Prostaglandin F2alpha involves heparan sulphate sugar chains and FGFRs to modulate osteoblast growth and differentiation.
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.
Sabbieti
Maria Giovanna
MG
Department of Comparative Morphology and Biochemistry, University of Camerino, Camerino (MC), Italy.
Agas
Dimitrios
D
Materazzi
Stefano
S
Capacchietti
Mariolina
M
Materazzi
Giovanni
G
Hurley
Marja M
MM
Menghi
Giovanna
G
Marchetti
Luigi
L
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
D019812:Heparan Sulfate Proteoglycans; D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; D015237:Dinoprost; D048049:Extracellular Signal-Regulated MAP Kinases