Regulation of collagen synthesis in fetal rat calvaria by 1,25-dihydroxyvitamin D3.
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.
D000818:Animals; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D002117:Calcitriol / Q000494:pharmacology*; D003094:Collagen / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D005333:Fetus; D007700:Kinetics; D011247:Pregnancy; D011347:Procollagen / Q000096:biosynthesis; D014176:Protein Biosynthesis / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D011347:Procollagen; D003094:Collagen; D002117:Calcitriol