Alteration of vitamin D metabolic enzyme expression and calcium transporter abundance in kidney involved in type 1 diabetes-induced bone loss.
This study aimed to delineate the mechanism involved in type 1 diabetes-induced bone loss. The results revealed the alteration of vitamin D metabolic enzyme expression and the downregulation of renal calcium transporter abundance in type 1 diabetic mice.


BACKGROUND
The purpose of this study was to investigate the changes of the expression of vitamin D metabolic enzymes and transcellular calcium-transporting proteins in kidneys from mice with experimentally induced diabetes.


METHODS
Male DBA/2J mice were injected with either vehicle (control) or streptozotocin (STZ) daily for five consecutive days. Bone mineral density was measured by peripheral quantitative computerized tomography, and bone histomorphology was analyzed by Safranin O staining. Real-time PCR and Western blotting were applied to determine the expression of target genes and proteins.


RESULTS
Type 1 diabetes produced high urinary calcium excretion and loss of trabecular bone measured at the proximal metaphysis of the tibia and the distal femur. Bone loss was associated with deterioration of trabecular bone microstructure. Quantified PCR results showed that mRNA expression level in the kidney of diabetic mice for 25-hydroxyvitamin D-24-hydroxylase was downregulated at week 10, while those for 25-hydroxyvitamin D-1α-hydroxylase were upregulated at week 20. In addition, mRNA expression levels for renal transient receptor potential V6, plasma membrane Ca-ATPase (PMCA)1b, and vitamin D receptor (VDR) genes were decreased in STZ-treated mice. Western blot analysis showed that protein expression of PMCA1b and VDR was significantly decreased in kidneys from STZ-treated mice compared to that of controls.


CONCLUSIONS
The limitation in this study is the lack of vitamin D, parathyroid hormone, and phosphorus levels in serum. However, the present study supports the conclusion that the underlying mechanism contributing to type 1 diabetes-associated bone loss may be alterations of vitamin D metabolic enzyme expression and associated decreases in expression of renal calcium transporters.
Zhang
Y
Y
Center of System Biomedical Sciences, School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai 200093, People's Republic of China. medicineyan@yahoo.com.cn
Papasian
C J
CJ
Deng
H-W
HW
D000419:Albuminuria / Q000209:etiology / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002118:Calcium / Q000097:blood / Q000652:urine; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D005269:Femur / Q000503:physiopathology; D005786:Gene Expression Regulation; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D010024:Osteoporosis / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D012333:RNA, Messenger / Q000235:genetics; D013250:Steroid Hydroxylases / Q000235:genetics / Q000378:metabolism*; D013977:Tibia / Q000473:pathology / Q000503:physiopathology; D065668:Vitamin D3 24-Hydroxylase
D001786:Blood Glucose; D012333:RNA, Messenger; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase; D002118:Calcium