Ukr.Biochem.J. 2018; Volume 90, Issue 2, Mar-Apr, pp. 56-65

doi: https://doi.org/10.15407/ubj90.02.056

Osteoprotective effects of vitamin D(3) in diabetic mice is VDR-mediated and regulated via RANKL/RANK/OPG axis

D. O. Labudzynskyi, І. О. Shymanskyi, O. O. Lisakovska, М. М. Veliky

Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: konsumemt3@gmail.com

There is growing evidence that vitamin D3 deficiency could be a contributing factor in the development of different chronic diseases and their complications. A better understanding of how diabetes influences bone tissue metabolism may become an underlying basis for effective prevention and treatment of skeletal disorders in diabetes. This study was performed to define diabetes-associated impairments in bone tissue remodeling in relation to vitamin D bioavailability and to estimate the effects of cholecalciferol treatment. We established that chronic hyperglycemia in diabetes was accompanied by a 2.15-fold decrease of 25OHD content in the serum. Vitamin D deficiency correlated with impairments of tibia biomechanical properties (decline of bone maximal load and stiffness values). µCT analysis of tibia showed respectively 3.0-, 2.1- and 1.3-fold decreases in trabecular bone volume per tissue volume, trabecular number and cortical thickness in diabetes indicating the development of secondary osteoporosis. Diabetes led to up-regulation of NF-κB/phosho-p65, RANKL, RANK (2.3-, 1.51-, 1.72-fold respectively) and down-regulation of OC, OPG and VDR (1.5-, 1.6- and 1.8-fold respectively) in tibial tissue of diabetic mice. Diabetes-associated abnormalities in the serum levels of RANKL, OPG and TRAP were also detected. Restoration of circulatory 25OHD content was achieved due to cholecalciferol treatment. Better vitamin D availability and increased VDR expression resulted in normalization of RANKL/RANK/OPG- and NF-κB-associated pathways that attenuated diabetes-induced structural and biomechanical abnormalities in bone tissue.

Keywords: , , , ,


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