title: FGF2 effects in periosteal fibroblasts bearing the FGFR2 receptor Pro253 Arg mutation.
abstract: OBJECTIVE
  A growing number of mutations mapped in the receptor gene for fibroblast growth factor have been implicated in several cranial development disorders including the Apert and Crouzon syndromes. The present paper investigated cellular mechanisms underlying Apert phenotype, by analyzing the effects of FGF2 in primary cultures of Apert periosteal fibroblasts carrying the FGFR2 Pro253Arg mutation.
  
  
  RESULTS
  FGF2 administration significantly decreased extracellular matrix production in mutant cells by stimulating degradative enzymatic activities. Gene expression analysis revealed that decorin and biglycan, two proteoglycans involved in collagen fibrillogenesis, were more expressed in mutant cells and down-regulated by FGF2. FGF2 receptor binding showed little differences in high affinity receptor counts between mutant and wild-type cells, while we showed for the first time that low affinity receptors are significantly fewer in mutant cells. Differences were found in Crouzon syndrome, where both high and low affinity receptor counts were up-regulated.
  
  
  CONCLUSIONS
  The different mutation and low affinity receptor regulation in mutant receptors support the hypothesis that the impact on the activity of the ligand-receptor complex could allow distinct modes of FGF2 activation in Apert and Crouzon syndromes, which interfere with the FGFR2 signalling cascade.
authors.affiliation: Department of Exp. Med. and Bioch. Sciences, University of Perugia, via del Giochetto, 06100 Perugia, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Lilli
authors.forename: Catia
authors.initials: C
authors.lastname: Bellucci
authors.forename: Tiziano
authors.initials: T
authors.lastname: Baroni
authors.forename: Cristina
authors.initials: C
authors.lastname: Aisa
authors.forename: Paolo
authors.initials: P
authors.lastname: Carinci
authors.forename: Luca
authors.initials: L
authors.lastname: Scapoli
authors.forename: Francesco
authors.initials: F
authors.lastname: Carinci
authors.forename: Furio
authors.initials: F
authors.lastname: Pezzetti
authors.forename: Eleonora
authors.initials: E
authors.lastname: Lumare
authors.forename: Giordano
authors.initials: G
authors.lastname: Stabellini
authors.forename: Maria
authors.initials: M
authors.lastname: Bodo
mesh_terms: D000168:Acrocephalosyndactylia / Q000235:genetics* / Q000378:metabolism; D000293:Adolescent; D001120:Arginine / Q000737:chemistry / Q000235:genetics; D002452:Cell Count; D024042:Collagen Type I / Q000378:metabolism; D003394:Craniofacial Dysostosis / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D005109:Extracellular Matrix / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism* / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D006026:Glycoside Hydrolases / Q000378:metabolism; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D010447:Peptide Hydrolases / Q000378:metabolism; D010521:Periosteum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010641:Phenotype; D011392:Proline / Q000737:chemistry / Q000235:genetics; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000819:agonists / Q000235:genetics / Q000378:metabolism*
chemical_list: D024042:Collagen Type I; D005353:Fibronectins; D011509:Proteoglycans; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; D001120:Arginine; D011392:Proline; D051497:Receptor, Fibroblast Growth Factor, Type 2; D006026:Glycoside Hydrolases; D010447:Peptide Hydrolases; D020781:Matrix Metalloproteinase 1