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Alteration of vitamin D metabolic enzyme expression and calcium transporter abundance in kidney involved in type 1 diabetes-induced bone loss

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Abstract

Summary

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.

Introduction

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.

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Acknowledgments

This project was sponsored by Shanghai Pujiang Program (10PJ1407700) and Innovation Program of Shanghai Municipal Education Commission (11ZZ137) for Yan Zhang. HWD was partially supported by grants from NIH (P50AR055081, R01AG026564, R01AR050496, RC2DE020756, R01AR057049, and R03TW008221) and Franklin D. Dickson/Missouri Endowment.

Conflicts of interest

None.

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Authors and Affiliations

  1. 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

    Y. Zhang & H.-W. Deng

  2. School of Medicine, University of Missouri—Kansas City, Kansas City, MO, USA

    C. J. Papasian & H.-W. Deng

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  1. Y. Zhang
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  2. C. J. Papasian
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  3. H.-W. Deng
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Correspondence to Y. Zhang.

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Zhang, Y., Papasian, C.J. & Deng, HW. Alteration of vitamin D metabolic enzyme expression and calcium transporter abundance in kidney involved in type 1 diabetes-induced bone loss. Osteoporos Int 22, 1781–1788 (2011). https://doi.org/10.1007/s00198-010-1404-1

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  • DOI: https://doi.org/10.1007/s00198-010-1404-1

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