Expression patterns of chondrocyte genes cloned by differential display intibial dyschondroplasia

Tibial dyschondroplasia (TD) appears to involve a failure of the growth pla te chondrocytes within growing long bones to differentiate fully to the hyp ertrophic stage, resulting in a mass of prehypertrophic chondrocytes which form the avascular TD lesion. Many biochemical and molecular markers of cho ndrocyte hypertrophy are absent from the lesion, or show reduced expression , but the cause of the disorder remains to be identified. As differentiatio n to the hypertrophic state is impaired in TD, we hypothesised that chondro cyte genes that are differentially expressed in the growth plate should sho w altered expression in TD. Using differential display, four genes, B-cadhe rin, EF2, HT7 and Ex-FABP were cloned from chondrocytes stimulated to diffe rentiate to the hypertrophic stage in vitro, and their differential express ion confirmed in vivo. Using semi-quantitative RT-PCR, the expression patte rns of these genes were compared in chondrocytes from normal and TD growth plates. Surprisingly, none of these genes showed the pattern of expression that might be expected in TD lesion chondrocytes, and two of them, B-cadher in and Ex-FABP, were upregulated in the lesion. This indicates that the TD phenotype does not merely reflect the absence of hypertrophic marker genes, but may be influenced by more complex developmental mechanisms/defects tha n previously thought. (C) 2000 Elsevier Science B.V. All rights reserved.