REGULATION AND PROPERTIES OF BONE ALKALINE-PHOSPHATASE DURING VITAMIN-C-DEFICIENCY IN GUINEA-PIGS

The precise physiological role of alkaline phosphatase is unknown, alt hough evidence suggests it is involved in bone mineralization. Previou s studies showed that serum and bone alkaline phosphatase activity is decreased during vitamin C deficiency. Some effects of scurvy, such as inhibition of collagen synthesis, are related to weight loss and subs equent induction of insulin-like growth factor binding proteins and th ey can be duplicated in fasted guinea pigs receiving vitamin C, We fou nd that decreased alkaline phosphatase activity in bone and serum duri ng scurvy was not completely due to the ''fasting effect'' and that th e decrease in serum was due to loss of bone isoenzyme activity, There also was a decrease in immunoreactive enzyme protein and alkaline phos phatase mRNA concentrations in bone of scorbutic animals, indicating t hat synthesis of the enzyme was inhibited, Sialylation and addition of the glycosylphosphatidylinositol anchor to the enzyme in bone tissue were not affected by scurvy, The concentration of mRNA for osteocalcin , a bone-specific marker, also fell during scurvy and to a much greate r extent than either alkaline phosphatase or type I collagen mRNAs, wh ile osteopontin mRNA concentrations increased. These results differ fr om the reported role of ascorbic acid on the pattern of expression of these proteins during differentiation of osteoblasts in culture. The d ecreased expression of collagen, alkaline phosphatase, and osteocalcin could explain the defects in bone caused by scurvy. (C) 1996 Academic Press, Inc.