Lefèvre, F Debiais, F. Lasmoles, Frédéric Mascarelli, S. Le Mée, Pierre J. Marie, Jérome Lemonnier |
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| Rok vydání: | 2004 |
| Předmět: |
Cell Survival
Lymphoid Enhancer-Binding Factor 1 p38 mitogen-activated protein kinases Apoptosis Lithium Biology Fibroblast growth factor Glycogen Synthase Kinase 3 Phosphatidylinositol 3-Kinases Osteogenesis medicine Humans Enzyme Inhibitors Phosphorylation Protein kinase B Cells Cultured beta Catenin PI3K/AKT/mTOR pathway Cell Line Transformed Phosphoinositide-3 Kinase Inhibitors Feedback Physiological Osteoblasts Caspase 3 Kinase Caspase 2 Osteoblast Blood Proteins Cell Biology Caspase Inhibitors Up-Regulation Cell biology DNA-Binding Proteins Cytoskeletal Proteins medicine.anatomical_structure Caspases Trans-Activators Fibroblast Growth Factor 2 Signal transduction Signal Transduction Transcription Factors |
| Zdroj: | Experimental Cell Research. 297:235-246 |
| ISSN: | 0014-4827 |
| DOI: | 10.1016/j.yexcr.2004.03.032 |
| Popis: | Fibroblast growth factor-2 (FGF-2) is an important molecule that controls bone formation through activation of osteoblastic cell replication and differentiation. The role of FGF-2 on human osteoblast survival and the signaling pathway that mediates its effect are not known. We studied the effect of FGF-2 on apoptosis induced by low serum concentration and the signal transduction pathway involved in this effect in human primary calvaria osteoblasts and immortalized osteoblastic cells. Treatment with FGF-2 for 24-48 h protected against osteoblast apoptosis induced by low serum concentration, through specific inhibition of caspase-2 and caspase-3 activity. Pharmacological inhibition of MEK-1 and p38 MAPK had no effect on the inhibition of caspases-2 and -3 induced by FGF-2. In contrast, inhibition of PI3K with LY294002 abolished the FGF-2-induced inhibition of caspases-2 and -3. FGF-2 increased PI3K activity but did not induce phosphorylation of Akt or the downstream effector p70 S6 kinase. FGF-2 also induced GSK-3alpha and beta phosphorylation in osteoblastic cells, which however did not result in beta-catenin accumulation or Lef/Tcf transcriptional activity. In contrast, lithium induced beta-catenin accumulation, Lef/Tcf transcriptional activation and increased caspase-2 and -3 activity. The results indicate that the immediate protective effect of FGF-2 on human osteoblastic cell apoptosis involves PI3K and inhibition of downstream caspases, independently of GSK-3 and beta-catenin-Lef/Tcf-mediated transcription. |
| Databáze: | OpenAIRE |
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