ECTS Abstracts (2015) 1 P90

The effects of long-term adult vitamin D deficiency on the regulation of CYP27B1 in mouse bone

Karen van der Meijden1,2, Joost Buskermolen1,2, Teun Schuurman3, Wilma Steegenga3, Elske Brouwer-Brolsma3, Leo van Ruijven2,4, Paul Lips1,2 & Nathalie Bravenboer1,2

1VU University Medical Center, Amsterdam, The Netherlands; 2MOVE Research Institute, Amsterdam, The Netherlands; 3Wageningen University, Wageningen, The Netherlands; 4Academic Centre for Dentistry Amsterdam, Amsterdam, The Netherlands.

Vitamin D deficiency, a common condition in the elderly population, causes a decrease of calcium absorption from the intestine and secondary hyperparathyroidism which leads to bone loss, osteoporosis and mineralisation defects in the long term. Long-term vitamin D deficiency may also affect the regulation of the 1α-hydroxylase gene CYP27B1 in bone, since bone cells are able to synthesise 1,25-dihydroxyvitamin D3 needed for stimulation of osteoblast differentiation and mineralisation. Therefore, the aim of this study is to determine the effects of long-term adult vitamin D deficiency on bone mineral density and the regulation of CYP27B1 in mouse bone. Ten-month-old male mice were fed a diet containing 0.5% calcium and 0 (n=8) or 1 (n=9) IU/gram vitamin D3 for 14 months. At an age of 24 months, the mice were sacrificed for mRNA analysis of CYP27B1, CYP24 and VDR from tibiae and kidneys using RT-PCR and for micro-computed tomography analysis of the humeri. Plasma 25-hydroxyvitamin D3 (25(OH)D3) levels were measured using liquid chromatography-tandem mass spectrometry. Mean 25(OH)D3 plasma levels were <4 nmol/L in the vitamin D deficient mice and 57.4 nmol/L in the control mice. Bone mineral density was not different between the vitamin D deficient and control mice. Moreover, the humeral cortices showed similar patterns of bone mineral density in both groups. CYP27B1 and VDR mRNA levels in bone and kidney did not show differences between the vitamin D deficient and control mice. Kidney CYP24 mRNA levels were similar in both groups, while bone CYP24 mRNA levels were not expressed. In conclusion, the diet contained probably sufficient calcium to maintain an adequate bone mineralization degree after long-term vitamin D deficiency. Interestingly, although plasma 25(OH)D3 levels were very low and thus almost no substrate was present, bone cells continued to express CYP27B1 at the same level.

Disclosure: The authors declared no competing interests.

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