Expression patterns of chondrocyte genes cloned by differential display in tibial dyschondroplasia.
Tibial dyschondroplasia (TD) appears to involve a failure of the growth plate chondrocytes within growing long bones to differentiate fully to the hypertrophic stage, resulting in a mass of prehypertrophic chondrocytes which form the avascular TD lesion. Many biochemical and molecular markers of chondrocyte hypertrophy are absent from the lesion, or show reduced expression, but the cause of the disorder remains to be identified. As differentiation to the hypertrophic state is impaired in TD, we hypothesised that chondrocyte genes that are differentially expressed in the growth plate should show altered expression in TD. Using differential display, four genes, B-cadherin, EF2, HT7 and Ex-FABP were cloned from chondrocytes stimulated to differentiate to the hypertrophic stage in vitro, and their differential expression confirmed in vivo. Using semi-quantitative RT-PCR, the expression patterns 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-cadherin 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 than previously thought.
Jefferies
D
D
Bone Biology Group, Division of Integrative Biology, Roslin Institute (Edinburgh), Roslin, EH25 9PS, Midlothian, UK. david.jeffries@bbsrc.ac.uk
Houston
B
B
Lester
D
D
Whitehead
C C
CC
Thorp
B H
BH
Botman
M
M
Farquharson
C
C
D000818:Animals; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D030161:Avian Proteins; D051926:Basigin; D001798:Blood Proteins; D015820:Cadherins / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D002478:Cells, Cultured; D002645:Chickens; D019902:Chondrocytes / Q000378:metabolism*; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics; D050556:Fatty Acid-Binding Proteins; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D006132:Growth Plate / Q000254:growth & development / Q000378:metabolism; D024002:HMGB Proteins; D054834:Lipocalins; D008562:Membrane Glycoproteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D010009:Osteochondrodysplasias / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055748:SOXB1 Transcription Factors; D013977:Tibia / Q000254:growth & development / Q000378:metabolism*; D014157:Transcription Factors
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D030161:Avian Proteins; D001798:Blood Proteins; C102624:Bsg protein, Gallus gallus; C079432:Bsg protein, rat; D015820:Cadherins; D002352:Carrier Proteins; C066299:Ch21 protein, chicken; D004268:DNA-Binding Proteins; D050556:Fatty Acid-Binding Proteins; D024002:HMGB Proteins; D054834:Lipocalins; D008562:Membrane Glycoproteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D055748:SOXB1 Transcription Factors; C527784:Sox2 protein, rat; D014157:Transcription Factors; D051926:Basigin