Source:http://linkedlifedata.com/resource/pubmed/id/20489451
Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
|
| pubmed:dateCreated |
2010-5-21
|
| pubmed:abstractText |
Mutations in fibroblast growth factor receptor 2 (FGFR2), a transmembrane receptor expressed in suture mesenchyme, osteogenic fronts, and dura, have been implicated in the etiopathogenesis of craniosynostosis syndromes. The C278F- and P253R-FGFR2 mutations result in Crouzon and Apert syndromes, respectively. The dura mater plays a critical role in the formation and maintenance of cranial sutures. However, its role in syndromic craniosynostosis remains unclear. This study examines the influence of FGFR2 mutations in dural cells on osteoblast proliferation and differentiation. Primary cultures of dural cells and osteoblasts were established, and adenoviral-FGFR2 constructs were prepared by subcloning mutant (C278F and P253R) FGFR2 constructs into adenovirus. Dural cells were infected with adenovirus, and dural protein expression was confirmed by immunostaining. Infected dural cells were cocultured with osteoblasts using a transwell system for 7 days. Dural cells infected with null adenovirus served as the negative control. In separate cultures, osteoblasts were directly infected with the adenoviral-FGFR2 constructs. Osteoblast proliferation was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and differentiation was analyzed by alkaline phosphatase assay, histochemical staining, and gene expression studies. Osteoblasts directly infected with the Crouzon (C278F-FGFR2) mutation demonstrated an increase in cell proliferation (P < 0.05). Osteoblasts directly infected with the Apert (P253R-FGFR2) mutation demonstrated an increase in alkaline phosphatase activity. In coculture experiments, osteoblasts cocultured with Crouzon-transformed dural cells demonstrated increased cell proliferation (P < 0.05), whereas osteoblasts cocultured with Apert-transformed dural cells showed an increase in alkaline phosphatase activity (P < 0.05). In addition, osteogenic gene expression (alkaline phosphatase, osteopontin, and runx2) were up-regulated in osteoblasts cocultured with Apert-expressing dural cells. These experiments suggest that FGFR2 mutations in dural cells alter normal dural signaling. Apert mutations promote osteodifferentiation, whereas Crouzon mutations result in enhanced cell proliferation. These mutations may induce craniosynostosis in part through the influence of mutation-induced constitutive signaling in the dura, with subsequent enhancement of dural-mediated osteogenesis.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
D
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Alkaline Phosphatase,
http://linkedlifedata.com/resource/pubmed/chemical/Arginine,
http://linkedlifedata.com/resource/pubmed/chemical/Biological Markers,
http://linkedlifedata.com/resource/pubmed/chemical/Coloring Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Core Binding Factor Alpha 1 Subunit,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine,
http://linkedlifedata.com/resource/pubmed/chemical/Fgfr2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Osteopontin,
http://linkedlifedata.com/resource/pubmed/chemical/Phenylalanine,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Fibroblast Growth...,
http://linkedlifedata.com/resource/pubmed/chemical/Runx2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Spp1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Tetrazolium Salts,
http://linkedlifedata.com/resource/pubmed/chemical/Thiazoles,
http://linkedlifedata.com/resource/pubmed/chemical/thiazolyl blue
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Mar
|
| pubmed:issn |
1536-3732
|
| pubmed:author | |
| pubmed:issnType |
Electronic
|
| pubmed:volume |
21
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
462-7
|
| pubmed:meshHeading |
pubmed-meshheading:20489451-Acrocephalosyndactylia,
pubmed-meshheading:20489451-Adenoviridae,
pubmed-meshheading:20489451-Alkaline Phosphatase,
pubmed-meshheading:20489451-Animals,
pubmed-meshheading:20489451-Arginine,
pubmed-meshheading:20489451-Biological Markers,
pubmed-meshheading:20489451-Cell Differentiation,
pubmed-meshheading:20489451-Cell Proliferation,
pubmed-meshheading:20489451-Cells, Cultured,
pubmed-meshheading:20489451-Coculture Techniques,
pubmed-meshheading:20489451-Coloring Agents,
pubmed-meshheading:20489451-Core Binding Factor Alpha 1 Subunit,
pubmed-meshheading:20489451-Craniofacial Dysostosis,
pubmed-meshheading:20489451-Craniosynostoses,
pubmed-meshheading:20489451-Cysteine,
pubmed-meshheading:20489451-Dura Mater,
pubmed-meshheading:20489451-Genetic Vectors,
pubmed-meshheading:20489451-Mice,
pubmed-meshheading:20489451-Osteoblasts,
pubmed-meshheading:20489451-Osteogenesis,
pubmed-meshheading:20489451-Osteopontin,
pubmed-meshheading:20489451-Phenylalanine,
pubmed-meshheading:20489451-Point Mutation,
pubmed-meshheading:20489451-Receptor, Fibroblast Growth Factor, Type 2,
pubmed-meshheading:20489451-Syndrome,
pubmed-meshheading:20489451-Tetrazolium Salts,
pubmed-meshheading:20489451-Thiazoles
|
| pubmed:year |
2010
|
| pubmed:articleTitle |
Dura in the pathogenesis of syndromic craniosynostosis: fibroblast growth factor receptor 2 mutations in dural cells promote osteogenic proliferation and differentiation of osteoblasts.
|
| pubmed:affiliation |
Division of Plastic and Reconstructive Surgery, The Children's Hospital of Philadelphia and the Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA. Buang_78@yahoo.com
|
| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
|