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

ABSTRACT

Besides being a common haematological disorder caused by a reduction in ß-globin production, ß-thalassemia has been reported to impair body calcium homeostasis, leading to massive bone loss and increased fracture risk. Here, we demonstrated that heterozygous ß-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 µg kg(-1) 1,25-dihydroxyvitamin D3 [1,25(OH)2 D3 ] for 3 days enhanced the duodenal calcium absorption in wild-type, but not in thalassemic mice. Although ß-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, ß-thalassemia impaired the 1,25(OH)2 D3 -dependent intestinal calcium absorption at the post-transcriptional level, which, in turn, contributed to the dysregulation of body calcium metabolism and ß-thalassemia-induced osteopenia.