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In vitro studies on clonal growth of chondrocytes in thanatophoric dysplasia

Journal Article · · American Journal of Medical Genetics
;  [1];  [2]
  1. Univ. of Bonn (Germany)
  2. Univ. of Ulm (Germany); and others

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 of 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. 22 refs., 6 tabs.

OSTI ID:
539195
Journal Information:
American Journal of Medical Genetics, Journal Name: American Journal of Medical Genetics Journal Issue: 2 Vol. 63; ISSN 0148-7299; ISSN AJMGDA
Country of Publication:
United States
Language:
English

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