title: Prostaglandin F2alpha involves heparan sulphate sugar chains and FGFRs to modulate osteoblast growth and differentiation.
abstract: The present investigation extends our previous studies on PGF2alpha-mediated signalling in osteoblast metabolism. In particular, the role of PGF2alpha as modulator of heparan sulphate proteoglycans (HSPGs), fibroblast growth factor 2 (FGF-2) and fibroblast growth factor receptors (FGFRs) was evaluated. We hereby reported the novel observation that PGF2alpha was able to promote the formation of HSPGs/FGF-2/FGFRs complexes. Moreover, our data suggested that PGF2alpha could induce new synthesis of heparan sulphate (HS) chains on osteoblasts by a mechanism involving a modulation of MAPK signalling and that HS is required for the regulation of FGF-2 induced by PGF2alpha. Indeed, a proteolytic cleavage of HSPGs with heparinase III (Hep III) prior to PGF2alpha administration down-regulated the basal expression of phospho-p44/42, likely inhibiting FGFRs tyrosine kinase activity. Interestingly, MAPK signalling influenced syntheses and subcellular localization of FGF-2, its specific receptor and HS. In addition, the proteolytic cleavage by Hep III and the MAPK kinase inhibition by PD-98059 also revealed that PGF2alpha induced cell proliferation is dependent on HSPGs and FGF-2 specific receptor, respectively. Of further relevance of this study, we demonstrated, by using a specific siRNA for FGFR1, that PGF2alpha modulates Runx2 expression by FGFR1 and HS.
authors.affiliation: Department of Comparative Morphology and Biochemistry, University of Camerino, Camerino (MC), Italy.
authors.forename: Maria Giovanna
authors.initials: MG
authors.lastname: Sabbieti
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Agas
authors.forename: Stefano
authors.initials: S
authors.lastname: Materazzi
authors.forename: Mariolina
authors.initials: M
authors.lastname: Capacchietti
authors.forename: Giovanni
authors.initials: G
authors.lastname: Materazzi
authors.forename: Marja M
authors.initials: MM
authors.lastname: Hurley
authors.forename: Giovanna
authors.initials: G
authors.lastname: Menghi
authors.forename: Luigi
authors.initials: L
authors.lastname: Marchetti
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D015237:Dinoprost / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism*; D008297:Male; D051379:Mice; D018613:Microscopy, Confocal; D016253:Microscopy, Immunoelectron; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism*; D034622:RNA Interference; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D019812:Heparan Sulfate Proteoglycans; D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; D015237:Dinoprost; D048049:Extracellular Signal-Regulated MAP Kinases