title: In vitro studies on clonal growth of chondrocytes in thanatophoric dysplasia.
abstract: Thanatophoric dysplasia (TD) is characterized by a disorganized growth plate with markedly reduced proliferative and hypertrophic cartilage zones. Therefore, we studied in vitro the proliferation rates of articular chondrocytes from five TD patients and age-matched controls in response to bFGF, IGF-I, IGF-II, and TGF-beta 1. In human fetal controls bFGF was the most potent growth factor. Clonal growth the articular chondrocytes in response to bFGF was reduced in two of five TD patients and slightly below the range of controls in a third case. Stimulation of chondrocyte proliferation by IGF I and II was reduced in the patient whose response to bFGF was most markedly impaired. The effect of TGF-beta 1 ranged from normal to slightly elevated values in TD fetuses. These results indicate heterogeneity of the underlying defects in TD. Low proliferative responses of chondrocytes to bFGF and IGF-I/II are likely to play a key role in the pathogenesis of some cases. In two of five patients studied, the mechanisms of bFGF and IGF-signal transduction are candidates for the primary molecular defect.
authors.affiliation: Department of Neonatology, University of Bonn, Germany.
authors.forename: R E
authors.initials: RE
authors.lastname: Brenner
authors.forename: A
authors.initials: A
authors.lastname: Nerlich
authors.forename: R
authors.initials: R
authors.lastname: Terinde
authors.forename: P
authors.initials: P
authors.lastname: Bartmann
mesh_terms: D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects / Q000254:growth & development*; D002455:Cell Division; D002478:Cells, Cultured; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology; D013796:Thanatophoric Dysplasia / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II