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- Title
Signaling pathways implicated in PGF2α effects on Fgf2+/+ and Fgf2-/- osteoblasts.
- Authors
SABBIETI, MARIA GIOVANNA; AGAS, DIMITRIOS; MARCHETTI, LUIGI; SANTONI, GIORGIO; AMANTINI, CONSUELO; LIPING XIAO; MENGHI, GIOVANNA; HURLEY, MARJA M.
- Abstract
Prostaglandin F2α (PGF2α) regulates fibroblast growth factor-2 (FGF-2) and fibroblast growth factor receptor (FGFR) expression in osteoblasts. Here, the role of FGF-2 in PGF2α-induced proliferation and the signaling pathway involved, were determined in calvarial osteoblasts (COBs) from Fgf2+/+ and Fgf2-/- mice. The involvement of the exported FGF-2 isoform, was determined using the FGF-2 neutralizing antibody to alter its binding to FGFR1. PGF2α increased activity of Ras, and MAP-kinase cascade as well as Bcl-2 and c-Myc levels in Fgf2+/+ but not in Fgf2-/- COBs. Moreover, in Fgf2+/+ COBs, PGF2α-enhanced nuclear accumulation and co-localization of Bcl-2/c-Myc. Although up-regulation of multiple proliferative and survival signals were induced by PGF2α in Fgf2+/+ COBs, phospho-p53 was unmodified while p53 was increased. Increased phospho-p53 was, instead, found in Fgf2-/- COBs without up-regulation of oncogenic proteins. The lack of p53 activation in wild type osteoblasts could be due in part to the overexpression of MDM2 caused by PGF2α via FGF-2. PGF2α, also, increased cyclins D and E in Fgf2+/+ COBs and induced an expansion of Fgf2+/+ osteoblasts in G2/M phase. These data clearly show that PGF2α induces proliferation via endogenous FGF-2 and the exported isoform mediates PGF2α effects by acting in autocrine manner. Furthermore, silencing of FGFR1 in Fgf2+/+ COBs blocked PGF2α induced increase of phospho-MDM2 and cyclins. J. Cell. Physiol. 224: 465–474, 2010. © 2010 Wiley-Liss, Inc.
- Subjects
PROSTAGLANDINS; FIBROBLAST growth factors; BONE growth; BONE cells; MITOGEN-activated protein kinases
- Publication
Journal of Cellular Physiology, 2010, Vol 224, Issue 2, p465
- ISSN
0021-9541
- Publication type
Article
- DOI
10.1002/jcp.22143