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Fibroblast growth factor-2 induces osteoblast survival through a phosphatidylinositol 3-kinase-dependent, -beta-catenin-independent signaling pathway.
Exp Cell Res. 2004 Jul 01; 297(1):235-46.EC

Abstract

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.

Authors+Show Affiliations

INSERM U 606, Lariboisière Hospital, Paris, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15194439

Citation

Debiais, F, et al. "Fibroblast Growth Factor-2 Induces Osteoblast Survival Through a Phosphatidylinositol 3-kinase-dependent, -beta-catenin-independent Signaling Pathway." Experimental Cell Research, vol. 297, no. 1, 2004, pp. 235-46.
Debiais F, Lefèvre G, Lemonnier J, et al. Fibroblast growth factor-2 induces osteoblast survival through a phosphatidylinositol 3-kinase-dependent, -beta-catenin-independent signaling pathway. Exp Cell Res. 2004;297(1):235-46.
Debiais, F., Lefèvre, G., Lemonnier, J., Le Mée, S., Lasmoles, F., Mascarelli, F., & Marie, P. J. (2004). Fibroblast growth factor-2 induces osteoblast survival through a phosphatidylinositol 3-kinase-dependent, -beta-catenin-independent signaling pathway. Experimental Cell Research, 297(1), 235-46.
Debiais F, et al. Fibroblast Growth Factor-2 Induces Osteoblast Survival Through a Phosphatidylinositol 3-kinase-dependent, -beta-catenin-independent Signaling Pathway. Exp Cell Res. 2004 Jul 1;297(1):235-46. PubMed PMID: 15194439.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fibroblast growth factor-2 induces osteoblast survival through a phosphatidylinositol 3-kinase-dependent, -beta-catenin-independent signaling pathway. AU - Debiais,F, AU - Lefèvre,G, AU - Lemonnier,J, AU - Le Mée,S, AU - Lasmoles,F, AU - Mascarelli,F, AU - Marie,P J, PY - 2003/12/09/received PY - 2004/02/24/revised PY - 2004/6/15/pubmed PY - 2004/8/13/medline PY - 2004/6/15/entrez SP - 235 EP - 46 JF - Experimental cell research JO - Exp Cell Res VL - 297 IS - 1 N2 - 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. SN - 0014-4827 UR - https://www.unboundmedicine.com/medline/citation/15194439/Fibroblast_growth_factor_2_induces_osteoblast_survival_through_a_phosphatidylinositol_3_kinase_dependent__beta_catenin_independent_signaling_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014482704001715 DB - PRIME DP - Unbound Medicine ER -