The in vitro production and activity of 24, 25-dihydroxycholecalciferol in cartilage and calvarium

Previously reported results from our laboratory have indicated that 24, 25-dihydroxycholecalciferol can be formed in vitro during incubations of cartilage tissue or cartilage cells with 25-hydroxycholecalcified. They have also demonstrated the high potency of this dihydroxymetabolite of vitamin D3 in stimulating in vitro the sulfate incorporation into proteoglycans of cartilage cells in culture and in decreasing in vitro the parathyroid hormone action on rat calvarium phosphatases activities. The present report shows that 24, 25-)OH)2 D3 can also be produced during rat calvarium incubations with 25-hydroxycholecalciferol and that therefore calvarium as well as cartilage might be both a site of formation and a site of action for 24, 25-(OH)2 D3. The review of recent experimental and clinical investigations strongly suggests that this metabolite has a physiological significance and may be specifically active on some parameters of bone mineralization. Further studies on the cartilage and calvarium abilities to convert 25-hydroxycholecalciferol into 24, 25-(OH)2 D3 shows that this transformation occurs in the mitochondrial fraction but that it does not seem modified by factors known to control the 25-hydroxycholecalciferol metabolism in the kidney. Finally the analysis of experimental and clinical results published so far does not yet bring enough information to understand the significance of this extrarenal metabolism of 25-hydroxycholecalciferol.