The objective of one of our projects is to determine the mechanism by which vitamin C (ascorbic acid) controls connective tissue metabolism. Previously we showed that decreased collagen synthesis in parietal bone and cartilage of scorbutic guinea pigs was directly related to the extent of weight loss during the third and fourth week of scurvy, rather than to defective proline hydroxylation. Our current studies show that synthesis of another major component of cartilage extrcellular matrix, proteoglycan, also is decreased and that synthesis of collagen and proteoglycans appears to be coordinately regulated. These, and other results, suggest that ascorbate deficiency indirectly produces these effects by inducing anorexia, which leads to a chronic fasting state. Acute fasting for 96 hr with ascorbate supplementation causes a similar coordinate reduction in collagen and proteoglycan production. Decreased collagen production in both bone and cartilage of acutely fasted and scorbutic animals is not due to an increase in degradation but to decreased synthesis caused mainly by a reduction in the levels of procollagen mRNAs. In a second study, we have found that in a nitroquinoline oxide transformant of Syrian hamster embryo fibroblasts (NQT-SHE), there is almost complete suppression of synthesis of type I procollagen, the major product of the parent cells. This suppression is correlated with the absence of mRNA for pro alpha 1 I collagen polypeptide. In addition, synthesis of two previously undescribed types of collagen is induced. Both of these molecules appear to have a procollagen type of structure. Each is composed of a single subunit with a pepsin-resistant helical region having a typical repeating glycyl tripeptide sequence susceptible to bacterial collagenase, plus pepsin-sensitive noncollagenous regions. Current efforts are aimed at characterizing these collagens.
