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 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.
Center of Calcium and Bone Research (COCAB), Faculty of Science, Mahidol University, Bangkok, Thailand; Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand.
Narattaphol
N
Charoenphandhu
Kamonshanok
K
Kraidith
Jarinthorn
J
Teerapornpuntakit
Kanogwun
K
Thongchote
Pissared
P
Khuituan
Saovaros
S
Svasti
Nateetip
N
Krishnamra
D000818:Animals; D002117:Calcitriol / Q000008:administration & dosage / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D005260:Female; D007279:Injections, Subcutaneous; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects*; D017136:Ion Transport / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013329:Structure-Activity Relationship; D055544:beta-Globins / Q000172:deficiency* / Q000378:metabolism; D017086:beta-Thalassemia / Q000378:metabolism*
D055544:beta-Globins; D002117:Calcitriol; D002118:Calcium
Ussing chamber; divalent metal transporter (DMT)-1; duodenum; thalassemia; vitamin D