1,25-Dihydroxyvitamin D3-induced intestinal calcium transport is impaired in β-globin knockout thalassemic mice

Besides being a common haematological disorder caused by a reduction in -globin production, -thalassemia has been reported to impair body calcium homeostasis, leading to massive bone loss and increased fracture risk. Here, we demonstrated that heterozygous -globin knockout thalassemic mice had a lower rate of duodenal calcium absorption compared with the wild-type littermates, whereas the epithelial electrical parameters, including transepithelial resistance, were not affected, suggesting no change in the epithelial integrity and permeability. Daily subcutaneous injection of 1 mu gkg(-1) 1,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3] for 3days enhanced the duodenal calcium absorption in wild-type, but not in thalassemic mice. Although -thalassemia increased the mRNA level of divalent metal transporter-1, an iron transporter in the duodenum, it had no effect on the transcripts of ferroportin-1 or the principal calcium transporters. In conclusion, -thalassemia impaired the 1,25(OH)(2)D-3-dependent intestinal calcium absorption at the post-transcriptional level, which, in turn, contributed to the dysregulation of body calcium metabolism and -thalassemia-induced osteopenia. Copyright (c) 2013 John Wiley & Sons, Ltd.