Developmental regulation of creatine kinase activity in cells of the epiphyseal growth cartilage.
During the process of endochondral bone formation, the maturing chondrocyte exhibits profound changes in energy metabolism. To explore the mechanism of energy conservation in cartilage we examined the expression of creatine kinase, an enzyme that catalyzes the formation of ATP in tissues under oxygen stress. Measurement of creatine kinase activity and cytochemical assessment of enzyme distribution clearly showed that the level of enzyme activity was related to chondrocyte maturation. Thus, as the cells hypertrophied, there was a progressive increase in creatine kinase activity. Similarly, an elevation in creatine kinase activity was noted in chondrocyte cultures as the cells assumed an hypertrophic state. When cartilage calcification was disturbed by rickets, there was a decrease in enzyme activity in the hypertrophic region. Studies were performed to examine the creatine kinase isozyme profile of cells of the epiphysis. In resting and proliferating cartilage, the isoform was MM. In hypertrophic cartilage, the predominant isoforms were MB and BB. In terms of the creatine phosphate content, the highest values were seen in the proliferative region; lower amounts were present in hypertrophic and resting cartilage; and no creatine phosphate was detected in calcified cartilage. These data suggest that turnover of creatine phosphate is greatest in the mineralized region of the epiphysis. The results of these investigations point to creatine kinase as being under developmental control. The activity of the enzyme in cartilage cells should serve as a marker of developmental events associated with chondrocyte proliferation, hypertrophy, and mineralization.
Shapiro
I M
IM
Department of Biochemistry, School of Dental Medicine, University of Pennsylvania, Philadelphia.
Debolt
K
K
Funanage
V L
VL
Smith
S M
SM
Tuan
R S
RS
D000818:Animals; D002356:Cartilage / Q000166:cytology / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D002645:Chickens; D003402:Creatine Kinase / Q000378:metabolism*; D004734:Energy Metabolism; D006132:Growth Plate / Q000166:cytology / Q000201:enzymology* / Q000254:growth & development / Q000473:pathology; D006651:Histocytochemistry; D006984:Hypertrophy / Q000201:enzymology; D007527:Isoenzymes / Q000378:metabolism; D008903:Minerals / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism
D007527:Isoenzymes; D008903:Minerals; D010725:Phosphocreatine; D003402:Creatine Kinase