title: Human immortalized chondrocytes carrying heterozygous FGFR3 mutations: an in vitro model to study chondrodysplasias.
abstract: Achondroplasia and thanatophoric dysplasia are human chondrodysplasias caused by mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. We have developed an immortalized human chondrocyte culture model to study the regulation of chondrocyte functions. One control and eight mutant chondrocytic lines expressing different FGFR3 heterozygous mutations were obtained. FGFR3 signaling pathways were modified in the mutant lines as revealed by the constitutive activation of the STAT pathway and an increased level of P21(WAF1/CIP1) protein. This model will be useful for the study of FGFR3 function in cartilage studies and future therapeutic approaches in chondrodysplasias.
authors.affiliation: INSERM U781, Hôpital Necker-Enfants Malades, 149 rue de Sèvres, Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Benoist-Lasselin
authors.forename: Linda
authors.initials: L
authors.lastname: Gibbs
authors.forename: Solange
authors.initials: S
authors.lastname: Heuertz
authors.forename: Thierry
authors.initials: T
authors.lastname: Odent
authors.forename: Arnold
authors.initials: A
authors.lastname: Munnich
authors.forename: Laurence
authors.initials: L
authors.lastname: Legeai-Mallet
mesh_terms: D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D024043:Collagen Type II / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D015870:Gene Expression; D006579:Heterozygote; D006609:High Mobility Group Proteins / Q000235:genetics; D006801:Humans; D015151:Immunoblotting; D008856:Microscopy, Fluorescence; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009154:Mutation; D010009:Osteochondrodysplasias / Q000235:genetics / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055758:SOX9 Transcription Factor; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics
chemical_list: C493956:CDKN1A protein, human; C499177:COL2A1 protein, human; D024043:Collagen Type II; D050759:Cyclin-Dependent Kinase Inhibitor p21; D006609:High Mobility Group Proteins; D012333:RNA, Messenger; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; D050791:STAT Transcription Factors; D014157:Transcription Factors; C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3; D020928:Mitogen-Activated Protein Kinases