1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3) inhibited
type I collagen synthesis in the central bone but not the periosteum of fetal rat calvaria maintained in organ culture. The central bone synthesized primarily
type I collagen, whereas the periosteum synthesized both types I and III
collagen. Enhanced degradation of newly synthesized
collagen seemed an unlikely mechanism for the observed decrease in
collagen synthesis since 1,25-(OH)2D3 reduced both the labeling of intracellular
procollagen and total [3H]
hydroxyproline formation in fetal rat calvaria. As measured by cell-free translation of
RNA extracted from calvaria, 1,25-(OH)2D3 decreased the level of functional
procollagen mRNA and
collagen synthesis to the same extent. Both
collagen synthesis and
procollagen mRNA levels were decreased as early as 3 h after exposure to 1,25-(OH)2D3 and were 50% of the control level by 24 hr. Upon removal of 1,25-(OH)2D3 from the cultures,
collagen synthesis and
procollagen mRNA remained depressed for 24 h but returned to control levels by 48 h. A reduction in
collagen synthesis and
procollagen mRNA was also observed in calvaria excised from 6-day-old rat pups given a single
subcutaneous injection of 1,25-(OH)2D3 (1.6 ng/g
body weight). We conclude that 1,25-(OH)2D3 inhibits the synthesis of
type I collagen in the differentiated osteoblast by reducing the level of functional
procollagen mRNA.