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

Abstract

Besides being a common haematological disorder caused by a reduction in β-globin production, β-thalassemia has been reported to impair body calcium homeostasis, leading to massive bone loss and increased fracture risk. Here, we demonstrated that heterozygous β-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 β-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, β-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 β-thalassemia-induced osteopenia.