Identification and Characterization of a Unique Chondrocyte Gene Involved in Transition to Hypertrophy

Autor: Reynolds, Susan D., Johnston, Carl, Leboy, Phoebe S., O'Keefe, Regis J., Puzas, J.Edward, Rosier, Randy N., Reynolds, Paul R.
Zdroj: Experimental Cell Research; July 1996, Vol. 226 Issue: 1 p197-207, 11p
Abstrakt: The character of differentiating chondrocytes in growing long bones has been defined by altered expression of a limited number of genes. To expand this set we have applied differential display to identify genes expressed in either mineralizing or nonmineralizing chondrocytes. One such gene,Band 17,has the following characteristics: (1)Band 17expression is predominantly found in cartilage destined for mineralization.Band 17mRNA is undetectable in articular cartilage and undetectable or weak in all other tissues tested. (2)Band 17expression is spatially restricted to the lower proliferative/upper hypertrophic zone of chondrocytes in the growth plate of long bones and embryonic vertebrae. (3) Induction of a hypertrophic phenotype in progenitor sternal chondrocytes by treatment with ascorbate increases expression ofBand 17.(4) Induction of hypertrophy in growth plate chondrocytes in short-term monolayer cultures correlates with a rapid but transient rise inBand 17message. Our interpretation of these findings is thatBand 17expression is associated with the transition to hypertrophy, not maintenance of the hypertrophic phenotype. Molecular analysis of the 3′ end ofBand 17cDNAs and genomic structure has shown thatBand 17is a single copy gene transcribed into four messages. Alternative splicing of these messages is predicted to result in two proteins that differ at the C-terminal by 131 amino acids. The longer protein contains a C-terminal consensus sequence that potentially targets this protein to the lumen of the endoplasmic reticulum. There is aBand 17homologue in humans, suggesting conservation ofBand 17function in mammals. In summary, the pattern of expression and the predicted primary structure identifyBand 17as unique among all previously known chondrocyte genes.
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