Production of 1α,25-Dihydroxy-3-epi-vitamin D 3 in two rat osteosarcoma cell lines (UMR 106 and ROS 17/2.8): existence of the C-3 epimerization pathway in ROS 17/2.8 cells in which the C-24 oxidation pathway is not expressed

Abstract

The secosteroid hormone 1α,25-dihydroxyvitamin D 3 [1α,25(OH) 2D 3] is metabolized into calcitroic acid through the carbon 24 (C-24) oxidation pathway. It is now well established that the C-24 oxidation pathway plays an important role in the target tissue inactivation of 1α,25(OH) 2D 3. Recently, we reported that 1α,25(OH) 2D 3 is also metabolized into 1α,25-dihydroxy-3-epi-vitamin D 3 [1α,25(OH) 2-3-epi-D 3] through the carbon 3 (C-3) epimerization pathway in human keratinocytes, human colon carcinoma cells (Caco-2), and bovine parathyroid cells. In a previous study, it was demonstrated that 1α,25(OH) 2-3-epi-D 3 when compared to 1α,25(OH) 2D 3 was less active in stimulating intestinal calcium absorption, calcium mobilization from bone, and induction of calbindin D 28k. These findings suggest that the C-3 epimerization pathway, like the C-24 oxidation pathway, may play a role in the target tissue inactivation of 1α,25(OH) 2D 3. In this study, we determined the relationship between the C-24 oxidation and the C-3 epimerization pathways by investigating the metabolism of 1α,25(OH) 2D 3 in two rat osteosarcoma cell lines (UMR 106 and ROS 17/2.8). These two cell lines differ from each other in their ability to metabolize 1α,25(OH) 2D 3 through the C-24 oxidation pathway. It has been previously reported that the C-24 oxidation pathway is expressed only in UMR 106 cells but not in ROS 17/2.8 cells. The results of our present study provide new evidence that both cell lines possess the ability to metabolize 1α,25(OH) 2D 3 into 1α,25(OH) 2-3-epi-D 3 through the C-3 epimerization pathway. Our results also reconfirm the findings of previous studies indicating that UMR 106 cells are the only ones which express the C-24 oxidation pathway out of the two cell lines studied. Furthermore, this study reveals for the first time that the C-3 epimerization pathway may become an alternate metabolic pathway for the target tissue inactivation of 1α,25(OH) 2D 3 in some cells, such as ROS 17/2.8, in which the C-24 oxidation pathway is not expressed.